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BMC Gastroenterology Jun 2024In Chinese healthcare settings, drug selection decisions are predominantly influenced by the Pharmacy & Therapeutics Committee (PTC). This study evaluates two recently...
BACKGROUND
In Chinese healthcare settings, drug selection decisions are predominantly influenced by the Pharmacy & Therapeutics Committee (PTC). This study evaluates two recently introduced potassium-competitive acid blockers, vonoprazan (VPZ) and tegoprazan (TPZ), utilizing the Evidence and Value: Impact on DEcisionMaking (EVIDEM) framework.
METHODS
The study employed the 10th edition of EVIDEM, which includes a core model with five domains and 13 criteria. Two independent expert panels were involved: the PTC expert panel, tasked with assigning weights using a 5-point scale, defining scoring indicators, examining the evidence matrix, scoring, and decision-making; and the evidence matrix expert panel, responsible for conducting a systematic literature review, creating the evidence matrix, and evaluating the value contributions of VPZ and TPZ.
RESULTS
The analysis estimated the value contributions of VPZ and TPZ to be 0.59 and 0.54, respectively. The domain of 'economic consequences of intervention' showed the most significant variation in value contribution between the two drugs, followed by 'comparative outcomes of intervention' and 'type of benefit of intervention'.
CONCLUSION
Employing the EVIDEM framework, VPZ's value contribution was found to be marginally superior to that of TPZ. The EVIDEM framework demonstrates potential for broader application in Chinese medical institutions.
Topics: Sulfonamides; Pyrroles; Humans; Proton Pump Inhibitors; China; Gastroesophageal Reflux; Decision Support Techniques; Cost-Benefit Analysis
PubMed: 38902604
DOI: 10.1186/s12876-024-03297-6 -
Scientific Reports Jun 2024Drought stress (DS) is a significant abiotic stress that limits agricultural productivity worldwide. In semi-arid climates, one potential solution to alleviate the...
Drought stress (DS) is a significant abiotic stress that limits agricultural productivity worldwide. In semi-arid climates, one potential solution to alleviate the deleterious effects of drought is the use of soil amendments such as nanoparticles. The current research was conducted out to probe the sway of drought at critical growth stages (CGS) of wheat crop (D: Control, D: Drought at tillering stage, and D: Drought at anthesis stage) and the application of Cu-nanoparticles (T: 0 mg L, T: 300 mg L, T: 700 mg L, and T: 950 mg L) in order to improve drought resilience. Results of the study revealed that DS considerably decreased the wheat growth and yield during CGS. However, Cu-nanoparticles application alleviated the detrimental backlash of DS and led to improvements in various aspects of wheat growth and yield, including plant height, spike length, 1000 grain weight, stomatal conductance, leaf chlorophyll content, water use efficiency, leaf turgor potential, relative water content, and ultimately the grain yield. The use of principal component analysis allowed us to integrate and interpret the diverse findings of our study, elucidating the impact of Cu-nanoparticle treatment on wheat growth and yield under drought. Overall, the study concluded that DS during the anthesis stage had the most significant negative impact on crop yield. However, applying Cu-nanoparticles at the rate of 300 mg L proved to be an effective strategy for improving crop productivity by reducing the harmful effects of drought.
Topics: Triticum; Copper; Droughts; Metal Nanoparticles; Stress, Physiological; Water; Plant Leaves; Chlorophyll; Soil
PubMed: 38902296
DOI: 10.1038/s41598-024-62680-1 -
Science Advances Jun 2024Pancreatic adenocarcinoma is the fourth leading cause of malignancy-related deaths, with rapid development of drug resistance driven by pancreatic cancer stem cells....
Pancreatic adenocarcinoma is the fourth leading cause of malignancy-related deaths, with rapid development of drug resistance driven by pancreatic cancer stem cells. However, the mechanisms sustaining stemness and chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Here, we demonstrate that Bicaudal C homolog 1 (BICC1), an RNA binding protein regulating numerous cytoplasmic mRNAs, facilitates chemoresistance and stemness in PDAC. Mechanistically, BICC1 activated tryptophan catabolism in PDAC by up-regulating indoleamine 2,3-dioxygenase-1 (IDO1) expression, a tryptophan-catabolizing enzyme. Increased levels of tryptophan metabolites contribute to NAD synthesis and oxidative phosphorylation, leading to a stem cell-like phenotype. Blocking BICC1/IDO1/tryptophan metabolism signaling greatly improves the gemcitabine (GEM) efficacy in several PDAC models with high BICC1 level. These findings indicate that BICC1 is a critical tryptophan metabolism regulator that drives the stemness and chemoresistance of PDAC and thus a potential target for combinatorial therapeutic strategy against chemoresistance.
