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Plants (Basel, Switzerland) Apr 2022Free radicals play a critical role in the chemical processes that occur in all cells. Pharmaceutical companies manufacture a variety of synthetically prepared...
Free radicals play a critical role in the chemical processes that occur in all cells. Pharmaceutical companies manufacture a variety of synthetically prepared antioxidants, but it is known that many of these can be carcinogenic. As a result, efforts are being made to find natural antioxidants that do not have these side effects. Lichens may be suitable candidates because they contain secondary metabolites with proven antioxidant properties. This could be explained by the presence of compounds with phenolic groups in lichens. The radical scavenging reaction is a chemical reaction governed by stoichiometry, and our aim is to determine the efficacy of these reactions. The aim of this study is to compare metabolite activity based on the same amount of substance involved in radical scavenging, calculated in micromoles rather than weight concentration. This provides an accurate way of comparing radical scavenging activity. We tested superoxide anion scavenging activity and free radical scavenging activity of isolated lichen secondary metabolites and their mixtures in different ratios. The following compounds were isolated and tested for antioxidant activity: gyrophoric acid (), evernic acid (), physodic acid, 3-hydroxyphysodic acid, physodalic acid and atranorin (), and usnic acid (as a synthetic compound). Of all the tested compounds, 3-hydroxyphysodic acid, as well as mixtures containing this metabolite, showed the strongest scavenging activity. The results also demonstrated that calculation by amount of substance leads to a new consideration of antioxidant activity.
PubMed: 35448805
DOI: 10.3390/plants11081077 -
Molecules (Basel, Switzerland) Mar 2022Adenosine triphosphate (ATP) is the key energy intermediate of cellular metabolic processes and a ubiquitous extracellular messenger. As an extracellular messenger, ATP... (Review)
Review
Adenosine triphosphate (ATP) is the key energy intermediate of cellular metabolic processes and a ubiquitous extracellular messenger. As an extracellular messenger, ATP acts at plasma membrane P2 receptors (P2Rs). The levels of extracellular ATP (eATP) are set by both passive and active release mechanisms and degradation processes. Under physiological conditions, eATP concentration is in the low nanomolar range but can rise to tens or even hundreds of micromoles/L at inflammatory sites. A dysregulated eATP homeostasis is a pathogenic factor in several chronic inflammatory diseases, including type 2 diabetes mellitus (T2DM). T2DM is characterized by peripheral insulin resistance and impairment of insulin production from pancreatic β-cells in a landscape of systemic inflammation. Although various hypoglycemic drugs are currently available, an effective treatment for T2DM and its complications is not available. However, counteracting systemic inflammation is anticipated to be beneficial. The postulated eATP increase in T2DM is understood to be a driver of inflammation via P2X7 receptor (P2X7R) activation and the release of inflammatory cytokines. Furthermore, P2X7R stimulation is thought to trigger apoptosis of pancreatic β-cells, thus further aggravating hyperglycemia. Targeting eATP and the P2X7R might be an appealing novel approach to T2DM therapy.
Topics: Adenosine Triphosphate; Cytokines; Diabetes Mellitus, Type 2; Humans; Inflammation; Signal Transduction
PubMed: 35335211
DOI: 10.3390/molecules27061838 -
Antioxidants (Basel, Switzerland) Feb 2022Vitamin C is a powerful antioxidant and facilitates neurotransmission. This study explored association between vitamin C deficiency and cognitive impairment in older...
Vitamin C is a powerful antioxidant and facilitates neurotransmission. This study explored association between vitamin C deficiency and cognitive impairment in older hospitalised patients. This prospective study recruited 160 patients ≥ 75 years admitted under a Geriatric Unit in Australia. Cognitive assessment was performed by use of the Mini-Mental-State-Examination (MMSE) and patients with MMSE scores <24 were classified as cognitively-impaired. Fasting plasma vitamin C levels were determined using high-performance-liquid-chromatography. Patients were classified as vitamin C deficient if their levels were below 11 micromol/L. Logistic regression analysis was used to determine whether vitamin C deficiency was associated with cognitive impairment after adjustment for various covariates. The mean (SD) age was 84.4 (6.4) years and 60% were females. A total of 91 (56.9%) were found to have cognitive impairment, while 42 (26.3%) were found to be vitamin C deficient. The mean (SD) MMSE scores were significantly lower among patients who were vitamin C deficient (24.9 (3.3) vs. 23.6 (3.4), p-value = 0.03). Logistic regression analysis suggested that vitamin C deficiency was 2.9-fold more likely to be associated with cognitive impairment after adjustment for covariates (aOR 2.93, 95% CI 1.05−8.19, p-value = 0.031). Vitamin C deficiency is common and is associated with cognitive impairment in older hospitalised patients.
