Contents:
Aim
The effectiveness and safety of erythromycin for treating mycoplasma pneumonia in pediatric patients is a subject of significant interest. This study aims to conduct a systematic review and meta-analysis to assess the efficacy and safety of erythromycin in the treatment of mycoplasma pneumonia in children,with the goal of providing evidence-based recommendations for pediatric care.
Methodology
We systematically reviewed randomized controlled trials published prior to January 1, 2024, that evaluated the efficacy and safety of erythromycin in the treatment of mycoplasma pneumonia in children. Outcome measures of primary concern include clinical efficacy, complications or adverse events. We used the inverse variance method to perform a meta-analysis of random effects, representing the effects in terms of Standardized Mean Difference (SMD) or Mean Difference (MD) and giving a 95% Confidence Interval (CIs). In addition, we performed a risk assessment of bias using the Cochrane tool. A total of 68 relevant studies were searched and 4 literatures meeting the requirements were included, with a total of 599 children.
Results
The results of meta-analysis showed that the efficacy of erythromycin in the treatment of mycoplasma pneumonia in children was not statistically significant compared with conventional treatment [RR=12.31, 95%CI (-1.23, 25.86)]. The safety of erythromycin in the treatment of mycoplasma pneumonia in children was significantly different from that of conventional treatment [RR=5.55, 95%CI (2.65, 11.65)]. Subgroup analysis showed that the meta-analysis results of the three literatures showed RR=1.95, 95%CI (1.01,3.74), suggesting that there was no statistically significant difference between the two groups of children with diarrhea. The results of meta-analysis of the two literatures showed that RR=1.95, 95%CI (0.63, 6.04), indicating that there was no statistical significance in the difference between the two groups of children with abdomina. The results of meta-analysis of the two literatures showed that RR=3.95, 95%CI (1.62, 5.58), indicating that there was a statistically significant difference between the two groups of pain children. The results of trial sequence analysis showed that the results of clinical efficacy and safety were considered reliable and stable and the safety of the experimental group was better than that of the control group in the treatment of pediatric mycoplasma pneumonia.
Conclusion
Erythromycin is effective and safe in the treatment of mycoplasma pneumonia in children. Due to individual differences and the severity of the disease, there are certain differences in clinical treatment effects and some adverse reactions and drug resistance problems also need to be paid attention to and solved.
The process of officially calling something back to its original or initial location is termed as “recall.” Pharmaceutical recalls involve requesting to get back a product after it leaves the manufacturer to reach the distributor, retailer, or consumer. In place of the discovery of defect that affects the quality safety and efficacy of the product. Drug product recalls occur due to various reasons such as wrong or unapproved drugs, undeclared ingredients, contamination, incorrect information, and particulate issues. The probable risks or issues that arise due to a product recall or claims related to product liability and legal issues. A product recall should be perceived as an opportunity for the elimination of personal injury to the patient and damage to the reputation of the company products and rebuilding trust. Quality culture across the organization is a means of product recall prevention. In this comprehensive analysis, we delve into the drug recall statistics spanning the fiscal year 2018 to 2023 (up to July), focusing on the distinct challenges posed by recalls attributed to a lack of sterility assurance and those due to impurity profiles. Unveiling critical insights, the study highlights the impact of these issues on the pharmaceutical industry’s commitment to ensuring the safety and quality of drug products. This unique analysis presents a call to action for collaborative efforts between regulatory authorities, manufacturers, and healthcare professionals. Emphasizing the value of transparent communication and proactive measures, we explore avenues to mitigate recalls and reinforce public trust in pharmaceutical products. By drawing insights from past incidents, the industry can forge a path towards a safer, more reliable future, where drug recalls due to sterility and impurity issues become rare occurrences. Swift and thorough recalls are vital to ensure patient safety. The rising trend in recalls, caused by company discovery, customer complaints, or FDA observations, impacts sales, customer relations, and supply chains. Recalls involve planned actions, including depth of recall, public alerts, and effectiveness checks.
Plant secondary metabolites play a vital role in developing numerous industrial products. Nutritive products developed from natural sources have better acceptance and demand than chemically synthesized products. Biologically active secondary metabolites play an important role in synthesizing various pharmaceutical drugs, and demand for its industrial manufacture is on the rise. In vitro cell suspension cultures using elicitors are a means of increasing the production of secondary metabolites in plant cells. Plant cells subjected to stress can be regulated to produce secondary metabolites using biotic and abiotic elicitors leading to either increase in cell volume or an increase in the rate of cell division, or both. The review aims to present the primary role of bioactive compounds and the potential of regulated in vitro cell suspension cultures in elevating the yield of pharmacologically crucial plant secondary metabolites via the active participation of various elicitors.
Aim
Special packaging known as “child-resistant packaging” is intended to minimize the possibility of kids eating harmful substances. The Poison Prevention Packaging Act of 1970 confers jurisdiction to regulate this on the U.S. Consumer Product Safety Commission and amended in 1995 to include senior-friendly packaging which became effective in 1972.
Materials and Methods
For the protection of children, regulations apply to prescription pharmaceuticals, over-the-counter medicines, insecticides, home chemicals, and unit packaging, such as blister packets. The elderly and those with disabilities have a challenge with child-resistant packaging. Regulations require package and performance tests to be child-resistant and senior-friendly. Certain standards for special packaging like ISO 8317 Requirements and testing procedures for re-closable packages, EN 862 (2005), EN 14375 (2003), ISO 13127 Mechanical test methods for re-closable child-resistant packaging, ASTM D3475 Standard Classification for Child-Resistant Packages (CRPs). Use of CRP Indices such as Package Type (e.g., Aerosol over cap), ASTM Type (e.g., re-closable packaging-continuous thread closure). CRP Manufacturer, CRP Name, Regulations in countries (Canada, The Netherlands, United States, United Kingdom). A few myths concerning packaging for children.
Results and Conclusion
Reckitt Benckiser is requesting the FDA to require not only child-resistant, unit-dosed containers but also to provide educational programs aimed at lowering the likelihood that children would be exposed to the opioid dependency treatment medicine buprenorphine.
Aim/Background
This review aims to enhance understanding of Mycoplasma pneumoniae (MP) infection and Macrolide-Resistant Mycoplasma pneumoniae (MRMP) pneumonia, emphasizing their epidemiological characteristics and resistance mechanisms. MP is a major cause of Community-Acquired Pneumonia (CAP) in children, with potential extra-pulmonary manifestations. The objective is to guide early diagnosis and timely treatment, addressing the challenges posed by MP’s resistance to β-Lactam and vancomycin drugs.
