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Journal of Translational Medicine Sep 2023Owing to the heterogeneity of Alzheimer's disease (AD), its pathogenic mechanisms are yet to be fully elucidated. Evidence suggests an important role of metabolism in...
BACKGROUND
Owing to the heterogeneity of Alzheimer's disease (AD), its pathogenic mechanisms are yet to be fully elucidated. Evidence suggests an important role of metabolism in the pathophysiology of AD. Herein, we identified the metabolism-related AD subtypes and feature genes.
METHODS
The AD datasets were obtained from the Gene Expression Omnibus database and the metabolism-relevant genes were downloaded from a previously published compilation. Consensus clustering was performed to identify the AD subclasses. The clinical characteristics, correlations with metabolic signatures, and immune infiltration of the AD subclasses were evaluated. Feature genes were screened using weighted correlation network analysis (WGCNA) and processed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Furthermore, three machine-learning algorithms were used to narrow down the selection of the feature genes. Finally, we identified the diagnostic value and expression of the feature genes using the AD dataset and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis.
RESULTS
Three AD subclasses were identified, namely Metabolism Correlated (MC) A (MCA), MCB, and MCC subclasses. MCA contained signatures associated with high AD progression and may represent a high-risk subclass compared with the other two subclasses. MCA exhibited a high expression of genes related to glycolysis, fructose, and galactose metabolism, whereas genes associated with the citrate cycle and pyruvate metabolism were downregulated and associated with high immune infiltration. Conversely, MCB was associated with citrate cycle genes and exhibited elevated expression of immune checkpoint genes. Using WGCNA, 101 metabolic genes were identified to exhibit the strongest association with poor AD progression. Finally, the application of machine-learning algorithms enabled us to successfully identify eight feature genes, which were employed to develop a nomogram model that could bring distinct clinical benefits for patients with AD. As indicated by the AD datasets and qRT-PCR analysis, these genes were intimately associated with AD progression.
CONCLUSION
Metabolic dysfunction is associated with AD. Hypothetical molecular subclasses of AD based on metabolic genes may provide new insights for developing individualized therapy for AD. The feature genes highly correlated with AD progression included GFAP, CYB5R3, DARS, KIAA0513, EZR, KCNC1, COLEC12, and TST.
Topics: Humans; Alzheimer Disease; Algorithms; Citrates; Citric Acid; Cluster Analysis; Shaw Potassium Channels; Nerve Tissue Proteins
PubMed: 37715200
DOI: 10.1186/s12967-023-04324-y -
Applied Microbiology and Biotechnology Dec 2024The high recurrence rate of renal uric acid stone (UAS) poses a significant challenge for urologists, and potassium sodium hydrogen citrate (PSHC) has been proven to be...
The high recurrence rate of renal uric acid stone (UAS) poses a significant challenge for urologists, and potassium sodium hydrogen citrate (PSHC) has been proven to be an effective oral dissolution drug. However, no studies have investigated the impact of PSHC on gut microbiota and its metabolites during stone dissolution therapy. We prospectively recruited 37 UAS patients and 40 healthy subjects, of which 12 patients completed a 3-month pharmacological intervention. Fasting vein blood was extracted and mid-stream urine was retained for biochemical testing. Fecal samples were collected for 16S ribosomal RNA (rRNA) gene sequencing and short chain fatty acids (SCFAs) content determination. UAS patients exhibited comorbidities such as obesity, hypertension, gout, and dyslipidemia. The richness and diversity of the gut microbiota were significantly decreased in UAS patients, Bacteroides and Fusobacterium were dominant genera while Subdoligranulum and Bifidobacterium were poorly enriched. After PSHC intervention, there was a significant reduction in stone size accompanied by decreased serum uric acid and increased urinary pH levels. The abundance of pathogenic bacterium Fusobacterium was significantly downregulated following the intervention, whereas there was an upregulation observed in SCFA-producing bacteria Lachnoclostridium and Parasutterella, leading to a significant elevation in butyric acid content. Functions related to fatty acid synthesis and amino acid metabolism within the microbiota showed upregulation following PSHC intervention. The correlation analysis revealed a positive association between stone pathogenic bacteria abundance and clinical factors for stone formation, while a negative correlation with SCFAs contents. Our preliminary study revealed that alterations in gut microbiota and metabolites were the crucial physiological adaptation to PSHC intervention. Targeted regulation of microbiota and SCFA holds promise for enhancing drug therapy efficacy and preventing stone recurrence. KEY POINTS: • Bacteroides and Fusobacterium were identified as dominant genera for UAS patients • After PSHC intervention, Fusobacterium decreased and butyric acid content increased • The microbiota increased capacity for fatty acid synthesis after PSHC intervention.