PubMed: 35326113
DOI: 10.3390/antiox11030463 -
Current Developments in Nutrition Mar 2022Pregnant women in Malawi are at risk of selenium deficiency, which can have adverse effects on pregnancy outcomes. Interventions for improving selenium status are needed.
Provision of Small-Quantity Lipid-Based Nutrient Supplements Increases Plasma Selenium Concentration in Pregnant Women in Malawi: A Secondary Outcome of a Randomized Controlled Trial.
BACKGROUND
Pregnant women in Malawi are at risk of selenium deficiency, which can have adverse effects on pregnancy outcomes. Interventions for improving selenium status are needed.
OBJECTIVES
To assess the effect of provision of small-quantity lipid-based nutrient supplements (SQ-LNSs) to Malawian women during pregnancy on their plasma selenium concentrations at 36 wk of gestation.
METHODS
Pregnant women (≤20 wk of gestation) were randomly assigned to receive daily either: ) iron and folic acid (IFA); ) multiple micronutrients (MMN; 130 µg selenium per capsule); or ) SQ-LNS (130 µg selenium/20 g). Plasma selenium concentrations were measured by inductively coupled plasma mass spectrometry at baseline and after ≥16 wk of intervention (at 36 wk of gestation) and compared by intervention group.
RESULTS
At 36 wk of gestation, median (quartile 1, quartile 3) plasma selenium concentrations (micromoles per liter) were 0.96 (0.73, 1.23), 0.94 (0.78, 1.18), and 1.01 (0.85, 1.28) in the IFA, MMN, and SQ-LNS groups, respectively. Geometric mean (GM) plasma selenium concentration was 5.4% (95% CI: 1.8%, 9.0%) higher in the SQ-LNS group than in the MMN group and tended to be higher than in the IFA group (+4.2%; 95% CI: 1.0%, 7.8%). The prevalence of adjusted plasma selenium concentrations <1 µmol/L was 55.1%, 57.8%, and 47.3% in the IFA, MMN, and SQ-LNS groups, respectively; it was lower in the SQ-LNS group than in the MMN group, OR = 0.44 (95% CI: 0.24, 0.83), and tended to be lower than in the IFA group, OR = 0.54 (95% CI: 0.29, 1.03). There was a significant interaction between baseline plasma selenium concentration and intervention group (= 0.003). In the lowest tertile of baseline selenium concentrations, GM plasma selenium concentration was higher, and the prevalence of low values was lower in the SQ-LNS group compared with the MMN and IFA groups at 36 wk of gestation (≤ 0.007).
CONCLUSIONS
Provision of SQ-LNS containing selenium to pregnant women can be an effective strategy for improving their selenium status.This trial was registered at clinicaltrials.gov (identifier: NCT01239693).
PubMed: 35317414
DOI: 10.1093/cdn/nzac013 -
Molecular and Cellular Biology Apr 2022Protein arginine methyltransferase (PRMT) enzymes catalyze posttranslational modifications of target proteins and are often upregulated in human cancers. In this study,...