Materials and Methods
The review examines the current status of macrolide antibiotics, such as erythromycin, azithromycin, clarithromycin, josamycin, and roxithromycin, highlighting their mechanisms of action and interference with microbial protein synthesis. It also explores laboratory testing methods for identifying MRMP and assessing resistance mechanisms.
Results
The review synthesizes knowledge on MRMP infection characteristics and epidemiology, highlighting the global increase in MRMP cases, which limits treatment options for pediatric patients. It discusses resistance mechanisms and the urgent need for effective clinical treatments due to rising macrolide resistance.
Conclusion
This review underscores the critical need for a deeper understanding of MP infection and the alarming rise of macrolide resistance. It emphasizes judicious use of macrolide antibiotics and advocates for ongoing research to develop alternative treatment strategies. The findings highlight the necessity for enhanced surveillance, accurate laboratory testing methods, and updated clinical guidelines to manage MRMP pneumonia effectively, particularly in the pediatric population.
Background
The desire for novel drugs and bioactive ingredients to combat serious illnesses like cancer has grown dramatically. A great deal of research is being done to discover and create new medications.
Aim
According to research, cirrhosis brought on by the Hepatitis C and B Viruses (HCV) is thought to be responsible for almost half of occurrences of Hepatocellular Carcinoma (HCC). These viruses alter the DNA of the liver cells they infect, turning healthy liver cells into cancerous ones. HCC is a clinical condition where the cancer typically commences in the liver. Human liver cancer HepG2 cells are treated with Rutaecarpine (RUT), a versatile medicinal plant derived from Evodia rutaecarpa.
Materials and Methods
RUT was administered to HepG2 cell lines at different concentrations and the IC50 value was found. The cell line treated with RUT was then stained with the dual dye AO/EtBr to confirm apoptosis. In a similar manner, HepG2 control and RUT-treated cell lines underwent 24 hr of mitochondrial labeling and estimated to have loss in mitochondrial membrane potential which releases proteins that significantly contribute to apoptosis.
Results
Rutaecarpine significantly reduces cell viability by 50% inhibiting cell growth, losing mitochondrial membrane potential and Increased expression of apoptotic indicators, such as caspase-3, caspase-8 and caspase-9, were evaluated in RUT treated liver cancer cells using ELISA.
Conclusion
According to the study’s findings, in HepG2, RUT induces apoptosis and via a mechanism mediated by the mitochondrial membrane.
Objectives
To explore the curative effect of QihaPingchuan Capsule combined with triple therapy [Inhaled Corticosteroid (ICS)+Long-Acting β2 receptor Agonist (LABA)+Long-Acting Anticholinergic drug (LAMA)] on Chronic Obstructive Pulmonary Disease (COPD).
Materials and Methods
A total of 92 patients with COPD admitted to the hospital were enrolled between January 2021 and October 2022. According to the random number table method, they were divided into Group A and Group B, with 46 cases in each group. Group B was given routine symptomatic treatment and triple therapy, while Group A was additionally treated with Qiha Pingchuan Capsules. All were treated for two weeks. The clinical curative effect, scores of TCM syndromes and COPD Assessment Test (CAT), 6-Minute Walk Distance (6MWD), Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1), Peak Expiratory Flow (PEF), Partial Pressure of Oxygen (PO2), partial Pressure of Carbon dioxide (PCO2), serum C-Reactive Protein (CRP), Interleukin-8 (IL-8) and incidence of adverse reactions were compared between the two groups before and after treatment.
Results
The total response rate of treatment in group A was significantly higher than in group B (89.13% vs. 71.74%, p <0.05). After treatment, TCM syndromes and CAT scores in group A were significantly lower than those in group B and 6MWD was significantly longer than in group B (p <0.05). FCV, FEV1 and PEF in group A were significantly higher than in group B (p <0.05). PO2 in group A was significantly higher than in group B, while PCO2, CRP and IL-8 levels were significantly lower than those in group B (p <0.05). There was no significant difference in the incidence of adverse reactions between group A and group B (15.22% vs. 10.87%, p >0.05).
Conclusion
QihaPingchuan Capsule combined with triple therapy (ICS+LABA+LAMA) can improve the clinical curative effect, effectively relieve clinical symptoms and improve pulmonary function and inflammatory response in COPD patients, with reasonable safety.
This study meticulously delineates the research progression, focal points, developmental path and emergent evolutionary trajectories of computational intelligence within the domain of ethics. A comprehensive quantitative report, embodying bibliometric principles, was prepared using the Web of Science Core Collection database. The methodology involved conducting an extensive search for original articles and reviews related to “ethical artificial intelligence” Relevant data from these sources were extracted and integrated into CiteSpace and Vosviewer for bibliometric and knowledge mapping analysis. The R package was used as an auxiliary tool in this process, facilitating the creation of co-occurrence networks and providing necessary information on authors, countries/regions, institutions, documents, references and keywords. This investigation includes an aggregate of 327 articles. The research on ethical AI originated in 2001 and experienced a marked escalation from 2015 onwards. Luciano Floridi has made the most significant contribution with regard to the volume of scholarly outputs. The USA emerged as the region with the most prolific output and the University of Oxford stands as the institution contributing the greatest amount of articles. The periodical registering the most prolific scholarly contributions is “Science and Engineering Ethics”. Keyword analysis reveals that, in addition to topic-specific keywords such as “artificial intelligence”, “big data” and “artificial neural network”, there are also keywords that align with ethical theory research, such as “ethic issue” and “medical ethics”, as well as those congruent with technical application research, including “technology”, “model” and “design”. These keywords substantially shape the principal directions of future research in this domain. The study of ethics in the field of AI is undergoing significant growth and holds immense potential. It is imperative to foster international and interdisciplinary collaboration among nations and institutions in order to advance further. As AI theories and technologies continue to mature, research addressing the ethical dimensions of AI, its technical applications, or the integration of both, will undoubtedly become key areas of sustained development and innovation in the future.
Background
Cholesterol synthesized in astrocytes of the cerebrum plays a pivotal role in regulating hippocampal neurogenesis and cognitive function. Dysregulation of cholesterol metabolism has emerged as a key contributor to the pathogenesis of Parkinson’s disease. Elevated cholesterol levels in the brain are associated with increased oxidative stress and subsequent neurodegeneration of hippocampal pyramidal neurons, culminating in cognitive impairment. Berberine, an isoquinoline alkaloid has the potential to modulate cholesterol synthesis through HMG-CoA inhibition.
Aim
This study aims to elucidate the therapeutic potential of berberine in mitigating cognitive impairment in Parkinson’s disease by conferring protection to hippocampal pyramidal neurons through regulating cholesterol homeostasis.
