-
Ultrasonics Sonochemistry May 2024The utilization of metallic nanoparticles in bio-nanofabrication holds significant potential in the field of applied research. The current study applied and compared...
UPLC-qTOF-MS phytochemical profile of Commiphora gileadensis leaf extract via integrated ultrasonic-microwave-assisted technique and synthesis of silver nanoparticles for enhanced antibacterial properties.
The utilization of metallic nanoparticles in bio-nanofabrication holds significant potential in the field of applied research. The current study applied and compared integrated ultrasonic-microwave-assisted extraction (US/MICE), ultrasonic extraction (USE), microwave-assisted extraction (MICE), and maceration (MAE) to extract total phenolic content (TPC). In addition, the study examined the antioxidant activity of Commiphora gileadensis (Cg) leaf. The results demonstrated that the TPC of US/MICE exhibited the maximum value at 59.34 ± 0.007 mg GAE/g DM. Furthermore, at a concentration of 10 μg/mL, TPC displayed a significant scavenging effect on DPPH (56.69 %), with an EC (6.48 μg/mL). Comprehensive metabolite profiling of the extract using UPLC-qTOF-MS/MS was performed to identify active agents. A total of 64 chromatographic peaks were found, out of which 60 were annotated. The most prevalent classes of metabolites found were polyphenols (including flavonoids and lignans), organic compounds and their derivatives, amides and amines, terpenes, and fatty acid derivatives. Transmission electron microscopy (TEM) revealed the aggregate size of the synthesized nanoparticles and the spherical shape of C. gileadensis-mediated silver nanoparticles (Cg-AgNPs). The nanoparticles had a particle size ranging from 7.7 to 42.9 nm. The Cg-AgNPs exhibited more inhibition zones against S. aureus and E. coli. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Cg-extract, AgNPs, and Cg-AgNPs were also tested. This study demonstrated the feasibility of using combined ultrasonic-microwave-assisted extraction to separate and extract chemicals from C. gileadensis on a large scale. These compounds have potential use in the pharmaceutical industry. Combining antibacterial and biocompatible properties in materials is vital for designing new materials for biomedical applications. Additionally, the results showed that the biocompatibility of the Ag-NPs using C. gileadensis extracts demonstrated outstanding antibacterial properties.
PubMed: 38815489
DOI: 10.1016/j.ultsonch.2024.106923 -
Acta Pharmaceutica (Zagreb, Croatia) Jun 2024Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its...
Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its emptying kinetics. The purpose of this study was thus to simulate different individual water gastric emptying (GE) patterns in an glass-bead flow-through dissolution system. Further, the effect of GE on the dissolution of model drugs from immediate-release tablets was assessed by determining the amount of dissolved drug in the samples pumped out of the stomach compartment. Additionally, different HCl solutions were used as dissolution media to assess the effect of the variability of pH of the gastric fluid on the dissolution of three model drugs: paracetamol, diclofenac sodium, and dipyridamole. The difference in fast and slow GE kinetics resulted in different dissolution profiles of paracetamol in all studied media. For diclofenac sodium and dipyridamole tablets, the effect of GE kinetics was well observed only in media, where the solubility was not a limiting factor. Therefore, GE kinetics of co-ingested water influences the drug release from immediate-release tablets, however, in certain cases, other parameters influencing drug dissolution can partly or fully hinder the expression of this effect.
Topics: Gastric Emptying; Drug Liberation; Diclofenac; Water; Solubility; Tablets; Dipyridamole; Acetaminophen; Hydrogen-Ion Concentration; Kinetics; Administration, Oral; Glass
PubMed: 38815199
DOI: 10.2478/acph-2024-0016 -
PloS One 2024The prevalence of gastrointestinal tumors continues to be significant. To uncover promising therapeutic targets for these tumors, we rigorously executed a Mendelian...
BACKGROUND
The prevalence of gastrointestinal tumors continues to be significant. To uncover promising therapeutic targets for these tumors, we rigorously executed a Mendelian randomization (MR) study to comprehensively screen the blood metabolomes for potential causal mediators of five frequently encountered gastrointestinal tumors (Liver Cancer, Colorectal Cancer, Esophageal Cancer, Gastric Cancer and Pancreatic Cancer).
METHODS
We selected a comprehensive set of 137 distinct blood metabolites derived from three large-scale genome-wide association studies (GWASs) involving a total of 147827 participants of European ancestry. The gastrointestinal tumors-related data were obtained from a GWAS conducted within the Finnish study. Through meticulous MR analyses, we thoroughly assessed the associations between blood metabolites and gastrointestinal tumors. Additionally, a phenome-wide MR (Phe-MR) analysis was employed to investigate the potential on-target side effects of metabolite interventions.