Protein arginine methyltransferase (PRMT) enzymes catalyze posttranslational modifications of target proteins and are often upregulated in human cancers. In this study, we purified two chemical compounds from seeds of based on their ability to inhibit the enzymatic activity of PRMT5. These two compounds were identified as Pheophorbide a (PPBa) and Pheophorbide b (PPBb), two breakdown products of chlorophyll. PPBa and PPBb inhibited the enzymatic activity of both Type I and Type II PRMTs with IC values at sub micromole concentrations, inhibited the arginine methylation of histones in cells, and suppressed proliferation of prostate cancer cells. Molecular docking results predicted that PPBa binds to an allosteric site in the PRMT5 structure with a high affinity (ΔG = -9.0 kcal/mol) via hydrogen bond, ionic, and π-π stacking interactions with amino acid residues in PRMT5. Another group of natural compounds referred to as protoporphyrins and sharing structural similarity with pheophorbide also inhibited the PRMT enzymatic activity. This study is the first report on the PRMT-inhibitory activity of the tetrapyrrole macrocycles and provides useful information regarding the application of these compounds as natural therapeutic reagents for cancer prevention and treatment.
Topics: Arginine; Histones; Humans; Male; Methylation; Molecular Docking Simulation; Protein-Arginine N-Methyltransferases
PubMed: 35311588
DOI: 10.1128/mcb.00523-21 -
Veterinary Medicine and Science Mar 2022The condition of footpad is an important aspect of poultry welfare. This is a problem that plagues the poultry industry because it occurs whether birds are reared in the...
BACKGROUND/AIM
The condition of footpad is an important aspect of poultry welfare. This is a problem that plagues the poultry industry because it occurs whether birds are reared in the cage or on the floor. It is reported that feeding phytase to floor-reared broiler chicks could ameliorate footpad lesions, which is related to the reduction of litter moisture. However, some studies reported that phytase supplementation could ameliorate footpad lesions, but did not affect litter quality. Therefore, phytase supplementation may have other potential mechanisms to improve the footpad lesions. Cage-reared broiler chicks were used in this study because they had no access to litter.
MATERIAL AND METHODS
A total of 234 1-day-old broiler chicks were randomly assigned to three groups based on the initial body weight (42.22 ± 0.18 g) with six replicate cages and 13 birds (mixed sex) per cage. The experimental period was 45 days. Dietary treatments were based on a corn-soybean meal-basal diet and supplemented with 500 and 750 FTU/kg Saccharomyces pombe expressed phytase. The unit of phytase (FTU) was defined as the amount of enzyme that catalyzes the release of one micromole phosphate from phytate per minute at 37°C and pH 5.5.
RESULT AND CONCLUSION
We found that dietary supplementation of S. pombe expressed phytase could improve calcium and phosphorus digestibility and subsequent improvement in toe ash, thus ameliorating footpad lesions in broiler chicks with no access to litter.
Topics: 6-Phytase; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Chickens; Saccharomyces
PubMed: 35218318
DOI: 10.1002/vms3.745 -
EBioMedicine Feb 2022Many repurposed drugs have progressed rapidly to Phase 2 and 3 trials in COVID19 without characterisation of Pharmacokinetics /Pharmacodynamics including safety data.... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomised controlled trial of intravenous nafamostat mesylate in COVID pneumonitis: Phase 1b/2a experimental study to investigate safety, Pharmacokinetics and Pharmacodynamics.
BACKGROUND
Many repurposed drugs have progressed rapidly to Phase 2 and 3 trials in COVID19 without characterisation of Pharmacokinetics /Pharmacodynamics including safety data. One such drug is nafamostat mesylate.
METHODS
We present the findings of a phase Ib/IIa open label, platform randomised controlled trial of intravenous nafamostat in hospitalised patients with confirmed COVID-19 pneumonitis. Patients were assigned randomly to standard of care (SoC), nafamostat or an alternative therapy. Nafamostat was administered as an intravenous infusion at a dose of 0.2 mg/kg/h for a maximum of seven days. The analysis population included those who received any dose of the trial drug and all patients randomised to SoC. The primary outcomes of our trial were the safety and tolerability of intravenous nafamostat as an add on therapy for patients hospitalised with COVID-19 pneumonitis.
