An electrochemical, and surface studies of synthesized Gemini ionic liquid as corrosion inhibitor for carbon steel in petroleum field.

In this work, we study the efficiency of N1, N3-dibenzyl-N1, N1, N3, N3-tetramethylpropane-1,3-diaminium chloride, as anticorrosion. This compound exhibits potential as a prospective remedy to stop the deterioration of carbon steel caused by corrosion in 1.0 M HCl. The synthesis of this compound is described in a comprehensive manner, and its composition is supported by a range of precise analytical approaches such as elemental analysis, and mass spectroscopy. Based on the findings of the investigation, the synthesized Gemini ionic liquid demonstrates a robust capacity to slow down the rate at which the metal corrodes. The Prepared compound was evaluation by electrochemical and morphology study. Our results revealed that elevating the inhibitor concentration led to an augmentation in inhibition effectiveness, reaching up to 94.8% at 200 ppm of the synthesized compound at 298 K. It is crucial to emphasize that the recently prepared Gemini ionic liquid is consistent with the Langmuir adsorption model and function as a mixed inhibitor, participating in the physio-chemisorption process of adsorption.

Tuning into miRNAs: A comprehensive analysis of their impact on diagnosis, and progression in asthma.

Asthma is a diverse inflammatory illness affecting the respiratory passages, leading to breathing challenges, bouts of coughing and wheezing, and, in severe instances, significant deterioration in quality of life. Epigenetic regulation, which involves the control of gene expression through processes such as post-transcriptional modulation of microRNAs (miRNAs), plays a role in the evolution of various asthma subtypes. In immune-mediated diseases, miRNAs play a regulatory role in the behavior of cells that form the airway structure and those responsible for defense mechanisms in the bronchi and lungs. They control various cellular processes such as survival, growth, proliferation, and the production of chemokines and immune mediators. miRNAs possess chemical and biological characteristics that qualify them as suitable biomarkers for diseases. They allow for the categorization of patients to optimize drug selection, thus streamlining clinical management and decreasing both the economic burden and the necessity for critical care related to the disease. This study provides a concise overview of the functions of miRNAs in asthma and elucidates their regulatory effects on the underlying processes of the disease. We provide a detailed account of the present status of miRNAs as biomarkers for categorizing asthma, identifying specific asthma subtypes, and selecting appropriate treatment options.

The emerging role of miRNAs in epilepsy: From molecular signatures to diagnostic potential.

Epilepsy is a medical condition characterized by intermittent seizures accompanied by changes in consciousness. Epilepsy significantly impairs the daily functioning and overall well-being of affected individuals. Epilepsy is a chronic neurological disorder characterized by recurrent seizures resulting from various dysfunctions in brain activity. The molecular processes underlying changes in neuronal structure, impaired apoptotic responses in neurons, and disruption of regenerative pathways in glial cells in epilepsy remain unknown. MicroRNAs (miRNAs) play a crucial role in regulating apoptosis, autophagy, oxidative stress, neuroinflammation, and the body's regenerative and immune responses. miRNAs have been shown to influence many pathogenic processes in epilepsy including inflammatory responses, neuronal necrosis and apoptosis, dendritic growth, synaptic remodeling, and other processes related to the development of epilepsy. Therefore, the purpose of our current analysis was to determine the role of miRNAs in the etiology and progression of epilepsy. Furthermore, they have been examined for their potential application as biomarkers and therapeutic targets.

Empagliflozin protects against isoprenaline-induced fibrosis in rat heart through modulation of TGF-ß/SMAD pathway.