Materials and Methods
Parkinson’s disease was induced in male Sprague Dawley rats through the administration of rotenone (intraperitoneal, 2.5 mg/kg) for 42 days, followed by treatment with the berberine (oral administration, 10 mg/kg and 40 mg/kg) for 21 days. The efficacy of berberine was assessed through evaluations encompassing cognitive function, motor coordination, locomotor activity, biochemical analyses, and histopathological examinations.
Results
Our findings revealed that berberine, administered intraperitoneally at a dose of 40 mg/kg, effectively ameliorated the symptoms associated with Parkinson’s disease. This amelioration was concomitant with reduced cholesterol levels within the brain and an elevation in dopamine levels when compared to the disease-induced control group. The hippocampus of the berberine-treated group showed preserved pyramidal neurons and a decrease in macrophage and microglial infiltration, which were strongly correlated with the reported improvement in cognitive performance.
Conclusion
Our study underscores the potential therapeutic utility of berberine in mitigating cognitive impairment in Parkinson’s disease. The findings presented here provide valuable insight into the mechanisms underlying the beneficial effects of berberine in Parkinson’s disease and suggest its promise as a therapeutic agent in managing cognitive deficits associated with this neurodegenerative disorder through regulating cholesterol homeostasis.
Background
Klebsiella pneumoniae, a Gram-negative bacterium, is an established nosocomial pathogen that is particularly dangerous to immunosuppressed individuals, causing diseases such as sepsis, pneumonia, urinary tract infections and respiratory tract infections. The emergence of multidrug resistant strains of this bacterium poses a significant challenge to current therapeutic strategies, highlighting the urgent need for new drug targets.
Materials and Methods
Our study highlights the shikimate pathway as a source of such targets, given its role in the production of essential aromatic compounds in various organisms, but its absence in humans. We focus on Shikimate Kinase 1 (SK-1), encoded by the aroK gene in K. pneumoniae and use it as a model for inhibitor development. Through comparative modelling, structural validation is using Ramachandran plots, ERRAT and Verify3D and stability checks using energy minimization and molecular dynamics simulations.
Results
In the Ramachandran plot validation, AlphaFold2 performed better than the other three predicted models (SWISS-MODEL, Phyre2 servers, I-TASSER). The Ramachandran plot analysis showed 90.8% residues in the preferred region, 8.8% residues in the allowed region. When Desmond’s energy minimization calculations were applied to the models, AlphaFold2 showed the lowest energy. In addition, MD simulations representing a stable conformation were applied to the reduced structure.
Conclusion
This provides a basis for molecular coupling and the exploration of new inhibitors, offering promising avenues for the development of treatments against K. pneumoniae.
Background
CDK4 play a pivotal role in cell cycle regulation, making it a critical players in the development and progression of cancer. In recent years, there has been a growing interest in targeting CDK4 for cancer therapeutics, with a focus on the identification and development of small molecule inhibitors.
Materials and Methods
This work, using a strong in silico and in vitro methodology, reveals Betulinic Acid’s inhibitory efficacy against CDK4 for cancer therapy. Betulinic Acid, a pentacyclic triterpenoid with a variety of characteristics, has emerged as a promising CDK4 inhibitor.
Results
The study identifies key CDK4 binding sites using high-resolution structural modeling and cavity detection. Betulinic Acid’s highest fitness and predicted binding affinity were found, supporting its drug-likeness properties. Its pharmacokinetic viability, biological properties, and cytotoxicity assays show its concentration-dependent effects on cancer cells (A549 and NCI-H460). Molecular-level validations reveal a significant decrease in CDK4 mRNA expression and kinase activity, reinforcing its potential as a CDK4 inhibitor.
Conclusion
In conclusion, this comprehensive study bridges structural insights with experimental validations, positioning Betulinic Acid as a promising therapeutic agent for CDK4 inhibition in cancer, particularly lung cancer. The findings contribute significantly to drug discovery, paving the way for further preclinical and clinical investigations in the quest for effective cancer treatments.
Background
To develop a new drug approach, it is necessary to understand possible ways by which suppression of depressive symptoms can be achieved at the biochemical level. One such protein, which can help relieve depression when targeted, is AMP-Activated Protein Kinase (AMPK). The present in vivo study has focussed on AMPK and inflammatory cytokines as potential targets for improving Brain-Derived Neurotrophic Factor levels (BDNF) in depression.
Materials and Methods
A parallel therapy was administered for standard (Fluoxetine (10 mg/kg), monotherapy (Metformin (200 mg/kg) and Quercetin (20 mg/kg) and combination of half dose (Metformin (100 mg/kg)+Quercetin (10 mg/kg) and full dose (Metformin (200 mg/kg)+Quercetin (20 mg/ kg) for 3 weeks in mice. The study comprises behavorial parameters assessed using locomotor activity, Forced Swimming Test (FST), elevated plus maze, Tail Suspension Test (TST) and Sucrose Preference Test (SPT).
Results and Conclusion
The results obtained depicted that the high-dose combination doses decreased immobility time, anhedonia and increased open-arm exploration in behavorial tests. Significant difference observed in Metformin (200 mg/kg)+Quercetin (20 mg/ kg) treated group at *p <0.1 [locomotor activity, FST, EPM (dark and open arm) and SPT], ***p <0.01 (TST). Moreover, the combination lowered the number of neurodegenerative cytokines such as Tumour necrosis factor-α, Interlukin-1β, Interlukin-6 (**p <0.05), but Brain Derived Neurotropic Factor (* p <0.1) and corticosterone levels (** p <0.05) were raised indicating antidepressant effects. The studies suggested that metformin and quercetin in combination act as an antidepressant.
Background
Diabetic Nephropathy (DN) is one of the serious complications associated with a prolonged diabetic condition. DN continues to be the primary cause of morbidity and mortality among diabetic patients globally.
Objectives
The objective of the current work is to study the nephroprotective properties of leonurine in the diabetic nephropathy model.
Materials and Methods
The experimental rats were induced with DN through an administration of 65 mg/kg of Streptozotocin (STZ) and the DN rats were treated with leonurine for 12 weeks. Following the treatment period, the blood glucose, insulin and glycosylated Hemoglobin (HbA1c) levels were evaluated. The renal function markers, including creatinine, kidney injury molecule, ROS level, lipid profiles and pro-inflammatory cytokine levels, were examined using the kits. The renal tissues of the experimental rats were subjected to the histological studies.
Results
The outcomes of the present work found that the leonurine treatment considerably increased the insulin levels, decreased blood glucose and HbA1c levels and decreased ROS production in the DN rats. In the DN rats, the treatment of leonurine significantly reduced the inflammatory markers, renal fibrotic markers, kidney dysfunction markers and lipid markers. The histological analysis results also confirmed leonurine's therapeutic effects against DN in rats.
Conclusion
The current findings suggest that leonurine has the capacity to be a talented candidate to treat DN.