Topics: Humans; Citric Acid; Potassium Citrate; Sodium Citrate; Potassium; Uric Acid; Gastrointestinal Microbiome; Sodium; Citrates; Bacteroides; Butyric Acid
PubMed: 38183479
DOI: 10.1007/s00253-023-12953-y -
American Journal of Kidney Diseases :... Apr 2024Most previous studies of the relationship between urinary factors and kidney stone risk have either assumed a linear effect of urinary parameters on kidney stone risk or...
RATIONALE & OBJECTIVE
Most previous studies of the relationship between urinary factors and kidney stone risk have either assumed a linear effect of urinary parameters on kidney stone risk or implemented arbitrary thresholds suggesting biologically implausible "all-or-nothing" effects. In addition, little is known about the hierarchy of effects of urinary factors on kidney stone risk. This study evaluated the independent associations between urine chemistries and kidney stone formation and examined their magnitude and shape.
STUDY DESIGN
Prospective cohort study.
SETTING & PARTICIPANTS
We analyzed 9,045 24-hour urine collections from 6,217 participants of the Health Professionals Follow-Up Study and Nurses' Health Studies I and II.
EXPOSURE
Urine volume and pH, and concentrations of calcium, citrate, oxalate, potassium, magnesium, uric acid, phosphorus, and sodium.
OUTCOME
Incident symptomatic kidney stones.
ANALYTICAL APPROACH
Multivariable logistic regression analysis incorporating restricted cubic splines to explore potentially nonlinear relationships between urinary factors and the risk of forming a kidney stone. Optimal inflection point analysis was implemented for each factor, and dominance analysis was performed to establish the relative importance of each urinary factor.
RESULTS
Each urinary factor was significantly associated with stone formation except for urine pH. Higher urinary levels of calcium, oxalate, phosphorus, and sodium were associated with a higher risk of stone formation whereas higher urine volume, uric acid, citrate, potassium, and magnesium were associated with a lower risk. The relationships were substantially linear for urine calcium, uric acid, and sodium. By contrast, the magnitudes of the relationships were modestly attenuated at levels above the inflection points for urine oxalate, citrate, volume, phosphorus, potassium, and magnesium. Dominance analysis identified 3 categories of factors' relative importance: higher (calcium, volume, and citrate), intermediate (oxalate, potassium, and magnesium), and lower (uric acid, phosphorus, and sodium).
LIMITATIONS
Predominantly White participants, lack of information on stone composition.
CONCLUSIONS
Urine chemistries have complex relationships and differential relative associations with the risk of kidney stone formation.
PLAIN-LANGUAGE SUMMARY
Kidney stones are common and likely to recur. Certain urinary factors play a role in the development of stones, but their independent roles, relative importance, and shapes of association with stone formation are not well-characterized. We analyzed 24-hour urine collections from individuals with and without kidney stones. Stones were less likely in those with higher urine volume, citrate, potassium, magnesium, and uric acid and were more likely in those with higher calcium, oxalate, phosphorus, and sodium. The acidity of the urine was not related to stones. The urinary parameters showed different degrees of relative importance, with calcium, volume, and citrate being greatest. All parameters exhibited a linear or close-to-linear shape of association with stone formation.
PubMed: 38583757
DOI: 10.1053/j.ajkd.2024.02.010 -
Medicine Oct 2023Helicobacter pylori (H pylori) can cause gastritis, peptic ulcers, gastric cancer, and many other gastrointestinal diseases. The 14-day neo-dual therapy for H pylori is... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Helicobacter pylori (H pylori) can cause gastritis, peptic ulcers, gastric cancer, and many other gastrointestinal diseases. The 14-day neo-dual therapy for H pylori is considered by most countries to have good eradication rates, while the 7- and 10-day studies have been more widely explored, however, we find that their results are different. The applicability of the shorter and less expensive 10-day neo-dual therapy to our country has not yet been confirmed.
METHODS
The patients were divided into 3 groups of 200 each by randomization method. Group A: patients received vonoprazan 20 mg, bid + amoxicillin(1 g), tid, for 14 days. Group B: vonoprazan (20 mg) bid + amoxicillin (1 g) tid, duration of treatment is 10 days, group C: rabeprazole (20 mg) bid + bismuth potassium citrate tablets/tinidazole tablets/clarithromycin tablets, combined package (4.2 g), bid, duration of treatment 14 days. The main comparisons were H pylori eradication rate, adverse drug reaction profile and cost-effect ratio in each group.