AIM: Cardiac fibrosis is characterized by excessive accumulation of fibrous tissue, particularly collagens, in the myocardium. Accumulated fibrous tissue renders myocardium stiffer and reduces its contractility. Empagliflozin is an oral hypoglycemic agent with extra-diabetic functional profile toward maintaining cardiac functions. The present study aimed to examine protective effect of empagliflozin against an in-vivo model of cardiac fibrosis induced by isoprenaline and targeting TGF-ß/SMAD signaling as a possible pathway responsible for such effect. MAIN METHODS: Sixty animals were divided into six groups; the first was normal, and the second was treated with isoprenaline only (5 mg/kg/day I.P.) as a control. The third received pirfenidone (500 mg/kg/day P.O.), and the remaining groups received graded doses (5, 10, 20 mg/kg respectively) of empagliflozin for 14 days before fibrosis induction by isoprenaline (5 mg/kg/day) for 30 days. KEY FINDINGS: Isoprenaline increased cardiac enzymes, and cardiac tissues revealed elevated concentrations of transforming growth factor ß (TGF-ß1), monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor α (TNF-α), and c-jun N-terminal kinase (JNK) proteins. Expression of nuclear factor kappa B (NF-κB), alpha smooth muscle actin (α-SMA), collagens, suppressor of mothers against decapentaplegic (SMADs), connective tissue growth factor (CTGF), and fibronectin was upregulated. Empagliflozin improved the histological picture of heart tissue in comparison to fibrosis developed in controls, and protected against fibrosis through significant modulation of all mentioned parameters' concentrations and expressions. SIGNIFICANCE: Empagliflozin demonstrated a promising protective approach against biological model of cardiac fibrosis through an anti-fibrotic effect through targeting TGF-ß signaling pathways.

Harnessing the power of miRNAs: The molecular architects of asthma pathogenesis and potential targets for therapeutic innovation.

Asthma is a chronic non-communicable respiratory disease that is characterized by airway inflammation and hyperreactivity. Defective functions of airway smooth muscle and dysregulated signaling pathways play a crucial role in the pathogenesis of asthma. Anti-inflammatories and targeted therapy are mainly used for the treatment of asthma. Recent studies have investigated the role of non-coding RNAs, especially microRNAs (miRNAs; miR) in regulating gene expression and their involvement in the dysfunctional signaling pathways. In immune-mediated diseases, including asthma, miRNAs govern the actions of cells that form the airway structure and those responsible for the defense mechanisms in the bronchi and lungs. miRNAs control cell survival, proliferation, and growth, as well as the cells' capacity to produce and release chemokines and immune mediators. Moreover, miRNAs have an important role in the response to therapeutic interventions. Collectively, this review highlights the regulatory roles of miRNAs in modulating the different signaling pathways and therapeutic responses in asthma. Patients who suffer from asthma, particularly those with severe disease characteristics, may benefit from the prospective treatment options that include targeting miRNAs in order to reduce airway inflammation, hyperreactivity, and mucus production.

Decoding the role of miRNAs in oral cancer pathogenesis: A focus on signaling pathways.

Oral cancer (OC) is the predominant type originating in the head and neck region. The incidence of OC is mostly associated with behavioral risk factors, including tobacco smoking and excessive alcohol intake. Additionally, there is a lower but still significant association with viral infections such as human papillomaviruses and Epstein-Barr viruses. Furthermore, it has been observed that heritable genetic variables are linked to the risk of OC, in addition to the previously mentioned acquired risk factors. The current absence of biomarkers for OC diagnosis contributes to the frequent occurrence of advanced-stage diagnoses among patients. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs, and circular RNAs, have been observed to exert a significant effect on the transcriptional control of target genes involved in cancer, either through direct or indirect mechanisms. miRNAs are a class of short ncRNAs that play a role in regulating gene expression by enabling mRNA degradation or translational repression at the post-transcriptional phase. miRNAs are known to play a fundamental role in the development of cancer and the regulation of oncogenic cell processes. Notch signaling, PTEN/Akt/mTOR axis, KRAS mutation, JAK/STAT signaling, P53, EGFR, and the VEGFs have all been linked to OC, and miRNAs have been shown to have a role in all of these. The dysregulation of miRNA has been identified in cases of OC and is linked with prognosis.

Niosomal formulation of mefenamic acid for enhanced cancer targeting; preparation, characterization and biodistribution study using radiolabeling technique.