Background
Atherosclerosis is a complex progressive pathological process that produces lesions in the inner wall of an artery because of the abnormal lipid metabolism, and dysregulation of inflammatory processes. Increased levels of Low-Density Lipoprotein (LDL) and Total Cholesterol (TC) lead to hyperlipidaemia which is a major risk factor for atherosclerosis.
Materials and Methods
This research comprises the assessment of hydro-alcoholic extract of the aerial part of Euphorbia lactea on high-fat diet-induced atherosclerosis in rats. The hydroalcoholic extract with doses (200 and 400 mg/kg body mass, p.o.) was assessed for hypolipidaemic activity. The blood samples were collected in heparinized tubes at the end of the experiment, and then centrifuged and collected the supernatant to determine Triglyceride (TG), High-Density Lipoprotein (HDL), LDL, TC, and Very Low-Density Lipoprotein (VLDL). The atherosclerotic markers including Creatine Phosphokinase (CPK), Alanine Transaminase (ALT), Alkaline Phosphatase (ALP), Lactate Dehydrogenase (LDH), and Aspartate Transaminase (AST) section of heart aorta were examined by histopathology.
Results
The results exhibited significantly reduced TG, LDL, TC, and VLDL levels. However, the HDL level was significantly increased as compared with induced rats. This current research demonstrated the anti-atherogenic potential of hydroalcoholic extract of the aerial part of E. lactea.
Conclusion
Overall, the results revealed that plant extract at different doses lowered LDL and TC levels significantly. Hence it could be used to benefit from atherosclerosis and its associated risk factors inclusive of heart attack, and stroke. Furthermore, it might be used as a traditional medicine against CVD and beneficial in the treatment of hyperlipidemia-induced atherosclerosis and diabetes mellitus.
Background
The extract of Terminalia chebula was explored with a new perspective to control tomato bacterial wilt, opening up a new way in agriculture to control plant disease in an organic way with less impact on the environment, ecosystem and consumers.
Materials and Methods
The preliminary study reveals the presence of phenolic compounds, coumarins and anthroquinones in the ethanol extract and was analysed further by GCMS and NMR to identify the compounds, structure and functional group in the EE. The macro-dilution superior to diffusion method to find the rate of inhibition to measure the potential of phytochemicals in Ethanol Extract (EE)
Results
The optimum of 0.1 mg/mL of crude EE inhibits 56% of Ralstonia solanacearum (RS) effectively up to 96% with 0.8 mg/mL. The extent of the in vitro, in vivo experiment on tomato (Lycopersicum esculentum) to check any toxic compounds in EE that hinder plant growth and the absence of such compounds makes the EE a good source of organic alternatives for synthetic compounds. Simultaneously to find biologically active compounds reduces the disease severity in the inoculated plant. The pot culture experiments were conducted with seeds and plants of Lycopersicum esculentum that received EE against induced RS infection.
Conclusion
The five phytochemicals in crude ethanol extract have bioactivity on host plants inoculated with Ralstonia solanacearum, the severity of the disease decreased with that of the diseased plant not receiving any treatment. The extract-treated plant was measured in height and weight to non-treated control plants and there was a significant difference between groups. Identified compound affinity was measured with molecular docking and interpreted.
Introduction
The domestication of Satureja calamintha, either because of its superior tolerance to disease and environmental factors or because of its potential for larger quantities of useful chemicals.
Materials and Methods
wild plants were harvested in the Ksar El Kabîr region, Morocco, and seeds were planted in open-air plots. Part of the cultivated plant was then harvested after one year of planting, while the other was harvested after two years.
Results
The results show that the plant cultivated and harvested in the second year is characterized by a slightly higher polyphenol content for all three extraction methods than the same plant cultivated in the first year, and that the spontaneous plant, particularly the decoction, has the highest content (174.42±0.52 mg GAE/g extract), while the infused extract has the lowest content (123.242±5.64 mg GAE/g extract). Decoction and infusion remain suitable extraction extraction methods for total flavonoids for the plant grown in the second year, representing (86.23±0.12 mg EQ/g extract) and (76.45±0.06 mg EQ/g extract) respectively, followed by macerate of the spontaneous plant (57.7±1.46 mg EQ/g extract). In terms of antioxidant activity, the extract obtained by decoction and harvested in the second year showed high antioxidant activity against DPPH (IC50=1.174±0.141mg/mL), FRAP(EC50=4.254±0.03) and ABTS (IC50=9.969±0.09 mg/mL), while maceration showed low activity against the same three tests.
Conclusion
The aqueous extracts of the studied spontaneous and cultivated plants showed positive results for all activities and were characterized by an increase in phytochemicals, particularly in the extracts from the second year.
Background
Prostate cancer is the leading cause of death in men over the age of 50, making it one of the most common cancers. Current treatments available such as chemotherapy, surgery are associated with many side-effects. Due to non-specificity and poor solubility of many anticancer drugs, less amount of drug is available at the absorption site. The current study aimed to develop Nanostructured Lipid Carriers (NLCs) of the poorly soluble anticancer drug Flutamide.
Materials and Methods
Flutamide-loaded Nanostructured Lipid Carriers (NLCs) containing biocompatible lipids Precirol ATO 5 (Solid lipid), flaxseed oil (Liquid lipid) and surfactants were synthesized using the melt emulsification ultrasonication method. Koliphor RH40 and Tween 80 were used in combination in 1:1 ratio.
Results
The interaction of drug and excipients was investigated using Fourier Transform Infrared (FTIR). Phase transition of Flutamide was confirmed using differential scanning calorimetry during the processing of NLCs. Solubility Flutamide increased significantly when it was prepared in the form of NLCs. Flutamide-loaded NLCs were found to be eighteen times more soluble in distilled water than the pure drug. Flutamide loaded NLCs were five times, three times, and four times more soluble in pH 1.2, 6.8, and 7.4 PBS than the pure drug.
Conclusion
According to the findings, Flutamide can be formulated into nanostructured lipid carriers with improved solubility.
Background:
Boswellic acids are naturally occurring pentacyclic terpenoids that have revealed valuable anti-inflammatory, antiproliferation and anticancerous activities. Instead of these effects boswellic acids also possess antibacterial potential reported in the literature. However, these phytoconstituents associated with low aqueous solubility and bioavailability restrictions. The present study aimed to explore the antibacterial effects of boswellic acids by means of nano formulations.
Materials and Methods:
Chitosan was utilized as a natural biocompatible material for nanoparticles preparation, employing the ionic gelation technique as an effective approach. Well diffusion method was used to test antibacterial activity against four pathogenic bacteria (Gram-positive bacteria: Staphylococcus aureus, Bacillus subtilis; Gram-negative Salmonella typhi, and. Escherichia coli. Micro broth dilution technique was used to determine the minimum inhibitory concentration.
