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Phosphodiesterase inhibitors elevate the levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate, which have been associated with various anti-inflammatory effects that can help alleviate asthma symptoms. This study aims to assess the impact of Tadalafil, a selective phosphodiesterase inhibitor, on pulmory function in patients with asthma. This study was a randomized, double-blind clinical trial conducted in 2021 at Imam Khomeini Hospital in Ahvaz, Iran. The study enrolled 44 patients with severe asthma, who were divided equally into a Tadalafil group and a placebo group. The Tadalafil group received 20 mg/day of Tadalafil, while the placebo group received a placebo at the same dose. The patients’ spirometry tests, asthma quality of life questionire, 6-minute walking distance, and quality of life were measured at the beginning of the study and one month later. The study results indicated that there was no statistically significant difference between the Tadalafil group and the placebo group in terms of pulmory parameters (p>0.05). Furthermore, the scores for patients’ quality of life (p=0.167) and the 6-minute walking test (p=0.148) at the end of the study did not show any statistically significant improvement compared to the placebo group. Results showed that the use of Tadalafil (20 mg) once daily for one month in patients with severe asthma did not affect clinical and laboratory outcomes.

RNA therapeutics, such as mRNA, siRNA, and CRISPR–Cas9, present exciting avenues for treating diverse diseases. However, their potential is commonly hindered by vulnerability to degradation and poor cellular uptake, requiring effective delivery systems. Lipid nanoparticles (LNPs) have emerged as a leading choice for in vivo RNA delivery, offering protection against degradation, enhanced cellular uptake, and facilitation of endosomal escape. However, LNPs encounter numerous challenges for targeted RNA delivery in vivo, demanding advanced particle engineering, surface functionalization with targeting ligands, and a profound comprehension of the biological milieu in which they function. This review explores the structural and physicochemical characteristics of LNPs, in-vivo fate, and customization for RNA therapeutics. We highlight the quality-by-design (QbD) approach for targeted delivery beyond the liver, focusing on biodistribution, immunogenicity, and toxicity. In addition, we explored the current challenges and strategies associated with LNPs for in-vivo RNA delivery, such as ensuring repeated-dose efficacy, safety, and tissue-specific gene delivery. Furthermore, we provide insights into the current clinical applications in various classes of diseases and finally prospects of LNPs in RNA therapeutics. Graphical Abstract

Mechanically activated (MA) ion channels convert physical forces into electrical signals, and are essential for eukaryotic physiology. Despite their importance, few bona-fide MA channels have been described in plants and animals. Here, we show that various members of the OSCA and TMEM63 family of proteins from plants, flies, and mammals confer mechanosensitivity to naïve cells. We conclusively demonstrate that OSCA1.2, one of the Arabidopsis thaliana OSCA proteins, is an inherently mechanosensitive, pore-forming ion channel. Our results suggest that OSCA/TMEM63 proteins are the largest family of MA ion channels identified, and are conserved across eukaryotes. Our findings will enable studies to gain deep insight into molecular mechanisms of MA channel gating, and will facilitate a better understanding of mechanosensory processes in vivo across plants and animals.

In response to touch, some carnivorous plants such as the Venus flytrap have evolved spectacular movements to capture animals for nutrient acquisition. However, the molecules that confer this sensitivity remain unknown. We used comparative transcriptomics to show that expression of three genes encoding homologs of the MscS-Like (MSL) and OSCA/TMEM63 family of mechanosensitive ion channels are localized to touch-sensitive trigger hairs of Venus flytrap. We focus here on the candidate with the most enriched expression in trigger hairs, the MSL homolog FLYCATCHER1 (FLYC1). We show that FLYC1 transcripts are localized to mechanosensory cells within the trigger hair, transfecting FLYC1 induces chloride-permeable stretch-activated currents in naïve cells, and transcripts coding for FLYC1 homologs are expressed in touch-sensing cells of Cape sundew, a related carnivorous plant of the Droseraceae family. Our data suggest that the mechanism of prey recognition in carnivorous Droseraceae evolved by co-opting ancestral mechanosensitive ion channels to sense touch.

There has been increasing attention to produce porous scaffolds that mimic human bone properties for enhancement of tissue ingrowth, regeneration, and integration. Additive manufacturing (AM) technologies, i.e., three dimensional (3D) printing, have played a substantial role in engineering porous scaffolds for clinical applications owing to their high level of design and fabrication flexibility. To this end, this review article attempts to provide a detailed overview on the main design considerations of porous scaffolds such as permeability, adhesion, vascularisation, and interfacial features and their interplay to affect bone regeneration and osseointegration. Physiology of bone regeneration was initially explained that was followed by analysing the impacts of porosity, pore size, permeability and surface chemistry of porous scaffolds on bone regeneration in defects. Importantly, major 3D printing methods employed for fabrication of porous bone substitutes were also discussed. Advancements of MA technologies have allowed for the production of bone scaffolds with complex geometries in polymers, composites and metals with well-tailored architectural, mechanical, and mass transport features. In this way, a particular attention was devoted to reviewing 3D printed scaffolds with triply periodic minimal surface (TPMS) geometries that mimic the hierarchical structure of human bones. In overall, this review enlighten a design pathway to produce patient-specific 3D-printed bone substitutions with high regeneration and osseointegration capacity for repairing large bone defects.