BACKGROUND: This work aimed to prepare niosomal formulations of an anticancer agent [mefenamic acid (MEF)] to enhance its cancer targeting. 131I was utilized as a radiolabeling isotope to study the radio-kinetics of MEF niosomes. METHODS: niosomal formulations were prepared by the ether injection method and assessed for entrapment efficiency (EE%), zeta potential (ZP), polydispersity index (PDI) and particle size (PS). MEF was labeled with 131I by direct electrophilic substitution reaction through optimization of radiolabeling-related parameters. In the radio-kinetic study, the optimal 131I-MEF niosomal formula was administered intravenously (I.V.) to solid tumor-bearing mice and compared to I.V. 131I-MEF solution as a control. RESULTS: the average PS and ZP values of the optimal formulation were 247.23 ± 2.32 nm and - 28.3 ± 1.21, respectively. The highest 131I-MEF labeling yield was 98.7 ± 0.8%. The biodistribution study revealed that the highest tumor uptake of 131I-MEF niosomal formula and 131I-MEF solution at 60 min post-injection were 2.73 and 1.94% ID/g, respectively. CONCLUSION: MEF-loaded niosomes could be a hopeful candidate in cancer treatment due to their potent tumor uptake. Such high targeting was attributed to passive targeting of the nanosized niosomes and confirmed by radiokinetic evaluation.

Synergistic Power of Piceatannol and/or Vitamin D in Bleomycin-Induced Pulmonary Fibrosis In Vivo: A Preliminary Study.

Oxidative stress and epigenetic alterations, including the overexpression of all class I and II histone deacetylases (HDACs), particularly HDAC2 and HDAC4, have been identified as key molecular mechanisms driving pulmonary fibrosis. Treatment with piceatannol (PIC) or vitamin D (Vit D) has previously exhibited mitigating impacts in pulmonary fibrosis models. The present study investigated the effects of PIC, Vit D, or a combination (PIC-Vit D) on the expression of HDAC2, HDAC4, and transforming growth factor-beta (TGF-ß) in the lungs; the phosphatidylinositide-3-kinase (PI3K)/AKT signaling pathway; and the antioxidant status of the lungs. The objective was to determine if the treatments had protective mechanisms against pulmonary fibrosis caused by bleomycin (BLM) in rats. Adult male albino rats were given a single intratracheal dosage of BLM (10 mg/kg) to induce pulmonary fibrosis. PIC (15 mg/kg/day, oral (p.o.)), Vit D (0.5 µg/kg/day, intraperitoneal (i.p.)), or PIC-Vit D (15 mg/kg/day, p.o. plus 0.5 µg/kg/day, i.p.) were given the day following BLM instillation and maintained for 14 days. The results showed that PIC, Vit D, and PIC-Vit D significantly improved the histopathological sections; downregulated the expression of HDAC2, HDAC4, and TGF-ß in the lungs; inhibited the PI3K/AKT signaling pathway; decreased extracellular matrix (ECM) deposition including collagen type I and alpha smooth muscle actin (α-SMA); and increased the antioxidant capacity of the lungs by increasing the levels of glutathione (GSH) that had been reduced and decreasing the levels of malondialdehyde (MDA) compared with the BLM group at a p-value less than 0.05. The concomitant administration of PIC and Vit D had a synergistic impact that was greater than the impact of monotherapy with either PIC or Vit D. PIC, Vit D, and PIC-Vit D exhibited a notable protective effect through their antioxidant effects, modulation of the expression of HDAC2, HDAC4, and TGF-ß in the lungs, and suppression of the PI3K/AKT signaling pathway.

Melodic maestros: Unraveling the role of miRNAs in the diagnosis, progression, and drug resistance of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a highly lethal form of pleural cancer characterized by a scarcity of effective therapeutic interventions, resulting in unfavorable prognoses for afflicted individuals. Besides, many patients experience substantial consequences from being diagnosed in advanced stages. The available diagnostic, prognostic, and therapeutic options for MPM are restricted in scope. MicroRNAs (miRNAs) are a subset of small, noncoding RNA molecules that exert significant regulatory influence over several cellular processes within cell biology. A wide range of miRNAs have atypical expression patterns in cancer, serving specific functions as either tumor suppressors or oncomiRs. This review aims to collate, epitomize, and analyze the latest scholarly investigations on miRNAs that are believed to be implicated in the dysregulation leading to MPM. miRNAs are also discussed concerning their potential clinical usefulness as diagnostic and prognostic biomarkers for MPM. The future holds promising prospects for enhancing diagnostic, prognostic, and therapeutic modalities for MPM, with miRNAs emerging as a potential trigger for such advancements.

miRNAs orchestration of adrenocortical carcinoma - Particular emphasis on diagnosis, progression and drug resistance.