Results:
Boswellic acids-loaded nanoparticles displayed spherical particles with particle size 104.6 nm and 0.081 PDI value, respectively with smooth-surfaced spherical particles. Boswellic acids chitosan nanoparticles have a greater zone of inhibition against Salmonella typhi than Boswellia serrata extract with MIC values of 3.91 and 7.81 μg/ mL, respectively.
Conclusion:
Poorly soluble boswellic acids were successfully encapsulated in chitosan nanoparticles and exhibited improved antibacterial activity compared to Boswellia serrata extract.
Background:
The goal of the current research was to use the straight forward, scalable, and economical Liquisolid compact to improve the dissolution profile of the poorly soluble medication Ramipril.
Objectives:
Utilising various polymers and liquid vehicles, the study's objective was to develop and characterise Liquisolid compact.
Materials and Methods:
Ramipril liquisolid were formulated using Propylene glycol and PEG 400 as liquid vehicle, MCC as a carrier, Aerosil 200 as a coating material. By using differential scanning calorimetry, the crystallinity of the newly developed drug formulation and the interactions between excipients were investigated. No interaction between the medication and excipients was established by FTIR tests.
Results:
The friability, hardness, weight variation, disintegration test, and in vitro dissolution investigations of all formed systems were evaluated for post-compression parameters. The optimized F9 formulation showed better results in vitro dissolution of 97.91% at 60 min, when compared with the marketed which showed 77.28% at 60 min.
Conclusion:
The drug release rates from liquisolid compacts were substantially higher than those from commercial formulations, which points to a potential strategy for speeding up the breakdown of medications that aren't very water-soluble.
Background:
In this study, it was aimed to prepare orally disintegrating tablet formulations of amlodipine besylate by applying the experimental design.
Materials and Methods:
A face-centered, central composite 32 full factorial design was applied to evaluate the effects of filler ratio (MAN: MCC; X1) and super disintegrant percentage (SSG; X2) on the critical tablet characteristics such as tensile strength (Y1), disintegration time (Y2) and dissolution rate (5th min) (Y3).
Results:
The Quadratic model showed good predictability (p<0.0001) on tablet tensile strength and the linear model was found to be suitable for disintegration time and dissolution time profiles (p<0.001 and p>0.05 respectively). In addition to the compendial quality control tests for tablet formulations, a texture analyzer with the tablet disintegration rig fixture was also used for the disintegration test and onset of disintegration (s), end of disintegration (s), disintegration rate (mm/s), duration of swelling (s), swelling distance (mm), residual height (mm) values were obtained.
Conclusion:
It was determined that F9, with the highest MAN: MCC (75:25) and SSG (10%) ratios, met all pharmacopeia standards and gave the best disintegration time results (18.55±1.28 s), which is a very crucial factor for orally disintegrating tablet characterization, compared to other formulations.
Background:
Polar drugs make it difficult to cross nasal cells. Trimethyl Chitosan (TMC) microspheres help absorption by opening junctions, increasing drug retention. Pregabalin absorbs well orally but delays crossing the brain, limiting emergency seizure treatment. The present study aimed to develop pregabalin-loaded TMC microspheres for intranasal administration in epilepsy.
Materials and Methods:
The microspheres were prepared by ionotropic gelation method using TMC and glutaraldehyde by varying the formulation and processing parameters and have been characterized for the physicochemical, drug release and pharmacodynamic properties.
Results:
The microspheres' particle size was 10.71- 22.85 μm with a positive zeta potential of 25.1. At 0.6% TMC, particle size was 14.05±1.24 μm, increasing to 22.85±1.48 μm at 1% TMC concentration, suitable for administration in the nasal cavity without the risk of passing to the lower respiratory tract. TP3 batch (1:1 pregabalin: TMC ratio) had 91.64% entrapment efficiency. Over 90% of drug release was achieved in in vitro and ex vivo studies using sheep nasal mucosa. The bioadhesion potential measured on sheep nasal mucosa reached 86.29±1.41%. Moreover, the excised sheep nasal mucosa exhibited no morphological toxicity, indicating a high level of biocompatibility. The microspheres significantly delayed the commencement of clonic convulsion (210 s) and presented complete protection (100%) against pentylenetetrazol-induced seizures in mice.
Conclusion:
Pregabalin-loaded TMC microspheres were a promising approach for incorporating hydrophilic drugs and have great potential for nasal administration of pregabalin.
Background:
Nanotechnology has made tremendous progress in drug development and delivery. The functionalization of nanoparticles with various biological agents facilitates the drug delivery and treatment of various cancers.
Objectives:
The current work was conducted to synthesize the chitosan-nickel oxide-amygdalin hybrid nanomaterials (Chitosan-NiO-Amygdalin HNMs) and evaluate their antimicrobial and cytotoxic effects on liver cancer (Hep3B) and breast cancer (MCF-7) cells.
Materials and Methods:
The synthesized Chitosan-NiO-Amygdalin HNMs were characterized using various methods, including UV-visible spectroscopy, PL, XRD, DLS, SEM, TEM and FT-IR analyses. The antibacterial property of Chitosan-NiO-Amygdalin HNMs was assessed by the disc diffusion method against various pathogens. The cytotoxicity of Chitosan-NiOAmygdalin HNMs on Hep3B and MCF-7 cells was assessed by an MTT assay.
Results:
The synthesis of Chitosan-NiO-Amygdalin HNMs was confirmed by a UV-vis spectrophotometry study. The PL emission spectrum of the Chitosan-NiO-Amygdalin HNMs shows their optoelectronic properties. The XRD patterns reveal that the HNMs possess a cubic crystal structure. The SEM images showed that the HNMs exhibit hexagonal structures. TEM images illustrate HNMs with hexagonal morphology. The HNMs have also shown potential antibacterial effects against various pathogens. The Chitosan-NiO-Amygdalin HNMs effectively inhibited the viability of both Hep3B and MCF-7 cells.
Conclusion:
The results of this work suggest that Chitosan-NiO-Amygdalin HNMs exhibit potential to be a prospective therapeutic agent in the future to treat cancer and other diseases.
Background:
Every year more than 1 billion prescriptions are written for all NSAIDs and yet the quest to develop new NSAIDs remains prominent.
Objectives:
The current investigation's goal was to synthesize and assess the anti-inflammatory potential of a few more recent 1,2,4-triazole derivatives.
Materials and Methods:
The synthesis of the 1,2,4-triazole compounds (SPG1-5) was accomplished in three distinct steps involving formation of hydrazide of ibuprofen and followed by cyclization to 1,2,4-triazole nucleus and ultimately formation of Schiff’s base in the final step.