RESULTS
We have identified 1 blood metabolites, namely isovalerylcarnitine (ORlog10: 1.01; 95%CI, 1.01-1.02; P = 1.81×10-7), as the potential causal mediators for liver cancer. However, no potential pathogenic mediators were detected for the other four tumors.
CONCLUSIONS
The current systematic MR analysis elucidated the potential role of isovalerylcarnitine as a causal mediator in the development of liver cancer. Leveraging the power of Phe-MR study facilitated the identification of potential adverse effects associated with drug targets for liver cancer prevention. Considering the weighing of pros and cons, isovalerylcarnitine emerges as a promising candidate for targeted drug interventions in the realm of liver cancer prevention.
Topics: Humans; Gastrointestinal Neoplasms; Metabolome; Genome-Wide Association Study; Mendelian Randomization Analysis; Male; Female; Finland; Carnitine; Middle Aged; Risk Factors; Liver Neoplasms
PubMed: 38814898
DOI: 10.1371/journal.pone.0304574 -
International Journal of Chronic... 2024Real-life research is needed to evaluate the effectiveness of budesonide/glycopyrrolate/formoterol (BGF) in routine COPD primary care management. We assessed the... (Observational Study)
Observational Study
PURPOSE
Real-life research is needed to evaluate the effectiveness of budesonide/glycopyrrolate/formoterol (BGF) in routine COPD primary care management. We assessed the frequency of medication success among patients with COPD who initiated BGF using real-world data.
PATIENTS AND METHODS
Patients with a recorded diagnostic COPD code who started BGF with ≥2 prescriptions within 90-days were identified in the UK Optimum Patient Care Research Database and followed from first prescription until censoring at the end of follow-up (180-days), death, leaving database or end of data at 24/10/2022. The primary outcome was medication success at 90-days post-BGF initiation, defined as no major cardiac or respiratory event (ie no complicated COPD exacerbation, hospitalization for any respiratory event, myocardial infarction, new/hospitalized heart failure, and death) and no incidence of pneumonia. Medication success was also assessed at 180-days post-BGF initiation. Overall real-life medication success was claimed if the lower 95% confidence interval (CI) for the proportion of patients meeting the primary outcome was ≥70% (defined a priori).
RESULTS
Two hundred eighty-five patients were included. Prior to BGF initiation, these patients often had severe airflow obstruction (mean ppFEV: 54.5%), were highly symptomatic (mMRC ≥2: 77.9% (n = 205/263); mean CAT score: 21.7 (SD 7.8)), with evidence of short-acting β-agonist (SABA) over-use (≥3 inhalers/year: 62.1%, n=179/285), repeat OCS prescriptions (≥2 courses/year: 33.0%, n = 95/285) and multiple primary care consultations (≥2 visits/year: 61.1%, n = 174/285). Overall, 39.6% of patients (n = 113/285) switched from previous triple therapies. Real-life medication success was achieved by 96.5% of patients (n = 275/285 [95% CI: 93.6, 98.3]) during 90-days treatment with BGF and by 91.8% (n = 169/184 [95% CI: 86.9, 95.4]) of patients at 180-days. The prescribed daily dose of SABA remained stable over the study period.
CONCLUSION
The majority of patients initiating BGF experienced real-life medication success reflecting the absence of severe cardiopulmonary events. These benefits were apparent after 90-days of treatment and sustained over 180-days.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Male; Female; Aged; Primary Health Care; Treatment Outcome; Bronchodilator Agents; Middle Aged; Time Factors; Adrenergic beta-2 Receptor Agonists; United Kingdom; Glycopyrrolate; Databases, Factual; Budesonide, Formoterol Fumarate Drug Combination; Lung; Muscarinic Antagonists; Drug Combinations; Retrospective Studies; Glucocorticoids; Aged, 80 and over
PubMed: 38813078
DOI: 10.2147/COPD.S452624 -
RSC Advances May 2024Yellow wine lees, a by-product produced while brewing yellow wine, can be a helpful biomass resource through pyrolysis. However, there have been very few studies on the...
Yellow wine lees, a by-product produced while brewing yellow wine, can be a helpful biomass resource through pyrolysis. However, there have been very few studies on the pyrolysis of yellow wine lees. The kinetics and mechanism of pyrolysis in yellow wine lees were explored through an extensive study of their chemical and elemental composition. The pyrolysis mechanism of yellow wine lees was further studied using thermogravimetric analysis (TGA) from 30 °C to 900 °C. The TG/DTG analysis showed that yellow wine lees thermally decomposed mainly between 121 °C and 500 °C. The maximum decomposition was observed between 218 °C and 326 °C, with a clear peak at 298 °C. Upon analyzing the 3D-FTIR results, the gas phase products at this stage primarily included inorganic molecules like CO, HO, and CH, along with organic compounds such as esters, alcohols, phenols, amines, ethers, aldehydes, ketones, and acids. The Maillard reaction and ketosis decarboxylation primarily occurred in proteins (amino acids) and carbohydrates. The pyrolysis kinetics of yellow wine lees were analyzed utilizing the distributed activation energy model (DAEM). The results of DAEM were simultaneously verified using the Flynn-Wall-Ozawa (FWO) method. The findings indicated that the pyrolysis of yellow wine lees conforms to the assumptions of infinite parallel reactions and activation energy distribution. As the conversion rate increased during pyrolysis, the activation energy of yellow wine lees initially increased to 210-220 kJ mol, then stabilized at 190-200 kJ mol and rapidly decreased to approximately 100 kJ mol. This study offers a theoretical basis for the application of yellow wine lees using pyrolysis.