Adrenocortical carcinoma (ACC) is an uncommon aggressive endocrine malignancy that is nonetheless associated with significant mortality and morbidity rates because of endocrine and oncological consequences. Recent genome-wide investigations of ACC have advanced our understanding of the disease, but substantial obstacles remain to overcome regarding diagnosis and prognosis. MicroRNAs (miRNAs, miRs) play a crucial role in the development and metastasis of a wide range of carcinomas by regulating the expression of their target genes through various mechanisms causing translational repression or messenger RNA (mRNA) degradation. Along with miRNAs in the adrenocortical cancerous tissue, circulating miRNAs are considered barely invasive diagnostic or prognostic biomarkers of ACC. miRNAs may serve as treatment targets that expand the rather-limited therapeutic repertoire in the field of ACC. Patients with advanced ACC still have a poor prognosis when using the available treatments, despite a substantial improvement in understanding of the illness over the previous few decades. Accordingly, in this review, we provide a crucial overview of the recent studies in ACC-associated miRNAs regarding their diagnostic, prognostic, and potential therapeutic relevance.

Decoding the role of miRNAs in multiple myeloma pathogenesis: A focus on signaling pathways.

Multiple myeloma (MM) is a cancer of plasma cells that has been extensively studied in recent years, with researchers increasingly focusing on the role of microRNAs (miRNAs) in regulating gene expression in MM. Several non-coding RNAs have been demonstrated to regulate MM pathogenesis signaling pathways. These pathways might regulate MM development, apoptosis, progression, and therapeutic outcomes. They are Wnt/ß-catenin, PI3K/Akt/mTOR, P53 and KRAS. This review highlights the impending role of miRNAs in MM signaling and their relationship with MM therapeutic interventions.

Design and Optimization of Omeprazole-Curcumin-Loaded Hydrogel Beads Coated with Chitosan for Treating Peptic Ulcers.

This study aimed to formulate a pharmaceutical dosage form containing omeprazole (OMP) and curcumin (CURC) to treat experimental peptic ulcers. OMP and CURC were preliminarily complexed with hydroxypropyl-ß-cyclodextrin for enhancing their solubilization. After that, the combined complex (CURC/OMP) was loaded to alginate beads to sustain their release and then coated with chitosan. Finally, we tested the anti-ulcerogenic impact of the best formula versus free OMP or OMP-only-loaded beads. The formulated spherical beads' diameter ranged from a minimum value of 1.5 ± 0.08 mm to 2.6 ± 0.24 mm; the swelling results ranged from 400.00 ± 8.5% to 800.00 ± 6.2%. The entrapment efficiency was in a range from 60.85 ± 1.01% to 87.44 ± 1.88%. The optimized formula (F8) showed a maximum EE% (87.44 ± 1.88%), swelling (800.00 ± 6.2%), and diameter in the range of 2.60 ± 0.24, with a desirability of 0.941. In the first hour following the administration of the free drug complex, 95% of OMP and 98% of CURC were released. This is unacceptable for medications that require a delayed release in the stomach. The initial drug release from hydrogel beads was 23.19% for CURC and 17.19% for OMP after 2 h and 73.09% for CURC and 58.26% for OMP after 12 h; however, after 24 h, 87.81% of CURC and 81.67% of OMP had been released. The OMP/CURC beads showed a more stable particle size (0.52 ± 0.01 mm) after 6 weeks. In conclusion, the OMP/CURC hydrogel beads give stronger anti-ulcer effectiveness compared to free OMP, CURC-only beads, and OMP-only-loaded beads, indicating a prospective application for managing peptic ulcers.

Cardioprotective Effect of Flibanserin against Isoproterenol-Induced Myocardial Infarction in Female Rats: Role of Cardiac 5-HT2A Receptor Gene/5-HT/Ca2+ Pathway.