RESULTS
The eradication rates of groups A, B, and C were 92.5%, 91.6%, and 80.1%, respectively. There was no significant difference in the eradication rates of groups A and B (P > .05), groups A and B had statistically significantly better eradication rates than group C (P < .05). The incidence of adverse reactions in groups A, B, and C was 9.5%, 8.5%, and 17.0%, respectively. There was no difference in the incidence of adverse reactions between A and B: (P > .05), The incidence of adverse reactions was statistically significantly lower in groups A and B than in group C (P < .05). Logistic regression analysis showed nonsmokers had a higher eradication rate (OR 2.587, 95% CI: 1.377-4.859, P = .003), and taller patients were more likely to have successful eradication (OR 1.052, 95% CI: 1.008-1.097, P = .020). Group B had the lowest cost-benefit analysis results.
CONCLUSION
Group B had an acceptable eradication rate, the lowest incidence of adverse effects, and the lowest cost analysis. Eradication is more likely to be successful in patients who do not smoke and in those who are taller.
Topics: Humans; Amoxicillin; Anti-Bacterial Agents; Clarithromycin; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Sulfonamides; Treatment Outcome
PubMed: 37832048
DOI: 10.1097/MD.0000000000035610 -
Drugs in R&D Mar 2024Potassium bismuth citrate is a gastric mucosal protector and a key drug for treating peptic ulcers.
BACKGROUND
Potassium bismuth citrate is a gastric mucosal protector and a key drug for treating peptic ulcers.
OBJECTIVE
To evaluate the pharmacokinetic characteristics and safety of 120-mg bismuth potassium citrate formulations administered orally under fasting conditions in healthy Chinese subjects.
METHOD
A single-center open two-cycle trial was conducted on 12 healthy subjects who received a single oral dose of 120 mg of bismuth potassium citrate. The plasma concentration of bismuth was determined using a validated inductively coupled plasma mass spectrometry (ICP‒MS) method. The pharmacokinetic parameters, including maximum serum concentration (C) and area under the curve concentration-time curve (AUC and AUC), and safety were evaluated via noncompartment analysis.
RESULTS
The ratios of the least square geometric mean ratio between the test (T) and reference (R) formulations for C, AUC, and AUC were 44.8%, 55.5%, and 64.4%, respectively; the bilateral 95% confidence intervals (Cis) for these parameters were 20.2-99.6%, 24.1-127.5%, and 23.7-175.0%, respectively, and the non-inferior limits for these parameters were 169.4%, 198.8%, and 200.5%, respectively. The upper limits of the one-sided 97.5% confidence interval for the least squares geometric mean ratio (T/R) were lower than the non-inferior limits. No serious adverse reactions or adverse reactions leading to detachment were observed among the subjects.
CONCLUSION
The concentration of bismuth in the blood of healthy subjects in the T formulation was not greater than that in the R formulation. Similarly, the safety of oral administration of 120 mg of bismuth potassium citrate formulations to healthy subjects was good. The trial registration number (TRN) was [2018] 013, 6 December 2018.
PubMed: 38345697
DOI: 10.1007/s40268-024-00455-9 -
BMC Urology Aug 2023To assess the routine serum and 24-hour urine tests proficiency in diagnosing the baseline metabolic abnormality of kidney stone formers.
OBJECTIVE
To assess the routine serum and 24-hour urine tests proficiency in diagnosing the baseline metabolic abnormality of kidney stone formers.
METHODS
This study analyzes the routine serum and 24-hour urine tests proficiency in diagnosing the baseline metabolic abnormality of kidney stone formers. The sensitivity and specificity, false positive, and negative results of the tests are extracted from diagnostic kits used in the laboratories of the target community. To accurately infer the results, a simulation based on 1000 people was used through 22 standard laboratory tests (Additional File 2), including calcium, oxalate, phosphate, uric acid, sulfate, potassium, sodium, citrate, and magnesium in 24-hour urine; and calcium, creatinine, Vit D, uric acid, and intact parathyroid hormone (PTH) in serum. The incremental cost-effectiveness ratio (ICER) was calculated and compared for each diagnostic test versus other diagnostic tests according to the incremental cost required for correct diagnoses of stone causes.
RESULTS
Urinary uric acid, citrate, and serum potassium constitute the cost-effectiveness boundary curve in this study. This means that other diagnostic tests are not cost-effective compared to these three tests in terms of indexing at least one item of cost and effectiveness. The ICER index for each correct diagnosis with the urinary uric acid test was $ 1.25 per diagnosis, the most cost-effective test compared to serum potassium and urinary citrate.