PubMed: 38812961
DOI: 10.1039/d4ra01541j -
Frontiers in Microbiology 2024is a member of the that inhabits a variety of niches and is found in all climates. Bacteria from the genus can cause soft rot disease on various plants due to the...
INTRODUCTION
is a member of the that inhabits a variety of niches and is found in all climates. Bacteria from the genus can cause soft rot disease on various plants due to the secretion of plant cell wall degrading enzymes (PCWDEs). The species is responsible for the vascular necrosis of sugar beet and soft rot of many vegetables. It also infects sunflowers and artichokes. The main sugar present in sugar beet is sucrose while xylose is one of the main sugars in artichoke and sunflower.
METHODS
In our work, we applied studies coupled with genomics to investigate the metabolism of in the presence of xylose and sucrose as the only carbon source. The ability of the strains to use various sugars as the only carbon source were confirmed by the polypyridyl complex of Ru(II) method in 96-well plates.
RESULTS
Our studies provided information on the metabolic pathways active during the degradation of those substrates. It was observed that different metabolic pathways are upregulated in the presence of xylose in comparison to sucrose.
DISCUSSION
The presence of xylose enhances extracellular metabolism of sugars and glycerol as well as stimulates EPS and IPS synthesis. In contrast, in the presence of sucrose the intensive extracellular metabolism of amines and amino acids is promoted.
PubMed: 38812674
DOI: 10.3389/fmicb.2024.1323765 -
Turkish Journal of Medical Sciences 2024In this study, it was aimed to retrospectively compare the effect of greater occipital nerve (GON) block performed with ultrasonography using low (0.3%) and high (0.5%)... (Comparative Study)
Comparative Study
BACKGROUND/AIM
In this study, it was aimed to retrospectively compare the effect of greater occipital nerve (GON) block performed with ultrasonography using low (0.3%) and high (0.5%) concentrations of bupivacaine on pain scores and patient satisfaction in chronic migraine (CM).
MATERIALS AND METHODS
The mean number of days with pain, the mean duration of pain in the attacks, and the highest numerical rating scale (NRS) scores recorded in the 1 month preblock and 1 and 3 months postblock of 80 patients (40 for Group 1, 0.3% bupivacaine; 40 for Group 2, 0.5% bupivacaine) who underwent ultrasonography-guided GON block were recorded from the patient file data. According to the protocol applied by our clinic, GON block was applied to each patient 6 times with the same procedures, in total.
RESULTS
While there was a statistically significant difference between the groups in terms of the number of days with pain and the maximum NRS score in the 1-month preblock evaluation (p = 0.01, p < 0.001), at 3 months postblock, no statistical difference was observed in terms of the number of days with pain, duration of pain, or NRS score (p = 0.961, p = 0.108, and p = 0.567). In the intragroup evaluations, at 3 months postblock, the number of days with pain decreased from 17.5 days to 7 days in Group 1 and from 24.0 days to 8.0 days in Group 2. The duration of pain and maximum NRS values were statistically significantly decreased in the intragroup evaluation in both groups pre and postblock.
CONCLUSION
Complications arising from the procedure and the local anesthetic used are essential points to consider in applying GON block. In CM treatment using GON block application, a similar effect to the standard local anesthetic application (0.5%) can be achieved by administering local anesthetic at a lower dose (0.3%).
Topics: Humans; Bupivacaine; Female; Migraine Disorders; Male; Adult; Nerve Block; Anesthetics, Local; Retrospective Studies; Ultrasonography, Interventional; Middle Aged; Treatment Outcome; Pain Measurement; Chronic Disease; Patient Satisfaction
PubMed: 38812648
DOI: 10.55730/1300-0144.5782 -
Journal of Integrative Neuroscience May 2024Methamphetamine (METH) is a highly addictive drug that directly affects the central nervous system. METH use not only harms the user's health but also poses risks and...