Myocardial infarction (MI) is a life-threatening ischemic disease and is one of the leading causes of morbidity and mortality worldwide. Serotonin (5-HT) release during myocardial ischemia plays an important role in the progression of myocardial cellular injury. This study was conducted to investigate the possible cardioprotective effect of flibanserin (FLP) against isoproterenol (ISO)-induced MI in rats. Rats were randomly divided into five groups and were treated orally (p.o.) with FLP (15, 30, and 45 mg/kg) for 28 days. ISO was administered subcutaneously (S.C.) (85 mg/kg) on the 27th and 28th days to induce MI. ISO-induced myocardial infarcted rats exhibited a significant increase in cardiac markers, oxidative stress markers, cardiac and serum 5-HT levels, and total cardiac calcium (Ca2+) concentration. ISO-induced myocardial infarcted rats also revealed a remarkable alteration of electrocardiogram (ECG) pattern and significantly upregulated expression of the 5-Hydroxytryptamine 2A (5-HT2A) receptors gene. Moreover, ISO-induced myocardial infarcted rats showed significant histopathological findings of MI and hypertrophic signs. However, pretreatment with FLP significantly attenuated the ISO-induced MI in a dose-dependent manner, as the effect of FLP (45 mg/kg) was more pronounced than that of the other two doses, FLP (15 and 30 mg/kg). The present study provides evidence for the cardioprotective efficacy of FLP against ISO-induced MI in rats.

Development of Novel pH-Sensitive Eudragit Coated Beads Containing Curcumin-Mesalamine Combination for Colon-Specific Drug Delivery.

This research aims to develop a drug delivery system that effectively treats colitis while administering curcumin/mesalamine by coating alginate/chitosan beads with Eudragit® S-100 to target the colon. Beads were tested to determine their physicochemical characteristics. Coating with Eudragit® S-100 prevents drug release at a pH of less than 7; this was demonstrated by in-vitro release conducted in a medium with gradually varying pH to mimic circumstances in various regions of the gastrointestinal tract. This study examined the efficacy of the coated beads in treating acetic acid-induced colitis in rats. Results showed that spherical beads were formed with an average diameter of 1.6-2.8 mm, and the obtained swelling ranged from 409.80% to 890.19%. The calculated entrapment efficiency ranged from 87.49% to 97.89%. The optimized formula F13 (which was composed of mesalamine-curcumin active ingredients, Sodium alginate as a gelling agent, chitosan as a controlled release agent, CaCl2 as a crosslinking agent, and Eudragit S-100 as a pH-sensitive coating agent) demonstrated the best entrapment efficiency (97.89% ± 1.66), swelling (890.19% ± 60.1), and bead size (2.7 ± 0.62 mm). In formulation #13, which was coated with Eudragit S 100, curcumin (6.01 ± 0.04%) and mesalamine (8.64 ± 0.7%), were released after 2 h at pH 1.2; 6.36 ± 0.11% and 10.45 ± 1.52% of curcumin and mesalamine, respectively, were then released after 4 h and at pH 6.8. Meanwhile, at pH 7.4, after 24 h, approximately 85.34 ± 2.3% (curcumin) and 91.5 ± 1.2% (mesalamine) were released. Formula #13 significantly reduced the colitis, and this suggests that the developed hydrogel beads can be used for delivering curcumin-mesalamine combinations to treat ulcerative colitis after adequate research.

Canagliflozin alleviates valproic acid-induced autism in rat pups: Role of PTEN/PDK/PPAR-γ signaling pathways.