Results:
Each compound was dark brown in color and were obtained in 65-71% yields and was insoluble in water and hexane whereas SPG2 and SPG3 were soluble in methanol and all compounds were soluble in chloroform. The compounds were evaluated for in vitro anti-inflammatory potential utilizing albumin denaturation and inhibition of protease action methods. With SPG4 having the best ability to produce the inhibition (62.44±2.889%) at a concentration of 500 g/mL, all the substances showed dosage-dependent inhibition of albumin denaturation. SPG4 was able to inhibit protease activity (46.63±3.211%) at 500 g/mL and the antiprotease efficacy was also dosage-dependent.
Conclusion:
It was evident that the triazole derivatives were able to display moderate anti-inflammatory action and could be optimized to develop lead molecule.
Background:
A lot of coumarin-1,2,3-triazole hybrids have been reported to show antibacterial activities, but most of them are unexplored in clinical studies. Herein, we wish to apply in silico docking, physiochemical predictions and molecular dynamics simulation studies on coumarin-1,2,3-triazole hybrids to explore their successful transformation in to broad spectrum antibacterial agent for clinical use.
Materials and Methods:
A library of 196 compounds with the coumarin-1,2,3-triazole motif showing antibacterial activity against various pathogenic bacteria was generated, and molecules were in silico screened for their binding affinities through molecular docking against six antibacterial targets Dihydropteroate synthase (PDB, ID:1TX2), Penicillin-binding protein-3 (PDB, ID:3OCN), DNA Gyrase-B24 (PDB, ID:6YD9), UDP-N- Acetylglucosamine enolpyruvyl transferase (PDB, ID:1 UAE), Sortase A (PDB, ID:2MLM), and Dethiobiotin synthetase (PDB, ID:4WOP) using AutoDock Vina. On the basis of high docking score and suitable physiochemical and ADMET parameters hybrids 134, 143, 174, and 176 were subjected to 100 ns of Molecular Dynamics (MD) on GROMACS to investigate the protein-ligand complex’s stability.
Results:
All the coumarin-1,2,3-triazole hybrids docked well with the target antibacterial protein and most of them exhibited higher binding affinity than the co-crystallized ligands of the respective proteins. MD simulation results in terms of Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), Radius of gyration (Rg) and distribution of hydrogen bonds were in complete agreement of docking scores indicating for stable ligand-target bonding.
Conclusion:
This study provides strong evidence for coumarin-1,2,3-triazole hybrids to be excellent antibacterial agents effective on both Gram-positive and Gram-negative pathogenic strains and hybrid 176 may be considered the best out of all.
Background:
Penciclovir is a medication for antiviral therapy for curing different kinds of herpes virus infections. The four contaminants are the starting materials of Penciclovir which are present at a trace level in the drug in which one of its impurities is its isomer. Purinediol Hydrochloride, N7-Isomer, Monoalkyl contaminant and Diacetyl Purine are the four potential impurities present in the drug.
Materials and Methods:
The separation was achieved in the Zorbax SB C8 column using a gradient elution of 10 mM Ammonium bicarbonate in water as a buffer and a mixture of Methanol and Acetonitrile in the ratio of 20:80 v/v at a flow rate of 0.6 mL/min at 40°C. The Agilent Q-TOF 6540 series instrument was used in positive polarity in the scan range of 50-100 m/z. The sensitive and rapid Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) technique was developed for the quantification of four impurities present in the drug.
Results:
Various validation parameters have been studied. The correlation coefficients of impurities and their linearity values are quite satisfactory within the examined range. The proposed method was sensitive in the linearity range from 0.6 ppm to 12.0 ppm.
Conclusion:
This method can be used to identify the impurities in Penciclovir drug substances during manufacturing.
Background:
The bioavailability of an element and its toxicity based on its chemical species. According to IUPAC the concept of chemical speciation is defined as it is a form of an element according to its oxidation state, isotopic composition, or complex and molecular structure. The speciation studies are profoundly plays a major role in studying the nature of trace elements in a human organism. Speciation of an element has a noticeable impact on bioavailability, distribution and toxicity. These studies have vital role in medical and pharmaceutical sciences.
Materials and Methods:
The present investigation conducted by using pH meter, processing of data done by Gran titration. To obtain best-fit chemical models, a modelling strategy such as SCPHD is used and a computer program MINIQUAD 75 is also employed for the refinement of results.
Results:
In the present investigation we considered the effect of dielectric constants of Dimethyl sulfoxide (DMSO) on stability constants of CoII, Ni” and CuII with 5-Sulfosalicylic acid (5-SSA) complexes. The formed binary complex species are ML, MLH and ML2 and obtained skewness values range from -0.15-0.71 for CoII, -0.27-0.32 for Ni” and -0.41-0.32 for CuII describes the distribution curves are left skewed and right skewed. The peak of the distribution curves shows platykurtic and leptokurtic with regards to the obtained values ranging from 2.89-6.14.
Conclusion:
It is observed that there is a significant influence of co-solvent, Dimethyl Sulfoxide (DMSO)-water mixtures on the stability constants of metal-ligand complexes, also studied how some factors such as changes in concentrations of ligand, acid, base log F and volume of the solution have influence on the protonation constants.
Background:
Chrozophora rottleri (Geiseler) A. Juss. ex Spreng. is a well-known traditional medicinal plant with a complex biological profile, though inadequate research has been established on its possible anti-diabetic effects and active metabolite profiling. In the present work, Methanolic leaf extracts (MECR) was used to identify plant metabolites by HR-LCMS analysis, and in silico docking studies and screened to assess their hypoglycaemic potential.
Materials and Methods:
In the preliminary investigation, the druggable abilities of the compounds were examined using the Swiss ADME in silico tool. The phytochemicals were virtually evaluated to determine their binding efficacies against the following proteins: sodium-glucose co-transporter 1 (PDB ID: 5EQG), insulin receptor (PDB ID: 1IR3), glucose co-tra ns porter 1 (PDB ID: 3DH4), and human dipeptidyl peptidase-IV (DPP-IV) (PDB ID: 4A5S). Besides, the impact of MECR on oxidative stress was evaluated by DPPH, H2O2, and FRAP assays.
Results:
In the HR-LCMS analysis, a total of 31 phytochemicals were found, including 14 flavonoids, 7 glycosides, 3 phenols, and a few carbohydrates, fatty acids, and alkaloids. Most phytochemicals showed favourable oral bioavailability and druggable characteristics, with 0 or 1 violation of Lipinski’s criteria. In contrast to dapagliflozin, a flavonoid compounds remikiren (AA12) and aureusidin (AA11); and an isoflavone genistein 8-C-glucoside (AA6) demonstrated greater affinity for 5EQG in docking study. A phenolic compound, cryptochlorogenic acid (AA1), had a notably higher binding affinity for 4A5S in comparison to vildagliptin.