Metabolic syndrome (MetS) is defined as a disorder with multiple abnormalities, including obesity, high blood pressure, dyslipidemia, and high blood glucose. MetS is the best-known risk factor for type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and obesity. With the globally increasing prevalence of MetS and its related abnormalities, attention to safe and effective prevention and treatment of this complex disorder has been increased. In particular, most treatments have been devoted to using natural agents that could provide more reliable and effective medicinal products with fewer side effects. L. (purslane) is an herb whose therapeutic properties could be found in some ancient medical books. Purslane has shown analgesic, antispasmodic, skeletal muscle relaxant, bronchodilator, antiasthmatic, anti-inflammatory, antiseptic, diuretic, antibacterial, antipyretic, and wound-healing properties. In addition, purslane's hypoglycemic and hypolipidemic properties have been reported in different studies. The positive effects of this plant include reducing stress oxidative and inflammation along with the atherogenic index, improving insulin level and glucose uptake, decreasing lipid profiles, and ameliorating weight gain. These activities could reduce MetS complications. This review aims to provide a comprehensive overview of various , animal, and human studies regarding the effect of on metabolic syndrome to better understand the underlying mechanisms of action for designing more effective treatments.

Due to the growing populations in areas at high risk of natural disasters, hazard and risk assessments of landslides have attracted significant attention from researchers worldwide. In order to assess potential risks and design possible countermeasures, it is necessary to have a better understanding of this phenomenon and its mechanism. As a result, the prediction of landslide evolution using continuum dynamic modeling implemented in advanced simulation tools is becoming more important. We analyzed a depth-integrated, two-phase model implemented in two different sets of code to stimulate rapid landslides, such as debris flows and rock avalanches. The first set of code, r.avaflow, represents a GIS-based computational framework and employs the NOC-TVD numerical scheme. The second set of code, GeoFlow-SPH, is based on the mesh-free numerical method of smoothed particle hydrodynamics (SPH) with the capability of describing pore pressure’s evolution along the vertical distribution of flowing mass. Two real cases of an Acheron rock avalanche and Sham Tseng San Tsuen debris flow were used with the best fit values of geotechnical parameters obtained in the prior modeling to investigate the capabilities of the sets of code. Comparison of the results evidenced that both sets of code were capable of properly reproducing the run-out distance, deposition thickness, and deposition shape in the benchmark exercises. However, the values of maximum propagation velocities and thickness were considerably different, suggesting that using more than one set of simulation code allows us to predict more accurately the possible scenarios and design more effective countermeasures.

Objectives: Enlarged adenoids can lead to obstruction of the nasopharyngeal airway and subsequent oral respiration. Oral breathing can cause dry mouth, dehydration in gingival tissue, and resistance to plaque accumulation. This study aimed to evaluate the impact of tonsillectomy on oral health status, salivary pH and flow rate, and common complications caused by tonsillar hypertrophy in children. Materials and Methods: An analytical before-and-after study was conducted on 60 children aged 5-12 years who required tonsillectomy. We gathered data through a questionnaire and collected unstimulated saliva using the spitting method for five minutes. Salivary pH was measured by a pH meter and its volume was determined with a calibrated test tube. The plaque index, bleeding index and modified gingival index were determined using a disclosing tablet, Williams’ probe and observational examination, respectively. All measurements were repeated one month after tonsillectomy. Paired t-test was used for data analysis. Results: We found a significant increase in mean pH and salivary flow rate after tonsillectomy and observed a decrease in oral health indices among the children one month after surgery. Over half of the children who reported complications such as dry mouth, itchy nose and throat, snoring, night sweats, and sleep disturbances experienced complete recovery after tonsillectomy. Conclusion: Based on the results obtained in the present study, children with enlarged adenoids showed significant improvements in salivary pH, salivary flow rate, and oral health indices, one month after tonsillectomy.

Celiac disease (CD) is one of the most common chronic diseases. Celiac disease has been associated with several autoimmune disorders, but the association with systemic lupus erythematosus (SLE) as a systemic autoimmune disease is still controversial. In this study, we aimed to determine the prevalence of biopsy-proven CD in patients with SLE, and to determine the clinical symptoms and laboratory data in these patients. In a cross-sectional study, SLE patients at a referral clinic were evaluated for gastrointestinal symptoms between March and December 2016. Patients were evaluated by a gastroenterologist, and upper gastrointestinal endoscopy with intestinal biopsy was performed if deemed necessary. The clinical symptoms, laboratory data, and endoscopy results were recorded and compared between groups. In total, 130 patients were evaluated in this study. Gastrointestinal symptoms were present in 40% of the patients. Endoscopy was performed in all SLE patients with gastrointestinal symptoms. Four patients (3%) were diagnosed as having CD based on biopsy results and response to a gluten-free diet. Anti-endomysium antibody (AEA) was found to be 100% sensitive and 99.2% specific for the diagnosis of CD in SLE patients, and anti-gliadin antibody (AGA) had a 50% sensitivity and 98% specificity. Patients with comorbid CD and SLE were significantly more likely to have diarrhea, abdominal pain, nausea/vomiting, recurrent oral aphthosis, and anemia. The results of this study suggest that a significant association is present between CD and SLE. We found a prevalence of 3% for biopsy-proven CD in patients with SLE, which is five times the prevalence of CD in the general population.