FINDINGS
Data is reported from 42 patients, 21 of which were randomly assigned to receive intravenous nafamostat. 86% of nafamostat-treated patients experienced at least one AE compared to 57% of the SoC group. The nafamostat group were significantly more likely to experience at least one AE (posterior mean odds ratio 5.17, 95% credible interval (CI) 1.10 - 26.05) and developed significantly higher plasma creatinine levels (posterior mean difference 10.57 micromol/L, 95% CI 2.43-18.92). An average longer hospital stay was observed in nafamostat patients, alongside a lower rate of oxygen free days (rate ratio 0.55-95% CI 0.31-0.99, respectively). There were no other statistically significant differences in endpoints between nafamostat and SoC. PK data demonstrated that intravenous nafamostat was rapidly broken down to inactive metabolites. We observed no significant anticoagulant effects in thromboelastometry.
INTERPRETATION
In hospitalised patients with COVID-19, we did not observe evidence of anti-inflammatory, anticoagulant or antiviral activity with intravenous nafamostat, and there were additional adverse events.
FUNDING
DEFINE was funded by LifeArc (an independent medical research charity) under the STOPCOVID award to the University of Edinburgh. We also thank the Oxford University COVID-19 Research Response Fund (BRD00230).
Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Benzamidines; Biomarkers; COVID-19; Drug Administration Schedule; Female; Guanidines; Half-Life; Humans; Immunophenotyping; Kaplan-Meier Estimate; Male; Middle Aged; SARS-CoV-2; Treatment Outcome; Viral Load; COVID-19 Drug Treatment
PubMed: 35152152
DOI: 10.1016/j.ebiom.2022.103856 -
BJR Case Reports Sep 2021We present a 1-year-old boy who presented to the emergency department with a 7-day history of diarrhoea and vomiting. The initial renal function profile demonstrated a...
We present a 1-year-old boy who presented to the emergency department with a 7-day history of diarrhoea and vomiting. The initial renal function profile demonstrated a urea of 55 mmol l (normal range between 5 and 20 mmol l), creatinine 695 micromol/L (normal range between 62-106 micromol/L) and potassium 9.1 mmol l (normal range between 3.5-5.0 mmol l), with a profound metabolic acidosis. Upon examination, there were no significant findings, specifically no neurological abnormality. He was prescribed back-to-back Salbutamol nebulisers, to increase the shift of extracellular potassium into the intracellular space, followed by i.v. calcium gluconate, with some improvement in potassium levels. A further 5 mmol of sodium bicarbonate was given, as well as a stat dose of 1 mg/kg furosemide, and per rectal calcium resonium. He was then commenced on an infusion with 10% dextrose with insulin. He was subsequently found to be in urinary retention and a catheter was inserted, which drained 1700 ml. A subsequent renal function profile, 24 hours after admission, demonstrated improvement with urea 39 mmol l, creatinine 300 micromol/L and potassium 3.0 mEq/L.
PubMed: 35136629
DOI: 10.1259/bjrcr.20210057 -
Cureus Nov 2021Introduction Increased levels of homocysteine (Hcy) may lead to endothelial damage and increase the risk of cardiovascular and renal malfunction. The current study aimed...