Conclusion:
The present work has undertaken the first-ever investigation of bioactive phytochemicals and in silico hypoglycaemic profiling of leaves of C. rottleri. It can provide insight into further research for the discovery of new potential anti-diabetic agents.
Background:
Over 50% of the population in Malaysia has hypercholesterolemia, which puts them at a high risk of cardiovascular disease. Both food sources and the ingredients in traditional medications are essential to the treatment of this ailment. Seaweeds are naturally occurring dietary bioresources that have garnered a lot of attention recently. The local seaweed Kappaphycus striatus (K. striatus) contains numerous beneficial phytoconstituents that have the potential to serve as new drug candidates due to their health benefits. Thus, the aim of the study was to analyze and characterize the phytoconstituents present in the K. striatus.
Materials and Methods:
Extraction was carried out by a simple maceration method. The analysis of phytoconstituents was carried out via GCMS, HPLC, and LCMS methods. The GCMS chromatogram of the components were compared with the database of known components from the GC-MS NIST (2008) library, whereas the LCMS chromatographic profiles were analyzed based on the accurate mass data identified, and the predicted compounds were annotated using the METLIN database.
Results:
HPLC analysis profiling shows the presence of most of the polar phytoconstituents. LCMS and GCMS analysis results identified and characterize different types of bioactive compounds in the methanolic extract of K. striatus. Some of the compounds have been identified as potential anti-hypertensive and anti-hypercholesterolemia agents, as reported in previous studies.
Conclusion:
We conclude that the precise identification is crucial for understanding the potential pharmacological activities of these compounds. The effectiveness of K. striatus phytoconstituents in treating hypercholesterolemia requires additional validation through in vivo research. These discoveries highlight the potential of K. striatus as a significant source of therapeutic agents and lay the foundation for the development of novel medications for treatment of hypertension and hypercholesterolemia.
Background:
Nirmatrelvir and Ritonavir are used in combination (Paxlovid®) in order to treat COVID-19. Thus, the goal of the current study was to create an easy-to-use, accurate, and sensitive method for the preparation of nanosponges utilising High-Performance Liquid Chromatography (HPLC) to simultaneously estimate Nirmatrelvir and Ritonavir in plasma samples and prepared nanosponges.
Materials and Methods:
Nanosponges containing Nirmatrelvir and Ritonavir were prepared using ethyl-cellulose. Formulated Nanosponges are useful to increase the safety and efficacy of Nirmatrelvir and Ritonavir combinational therapy and also support Therapeutic Drug Monitoring (TDM). Patients are presently advised not to use Paxlovid® because of the challenging TDM but who are most likely to become really ill from COVID-19 infections should benefit from these nanosponges.
Results:
The proposed method’s validation was conducted in accordance with ICH recommendations Q2R1, demonstrating its good linearity and accuracy, and precision. We saw from the selectivity studies that the retention durations of the medications under investigation did not exhibit any additional peaks. 89.63% w/w and 89.98% w/w, respectively, were computed as the entrapment efficiency of nanosponges for Nirmatrelvir and Ritonavir, using the established method to determine their entrapment efficiency in formed nanosponges. With correlation coefficient (R2) values of 0.998 and 0.996, respectively, the observed concentration in plasma linearity for Ritonavir was 2842 ng/mL to 24550 ng/mL and for Nirmatrelvir was 2791 ng/ mL to 25414 ng/mL.
Conclusion:
The new approach showed that both medications were stable over the course of the trial and the three freeze-thaw cycles.
Aim:
The study in Northern Cyprus aimed to improve patient-centered care and healthcare practices by examining community perceptions of Herbal Products (HPs) for liver and biliary diseases.
Materials and Methods:
The self-administered questionnaire utilized in this cross-sectional study, which was carried out in Nicosia, Northern Cyprus from October 2021 to July 2022, allowed 446 participants to provide information on their sociodemographic characteristics and attitudes toward HPs.
Results:
It was observed that liver diseases are common in Northern Cyprus, with 48.2% suffering from some form. HP use was determined at 47.8%. Pharmacies were the most commonly sought-after sources of information at all education levels, followed by physicians. Camellia sinensis was the most commonly consumed plant, followed by Cynara scolymus, Curcuma longa, Taraxacum officinale and Glycyrrhiza glabra. On the other hand, Silybum marianum was unpreferred.
Conclusion:
The knowledge of both the healthcare profession (physicians, pharmacists, etc.) and the community in Northern Cyprus need to be improved on the HPs, however, there exists the need for more studies, and instruction on HPs with particular emphasis on safety.
Background:
This study explores the perspectives of Northern Cyprus (NC) pharmacists, physicians, dieticians, and the public regarding Herbal Products (HP) for Weight Control (WC) and slimming, contributing valuable insights to healthcare practices and public awareness.
Aims:
The objective is to comprehensively assess the knowledge, attitudes, and practices of community pharmacists, physicians/dieticians, and the general public in NC concerning WC and slimming. Additionally, the study aims to investigate their essential roles in dispensing HP for weight management, to enhance the safe and efficient use of herbal medicinal products and raise awareness about their effectiveness.
Materials and Methods:
The study involved 303 participants from the public, 24 pharmacists, and 21 physicians/dieticians who voluntarily participated through a combination of face-to-face and online distribution. Administering three questionnaires, the collected responses underwent statistical analysis using SPSS software. Results: Among public respondents, 71.95% reported not using HP for WC. For users, Senna was the preferred choice for 57.32%, followed by green tea at 51.22%. Pharmacists recommended Senna (58.33%) and green tea (50.00%) to their patients. Physicians/dieticians exhibited equal preferences, with 52.38% recommending green tea and Senna.
Conclusion:
Pharmacists play an essential role in raising awareness and educating patients on the safe utilization of HP for WC. However, a notable gap in their education regarding safe use, interactions, and side effects hinders optimal counseling and care. This study underscores the urgency for enhanced education and resources to address this knowledge deficit among pharmacists, healthcare professionals, and the public in NC.
Background:
The liver serves a variety of essential purposes, making it the most important organ. Chronic liver disease (CLD) has a wide range of etiologies, including toxins, alcoholism, infections, autoimmune illnesses, and hereditary problems. Patients are initially asymptomatic, as the disease progresses, signs like jaundice, icterus, pedal oedema, and abdominal distension can be seen. Liver functioning tests are used to assess liver disease progression. Liver disease may result in problems such as portal vein hypertension (PH). The treatment is to stop the disease and its associated complications from getting worse. For the treatment, a comprehensive strategy involving hepatoprotectives and antibacterial medications is required.