BACKGROUND
Methamphetamine (METH) is a highly addictive drug that directly affects the central nervous system. METH use not only harms the user's health but also poses risks and costs to society. Prolonged METH dependence has been shown to impair cognition, which may be the primary factor in impulsive drug-seeking behaviors and high relapse rates. However, the molecular mechanisms underlying METH addiction and METH-induced cognitive decline remain poorly understood.
METHODS
To illuminate the potential molecular mechanisms underpinning METH addiction, we compared serum protein expression levels between 12 long-term METH users and 12 healthy controls using label-free quantitative proteomics. Bioinformatic analyses were conducted to determine functional networks and protein-protein interactions.
RESULTS
In total, 23 differentially expressed proteins were identified between the two groups. The differentially expressed proteins were related to cognitive dysfunction, neuroinflammation, immune impairment, metabolic disturbances, and calcium binding and regulation.
CONCLUSIONS
These 23 proteins may underpin the multi-system damage induced by chronic METH exposure. Our findings provide novel insights into the molecular basis of METH addiction and inform potential prevention and treatment strategies for individuals with METH dependence.
Topics: Humans; Amphetamine-Related Disorders; Male; Methamphetamine; Cognitive Dysfunction; Adult; Proteomics; Central Nervous System Stimulants; Female; Young Adult
PubMed: 38812388
DOI: 10.31083/j.jin2305107 -
Frontiers in Bioscience (Landmark... May 2024Choline participates in three major metabolic pathways: oxidation, phosphorylation, and acetylation. Through oxidation, choline is converted to betaine and contributes... (Review)
Review
Choline participates in three major metabolic pathways: oxidation, phosphorylation, and acetylation. Through oxidation, choline is converted to betaine and contributes to methyl metabolism and epigenetic regulation. Through phosphorylation, choline participates in phospholipid metabolism, and serves as the precursor of phosphocholine, phosphatidylcholine, glycerophosphocholine, and other essential compounds, thereby modulating lipid metabolism and transport. Through acetylation, choline is transformed into acetylcholine in cholinergic neurons, playing a vital role in neurotransmission. Moreover, gut microbiota can metabolize choline into trimethylamine-N-oxide, and be involved in the pathogenesis of various diseases such as nonalcoholic fatty liver disease (NAFLD), cancer, cardiovascular disease, etc. Since choline metabolism is implicated in the development of NAFLD and diverse cancers, including liver cancer, it may serve as a therapeutic target for these diseases in the future. Currently, there are numerous therapeutic agents targeting choline metabolism to treat NAFLD and cancers, but most of them are ineffective and some even have adverse effects that lead to a series of complications. Therefore, further research and clinical validation are required to obtain safe and efficacious drugs. This review comprehensively summarizes the choline metabolic pathway and its regulatory mechanisms, elucidates the roles and mechanisms of choline metabolism in the aforementioned diseases, and provides a discussion of the current advances and immense potential of this field.
Topics: Humans; Choline; Non-alcoholic Fatty Liver Disease; Animals; Gastrointestinal Microbiome; Neoplasms; Liver Neoplasms; Lipid Metabolism
PubMed: 38812309
DOI: 10.31083/j.fbl2905182 -
Journal of Biomedical Science May 2024Severe infection and sepsis are medical emergencies. High morbidity and mortality are linked to CNS dysfunction, excessive inflammation, immune compromise, coagulopathy... (Review)
Review
Severe infection and sepsis are medical emergencies. High morbidity and mortality are linked to CNS dysfunction, excessive inflammation, immune compromise, coagulopathy and multiple organ dysfunction. Males appear to have a higher risk of mortality than females. Currently, there are few or no effective drug therapies to protect the brain, maintain the blood brain barrier, resolve excessive inflammation and reduce secondary injury in other vital organs. We propose a major reason for lack of progress is a consequence of the treat-as-you-go, single-nodal target approach, rather than a more integrated, systems-based approach. A new revolution is required to better understand how the body responds to an infection, identify new markers to detect its progression and discover new system-acting drugs to treat it. In this review, we present a brief history of sepsis followed by its pathophysiology from a systems' perspective and future opportunities. We argue that targeting the body's early immune-driven CNS-response may improve patient outcomes. If the barrage of PAMPs and DAMPs can be reduced early, we propose the multiple CNS-organ circuits (or axes) will be preserved and secondary injury will be reduced. We have been developing a systems-based, small-volume, fluid therapy comprising adenosine, lidocaine and magnesium (ALM) to treat sepsis and endotoxemia. Our early studies indicate that ALM therapy shifts the CNS from sympathetic to parasympathetic dominance, maintains cardiovascular-endothelial glycocalyx coupling, reduces inflammation, corrects coagulopathy, and maintains tissue O supply. Future research will investigate the potential translation to humans.
Topics: Humans; Sepsis; Adenosine; Lidocaine; Magnesium; Fluid Therapy
PubMed: 38811967
DOI: 10.1186/s12929-024-01043-4