CONCLUSION
The simplified blood and 24-hour urine metabolic evaluation, including urinary uric acid, citrate, and serum potassium, constitute the cost-effectiveness boundary curve. The most cost-effective test was urinary uric acid measurement.
Topics: Humans; Calcium; Cost-Benefit Analysis; Uric Acid; Kidney Calculi; Citrates; Citric Acid
PubMed: 37635222
DOI: 10.1186/s12894-023-01310-w -
Alternative Therapies in Health and... Nov 2023To investigate the clinical impact of dietary intervention in combination with bismuth potassium citrate in the management of chronic atrophic gastritis (CAG) caused by... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To investigate the clinical impact of dietary intervention in combination with bismuth potassium citrate in the management of chronic atrophic gastritis (CAG) caused by Helicobacter pylori.
METHODS
From April 2019 to October 2022, 160 patients with newly identified Helicobacter pylori-related CAG were treated at our facility. They were split into two groups at random: the bismuth potassium citrate medication group (n = 80) and the diet intervention + bismuth potassium citrate experimental groups (n = 80). The bismuth potassium citrate treatment group was given bismuth potassium citrate capsule treatment only, and the diet intervention + bismuth potassium citrate treatment group was given diet intervention based on bismuth potassium citrate capsule. The diet intervention score, symptom score, and pathological score of the two groups were observed at baseline and after treatment, and the relationship between dietary intervention and symptoms and pathology of Helicobacter pylori-related CAG was analyzed.
RESULTS
During the baseline period, there was no discernible difference in the diet intervention score, symptom score, or pathology score between the two groups (P > .05); after the diet intervention combination treatment, the diet intervention score, diet intervention + bismuth potassium citrate experimental groups symptom score, and pathology score were considerably lower than those in the bismuth potassium citrate treated group (P < .05).
CONCLUSIONS
Dietary intervention combined with bismuth potassium citrate exhibited more effective treatment than bismuth potassium citrate-only treatment in Helicobacter pylori-related CAG, which hinted us proper diet has a positive impact on improving the therapeutic efficacy of bismuth potassium citrate.
Topics: Humans; Amoxicillin; Anti-Bacterial Agents; Bismuth; Drug Therapy, Combination; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Potassium; Potassium Citrate; Treatment Outcome
PubMed: 37856797
DOI: No ID Found -
Molecules (Basel, Switzerland) Sep 2023Sodium chloride (NaCl) is a commonly used additive in minimally processed fish-based products. The addition of NaCl to fish products and packaging in a modified...
Sodium chloride (NaCl) is a commonly used additive in minimally processed fish-based products. The addition of NaCl to fish products and packaging in a modified atmosphere is usually efficient with regard to limiting the occurrence of the aquatic environmental pathogen Given the negative effects of excess NaCl in the diet, there is a growing demand to reduce NaCl in food products with safer substituents, but the knowledge of their impact on antibiotic resistant is limited. This study aimed to evaluate the physiological and transcriptome characteristics of NT06 isolated from fish and to determine the effect of selected concentrations of alternative NaCl compounds (KCl/NaL/NaC) on the NT06 virulence phenotype and genotype. In the study, among the isolated microorganisms, NT06 showed the highest antibiotic resistance (to ampicillin, ceftriaxone, nalidixic acid, and norfloxacin) and the ability to grow at 4 °C. The Comprehensive Antibiotic Resistance Database (CARD) and the Virulence Factor Database (VFDB) revealed the presence of 24 and 134 gene products assigned to AMR and VF in the NT06 transcriptome, respectively. KCl, KCl/NaL and KCl/NaL/NaC inhibited pyocyanin biosynthesis, elastase activity, and protease activity from 40 to 77%. The above virulence phenotypic observations were confirmed via RT-qPCR analyses, which showed that all tested AMR and VF genes were the most downregulated due to KCl/NaL/NaC treatment. In conclusion, this study provides insight into the potential AMR and VF among foodborne and the possible impairment of those features by KCl, NaL, and NaC, which exert synergistic effects and can be used in minimally processed fish-based products.
Topics: Animals; Virulence; Anti-Bacterial Agents; Pseudomonas aeruginosa; Sodium Citrate; Sodium Lactate; Potassium Chloride; Sodium Chloride; Drug Resistance, Bacterial; Virulence Factors; Pseudomonas Infections
PubMed: 37764430
DOI: 10.3390/molecules28186654