Materials and Methods:
This is a prospective observational study with the sample size of 200 patients. Patients were selected by simple random sampling. Then the patients were categorized according to their disease condition and collected data was analysed using suitable methods.
Results:
According to our research, chronic alcoholics have a higher risk of getting hepatitis and alcoholic fatty liver disease. The greatest treatment for liver disease is alcohol abstinence, which can be started as soon as possible. Avoiding alcohol will increase survival at all stages of the illness. Thiamine and ursodeoxycholic acid are the two hepatoprotectives that are most usually advised, followed by rifaximin and L-ornithine and L-aspartate (LOLA).
Conclusion:
Our research found that within the first week of treatment, serum bilirubin levels, aspartate transaminase levels, and alanine transaminase levels significantly decreased in people receiving hepatoprotective medications. The pharmacist is crucial for better therapeutic management based on the patient’s stage and condition.
Objectives:
Moxifloxacin hydrochloride is an antibiotic related to flouroquinolones class. It possessed reasonable to exceptional efficacy against gram-negative ocular pathogens. The prime goal of this study was to formulate and estimate moxifloxacin hydrochloride entrapped microsponge in situ gel to treat conjunctivitis.
Materials and Methods:
Moxifloxacin hydrochloride loaded microsponges was manufactured using modified emulsion-solvent dispersion technique. Optimized microsponge group was integrated into Carbopol base after in vitro characterization to formulate 1% moxifloxacin hydrochloride entrapped microsponge gel. Then, the prepared gel was examined for ocular irritancy, isotonicity, sterility testing, antimicrobial activity. Drug deposition ability and in vivo efficacy of above optimized batch was compared with marketed preparation in rabbit eye with conjunctivitis.
Results:
The mean particle size and ex vivo release of drug from optimized microsponge formulation was depicted to be 4.83±0.26 |jm and 75.80±1.5 at the ending of 24 hr and entrapment was found to be 85.51±0.74%. SEM study evidenced the porous, spherical morphology of microsponges whereasFT-IR confirmed the microsponges’ formation. No irritation in eye was observed with moxifloxacin hydrochloride microsponge in animals.
Conclusion:
It was concluded that moxifloxacin hydrochloride entrapped microsponge have shown augmented penetration of drug and in situ gel enhance the exposure time of drug loaded microsponges and conjunctiva of eye. Thus, moxifloxacin hydrochloride encapsulated microsponge gel can be investigated further as a medication to cure conjunctivitis.
Aim/Background:
Cervical cancer is a common gynecologic malignant tumor, its occurrence and development are related to genetic and environmental factors. Recent studies have shown that Programmed Cell Death 4 (PDCD4) and Transcription Factor EB (TFEB) plays crucial roles in the pathogenesis of cervical cancer. The interaction between PDCD4 and TFEB and their regulatory mechanism on cellular functions in cervical cancer have not been fully explored.
Materials and Methods:
Therefore, this study utilized the Hela cell line as a cervical cancer model to investigate the changes in TFEB expression levels and the proliferation, migration, invasion and EMT processes of cervical cancer cells through the silencing of PDCD4. Real-time quantitative PCR and Western blot were employed to assess the expression levels of PDCD4 and TFEB, while CCK-8, scratch assay, Transwell invasion assay and Western blot were used to evaluate changes in cell proliferation, migration, invasion capabilities and EMT processes.
Results:
The experimental results demonstrated that silencing PDCD4 significantly increased the expression level of TFEB. Simultaneously, silencing PDCD4 also significantly accelerated the proliferation rate of Hela cells, enhanced the cells’ migration, invasion capabilities and promoted the EMT processes. Further experimental results showed that silencing TFEB could partially reverse the promoting effects of PDCD4 silencing on cell proliferation, migration and invasion. In cervical cancer, silencing PDCD4 can lead to TFEB overexpression, thereby promoting the proliferation, migration and invasion of Hela cells.
Conclusion:
These findings provide crucial clues for the in-depth study of molecular mechanisms in cervical cancer and indicate that the PDCD4-TFEB pathway could potentially serve as a target for the treatment and prevention of this disease.
Background:
Developing effective antimalarial medications requires understanding the interactions between Plasmodium Dihydroorotate dehydrogenase (DHOdehase) and Artemisinin, including its fourteen stereoisomers (R/S) which have distinct pharmacological effects due to seven chiral centres.
Materials and Methods:
Computational techniques, including molecular docking and network pharmacology, were used to generate and analyse Artemisinin’s stereoisomers. The binding strength and durability of the interactions between the stereoisomers and DHOdehase were examined. STRING DB network analysis and pathway enrichment analysis were conducted to identify functional partners and biological pathways associated with DHOdehase.
Results:
The study identified C6 and C8 positions of Artemisinin’s stereoisomers as potential binding sites with DHOdehase, showing negative binding energies of -8.7 and -8.2 kcal/mol, respectively. The ligand-protein interactions included hydrogen bonds, Van der Waals forces, Pi-Sigma, alkyl/Pi-alkyl and carbon-hydrogen bonds. STRING DB network analysis revealed DHOdehase interactions with 10 functional partner proteins with confidence scores between 0.889 and 0.999. Pathway enrichment analysis linked DHOdehase to pyrimidine metabolism (KEGG term map00240). Additionally, Isothermal Titration Calorimetry (ITC) demonstrated higher affinity parameters for Artemisinin and its stereoisomer Artesunate.
Conclusion:
The molecular docking, ITC results and network analysis provide insights into the interaction and pharmacological profiles of Artemisinin stereoisomers, laying the groundwork for experimental validation and the development of more effective antimalarial treatments.
Introduction
Sophoridine, an alkaloid compound which is isolated from various plant species like Sophoraalopecuroides and Sophora flavescens. It identified to have potential pharmacological properties, including anti-inflammatory, anticancer and antiviral activities. The effect of the sophoridine on mTOR and NOTCH1 pathways that are critical in NSCLC is not well understood.
Materials and Methods
In order to assess the virtual interaction of mTOR and NOTCH1 with sophoridine, we employed molecular docking. We also performed an in vitro analysis using the NSCLC cell line (A549) using MTT, RT-PCR, western blot and wound healing assays.
Results and Discussion
We report strong interaction of sophoridine with mTOR and it exhibited cytotoxic effect on NSCLC cells, causing downregulation of the mTOR and NOTCH1 genes. We used a wound-healing assay to assess its impact on cell migration in NSCLC cells and our findings confirmed that sophoridine significantly (p = 0.0265) inhibits cell migration in A549 cells.
Conclusion
Our study indicates sophoridine to be potential anti-cancer drug in NSCLC cell via inhibition of mTOR and NOTCH1 axis.