Introduction Increased levels of homocysteine (Hcy) may lead to endothelial damage and increase the risk of cardiovascular and renal malfunction. The current study aimed to evaluate the association of serum Hcy levels with gender, body mass index (BMI), duration of diabetes mellitus type 2 (DMT2), hemoglobin A1c (HbA1c), and blood pressure (BP). Methodology A prospective observational study was conducted at Hayatabad Medical Complex in Peshawar, Pakistan in the department of endocrinology from June 2020 to June 2021. All patients with diagnosed DMT2 above the age of 18 years were included in the study. Individuals with unconfirmed diagnoses with ages over 75 years were excluded from the study. All data including the patient's age, gender, and medical history were recorded. Height and weight were used to calculate the BMI. BP was examined thrice and a mean value was recorded for each patient. For laboratory investigation, a vial of 3 ml blood was extracted keeping sterile and aseptic conditions by a trained nurse. The sample was sent for the determination of HbA1c and serum Hcy levels. Measurement of serum Hcy was done by chemiluminescent microparticle immunoassay. All data were documented by the researchers on a predefined pro forma. Results A total of 188 patients with DMT2 were included in the study with a mean age ± SD of 54.65 ± 8.42 years. Normal (<15 micromoles per liter [mcmol/l]) serum Hcy levels were reported in 75 (39.89%) individuals, while in 47 (41.59%) individuals, there was severe (>100 mcmol/l) hyperhomocysteinemia. More than half of the patients, i.e. 157 (83.52%), had HbA1c of greater than 7%, which indicated poor glycemic control. The study revealed that the majority of the female patients, i.e. 37 (78.72%), had severe hyperhomocysteinemia (p<0.0001). Similarly, there was a direct correlation between HbA1c levels and serum Hcy. Severe hyperhomocysteinemia was found in over 80% of the patients with poor glycemic control, i.e. HbA1c >7% (p<0.0001). Furthermore, the duration of DMT2 and hypertension were both significantly associated with increased levels of Hcy with p-values of <0.0001 and <0.0001, respectively. However, no association was found between hyperhomocysteinemia and BMI. Conclusion The study revealed that increased levels of serum Hcy were associated with female gender, poor glycemic control (HbA1c >7%), BP, and duration of DMT2. However, the study failed to find an association between serum Hcy and BMI. It is recommended that patients with poor glycemic control or those with the duration of DMT2 of more than five years must be regularly checked for hyperhomocysteinemia and renal function tests. Large-scale and multi-center studies are required in order to determine the validity of these findings. The current study suggests that patients with diabetes mellitus and hypertension are likely to have increased levels of Hcy and, therefore, must be regularly screened for hyperhomocysteinemia.
PubMed: 34877198
DOI: 10.7759/cureus.19211 -
Radiology May 2022Background Data on the long-term pulmonary sequelae in COVID-19 are lacking. Purpose To assess symptoms, functional impairment, and residual pulmonary abnormalities on... (Observational Study)
Observational Study
Background Data on the long-term pulmonary sequelae in COVID-19 are lacking. Purpose To assess symptoms, functional impairment, and residual pulmonary abnormalities on serial chest CT scans in COVID-19 survivors discharged from hospital at up to 1-year follow-up. Materials and Methods Adult patients with COVID-19 discharged between March 2020 and June 2020 were prospectively evaluated at 3 months and 1 year through systematic assessment of symptoms, functional impairment, and thoracic CT scans as part of the PHENOTYPE study, an observational cohort study in COVID-19 survivors. Lung function testing was limited to participants with CT abnormalities and/or persistent breathlessness. Bonferroni correction was used. Results Eighty participants (mean age, 59 years ± 13 [SD]; 53 men) were assessed. At outpatient review, persistent breathlessness was reported in 37 of the 80 participants (46%) and cough was reported in 17 (21%). CT scans in 73 participants after discharge (median, 105 days; IQR, 95-141 days) revealed persistent abnormalities in 41 participants (56%), with ground-glass opacification (35 of 73 participants [48%]) and bands (27 of 73 participants [37%]) predominating. Unequivocal signs indicative of established fibrosis (ie, volume loss and/or traction bronchiectasis) were present in nine of 73 participants (12%). Higher admission serum C-reactive protein (in milligrams per liter), fibrinogen (in grams per deciliter), urea (millimoles per liter), and creatinine (micromoles per liter) levels; longer hospital stay (in days); older age (in years); and requirement for invasive ventilation were associated with CT abnormalities at 3-month follow-up. Thirty-two of 41 participants (78%) with abnormal findings at 3-month follow-up CT underwent repeat imaging at a median of 364 days (range, 360-366 days), with 26 (81%) showing further radiologic improvement (median, 18%; IQR, 10%-40%). Conclusion CT abnormalities were common at 3 months after COVID-19 but with signs of fibrosis in a minority. More severe acute disease was linked with CT abnormalities at 3 months. However, radiologic improvement was seen in the majority at 1-year follow-up. ClinicalTrials.gov identifier: NCT04459351. © RSNA, 2022
Topics: COVID-19; Dyspnea; Fibrosis; Hospitals; Humans; Lung; Patient Discharge; Tomography, X-Ray Computed
PubMed: 34609195
DOI: 10.1148/radiol.2021211746