Autism is complex and multifactorial, and is one of the fastest growing neurodevelopmental disorders. Canagliflozin (Cana) is an antidiabetic drug that exhibits neuroprotective properties in various neurodegenerative syndromes. This study investigated the possible protective effect of Cana against the valproic acid (VPA)-induced model of autism. VPA was injected subcutaneously (SC) into rat pups at a dose of 300 mg/kg, twice daily on postnatal day-2 (PD-2) and PD-3, and once on PD-4 to induce an autism-like syndrome. Graded doses of Cana were administered (5 mg/kg, 7.5 mg/kg, and 10 mg/kg, P.O.) starting from the first day of VPA injections and continued for 21 days. At the end of the experiment, behavioral tests and histopathological alterations were assessed. In addition, the gene expression of peroxisome proliferator-activated receptor γ (PPAR γ), lactate dehydrogenase A (LDHA), pyruvate dehydrogenase kinase (PDK), cellular myeloctomatosis (c-Myc) with protein expression of glucose transporter-1 (GLUT-1), phosphatase and tensin homolog (PTEN), and level of acetylcholine (ACh) were determined. Treatment with Cana significantly counteracted histopathological changes in the cerebellum tissues of the brain induced by VPA. Cana (5 mg/kg, 7.5 mg/kg, and 10 mg/kg) improved sociability and social preference, enhanced stereotypic behaviors, and decreased hyperlocomotion activity, in addition to its significant effect on the canonical Wnt/ß-catenin pathway via the downregulation of gene expression of LDHA (22%, 64%, and 73% in cerebellum tissues with 51%, 60%, and 75% in cerebrum tissues), PDK (27%, 50%, and 67% in cerebellum tissues with 34%, 66%, and 77% in cerebrum tissues), c-Myc (35%, 44%, and 72% in cerebellum tissues with 19%, 58%, and 79% in cerebrum tissues), protein expression of GLUT-1 (32%, 48%, and 49% in cerebellum tissues with 30%, 50%, and 54% in cerebrum tissues), and elevating gene expression of PPAR-γ (2, 3, and 4 folds in cerebellum tissues with 1.5, 3, and 9 folds in cerebrum tissues), protein expression of PTEN (2, 5, and 6 folds in cerebellum tissues with 6, 6, and 10 folds in cerebrum tissues), and increasing the ACh levels (4, 5, and 7 folds) in brain tissues. The current study confirmed the ameliorating effect of Cana against neurochemical and behavioral alterations in the VPA-induced model of autism in rats.

Radioiodinated acemetacin loaded niosomes as a dual anticancer therapy.

A niosomal formula of acemetacin was developed to improve its tumor targeting and radio-kinetic evaluation was performed using 131I. Niosomes were prepared by ether injection method and characterized for particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE%) and in vitro drug release. Factors affecting radiolabeling with 131I were studied and optimized. Radio-kinetic evaluation was done for 131I-ACM optimum niosomal formula by intravenous (I.V) administration to solid tumor bearing mice and compared to I.V 131I-ACM solution as a control. The average droplet size, zeta potential and in vitro release after 24 h for the optimum formula were 315.23 ± 5.37 nm, -9.16 ± 2.91 and 76 %, respectively. The greatest labeling yield of 131I-ACM was 93.1 ± 1.1 %. Radio-kinetic evaluation showed a maximum tumor uptake of 5.431 %ID/g for 131I-ACM niosomal formula and 2.601 %ID/g for 131I-ACM solution at 60 min post I.V. injection. As a conclusion, niosomal formula increased tumor uptake of ACM by passive targeting of the nanosized niosomes. In addition, chemotherapeutic effect of ACM and radiotherapeutic effect of 131I were successfully combined in one treatment regimen using 131I-ACM niosomes which could be used as a hopeful dual anticancer therapy.

Formulation and Evaluation of Novel Additive-Free Spray-Dried Triamcinolone Acetonide Microspheres for Pulmonary Delivery: A Pharmacokinetic Study.

This work aimed to establish a simple method to produce additive-free triamcinolone acetonide (TAA) microspheres suitable for pulmonary delivery, and therefore more simple manufacturing steps will be warranted. The spray-drying process involved the optimization of the TAA feed ratio in a concentration range of 1-3% w/v from different ethanol/water compositions with/without adding ammonium bicarbonate as a blowing agent. Characterization of the formulas was performed via scanning electron microscopy, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction. Our results indicated that the size and morphology of spray-dried TAA particles were dependent on the feed and solvent concentrations in the spray-dried formulations. Furthermore, adding the blowing agent, ammonium bicarbonate, did not produce a significant enhancement in particle characteristics. We prepared additive-free TAA microspheres and found that TAA formulation #1 had optimal physical properties in terms of diameter (2.24 ± 0.27 µm), bulk density (0.95 ± 0.05), tapped density (1.18 ± 0.07), and flowability for deposition during the pulmonary tract, from a centric airway to the alveoli as indicated by Carr's index = 19 ± 0.01. Hence, formulation #1 was selected to be tested for pharmacokinetic characters. Rats received pulmonary doses of TAA formula #1 and then the TTA concentration in plasma, fluid broncho-alveolar lavage, and lung tissues was determined by HPLC. The TAA concentration at 15 min was 0.55 ± 0.02 µg/mL in plasma, 16.74 ± 2 µg/mL in bronchoalveolar lavage, and 8.96 ± 0.65 µg/mL in lung homogenates, while at the 24 h time point, the TAA concentration was 0.03 ± 0.02 µg/mL in plasma, 1.48 ± 0.27 µg/mL in bronchoalveolar lavage, and 3.79 ± 0.33 µg/mL in lung homogenates. We found that TAA remained in curative concentrations in the rat lung tissues for at least 24 h after pulmonary administration. Therefore, we can conclude that additive-free spray-dried TAA microspheres were promising for treating lung diseases. The current novel preparation technology has applications in the design of preparations for TAA or other therapeutic agents designed for pulmonary delivery.

Protective Effect of Pycnogenol against Methotrexate-Induced Hepatic, Renal, and Cardiac Toxicity: An In Vivo Study.

Methotrexate (MTX) is one of the most commonly used chemotherapies for various types of cancer, including leukemia, breast cancer, hepatocarcinoma, and gastric cancers. However, the efficacy of MTX is frequently limited by serious side effects. Several studies have reported that the cytotoxic effect of MTX is not limited to cancer cells but can also affect normal tissues, leading to prospective damage to many organs. In the present study, we extensively investigated the molecular and microscopic basis of MTX-induced toxicity in different organs (liver, kidney, and heart) and explored the possible protective effect of pycnogenol, a polyphenolic component extracted from the bark of P. pinaster, to attenuate these effects. Biochemical analysis revealed that administration of MTX significantly reduced the function of the liver, kidney, and heart. Histological and immunohistochemical analysis indicated that MTX treatment caused damage to tissues of different organs. Interestingly, administration of pycnogenol (10, 20, and 30 mg/kg) significantly attenuated the deterioration effects of MTX on different organs in a dose-dependent manner, as demonstrated by biochemical and histological analysis. Our results reveal that pycnogenol successfully ameliorated oxidative damage and reduced toxicity, inflammatory response, and histological markers induced by methotrexate treatment. Taken together, this study provides solid evidence for the pharmacological application of pycnogenol to attenuate damage to different organs induced by MTX treatment.

Pyrvinium pamoate ameliorates cyclosporin A- induced hepatotoxicity via the modulation of Wnt/ß-catenin signaling and upregulation of PPAR-γ.

BACKGROUND: Cyclosporin A (CsA) is an immunosuppressive agent that can be used to treat autoimmune diseases. Despite its hepatotoxicity, CsA is a backbone in organ transplantation. Pyrvinium pamoate (PP) is an inhibitor of Wnt signaling approved by the U.S. Food and Drug Administration for its anthelmintic properties. AIM: The goal of this investigation was to determine whether PP could protect against CsA-induced hepatotoxicity. METHOD: Five groups of 50 albino male mice were selected and divided into five groups; group 1 was the control, groups 2 to 4 were subjected to daily CsA (25 mg/kg, i.p), in which groups 3 and 4 were treated with graded dose of PP (0.25, 0.5 mg/kg), and group 5 was treated with PP (0.5 mg/ kg) for 21 days. The mice were sacrificed under anesthesia, and their livers were removed for histological and biochemical assessment. RESULTS: CsA was found to cause a striking increase in liver enzymes, total bilirubin, and malondialdehyde levels while significantly decreasing the levels of albumin, glutathione, and antioxidant enzymes in the treated groups. The tissue levels of tumor necrosis factor-α, interleukin-1ß, and NFКB were also significantly higher with CsA treatment. Moreover, CsA triggered a notable increase in the levels of apoptotic marker P53. CsA activated the Wnt/ß-catenin pathway by increasing WNT3a expression, frizzled receptor-7, ß-catenin, and c-myc. On the other hand, the levels of PPAR-γ decreased significantly with CsA. CsA-induced alterations in the previously stated parameters were greatly reduced by PP, indicating its antioxidant, anti-inflammatory, and antiapoptotic properties. CONCLUSIONS: PP may be considered as a promising agent to prevent CsA hepatotoxicity.