Topics: Tryptophan; Humans; Drug Resistance, Neoplasm; Neoplastic Stem Cells; Pancreatic Neoplasms; Cell Line, Tumor; Animals; Mice; Gene Expression Regulation, Neoplastic; Carcinoma, Pancreatic Ductal; Gemcitabine; Deoxycytidine; RNA-Binding Proteins; Indoleamine-Pyrrole 2,3,-Dioxygenase
PubMed: 38896624
DOI: 10.1126/sciadv.adj8650 -
Planta Jun 2024By studying Cistus albidus shrubs in their natural habitat, we show that biological outliers can help us to understand the causes and consequences of maximum...
By studying Cistus albidus shrubs in their natural habitat, we show that biological outliers can help us to understand the causes and consequences of maximum photochemical efficiency decreases in plants, thus reinforcing the importance of integrating these often-neglected data into scientific practice. Outliers are individuals with exceptional traits that are often excluded of data analysis. However, this may result in very important mistakes not accurately capturing the true trajectory of the population, thereby limiting our understanding of a given biological process. Here, we studied the role of biological outliers in understanding the causes and consequences of maximum photochemical efficiency decreases in plants, using the semi-deciduous shrub C. albidus growing in a Mediterranean-type ecosystem. We assessed interindividual variability in winter, spring and summer maximum PSII photochemical efficiency in a population of C. albidus growing under Mediterranean conditions. A strong correlation was observed between maximum PSII photochemical efficiency (F/F ratio) and leaf water desiccation. While decreases in maximum PSII photochemical efficiency did not result in any damage at the organ level during winter, reductions in the F/F ratio were associated to leaf mortality during summer. However, all plants could recover after rainfalls, thus maximum PSII photochemical efficiency decreases did not result in an increased mortality at the organism level, despite extreme water deficit and temperatures exceeding 40ºC during the summer. We conclude that, once methodological outliers are excluded, not only biological outliers must not be excluded from data analysis, but focusing on them is crucial to understand the causes and consequences of maximum PSII photochemical efficiency decreases in plants.
Topics: Photosystem II Protein Complex; Seasons; Plant Leaves; Cistus; Photosynthesis; Ecosystem; Water; Temperature; Chlorophyll
PubMed: 38896307
DOI: 10.1007/s00425-024-04466-3 -
Clinical Cardiology Jun 2024Statins are lipid-lowering drugs with favorable anti-inflammatory effects. This study aimed to explore different statin-based lipid-lowering strategies to reduce... (Comparative Study)
Comparative Study
BACKGROUND
Statins are lipid-lowering drugs with favorable anti-inflammatory effects. This study aimed to explore different statin-based lipid-lowering strategies to reduce high-sensitivity C-reactive protein (hs-CRP).
HYPOTHESIS
The hypothesis is that different statin-based lipid-lowering strategies might reduce hs-CRP.
METHODS
This retrospective study included 3653 patients who underwent percutaneous coronary intervention (PCI). Three statin-based lipid-lowering strategies were investigated, including different types of statins (atorvastatin vs. rosuvastatin), statin combined with ezetimibe therapy (vs. without), and intensive statin therapy (vs. regular). The hs-CRP levels and blood lipid indicators were measured at baseline and after 1-month lipid-lowering therapy. Multivariable linear regression analysis and structural equation mode analysis were conducted to verify the association between different lipid-lowering strategies, Δhs-CRP (%) and ΔLDL-C (%).
RESULTS
Totally, 3653 patients were enrolled with an average age of 63.81 years. Multivariable linear regression demonstrated that statin combined with ezetimibe therapy was significantly associated with decreased Δhs-CRP (%) (β = -0.253, 95% CI: [-0.501 to -0.005], p = 0.045). The increased ΔLDL-C (%) was an independent predictor of elevated levels of Δhs-CRP (%) (β = 0.487, 95% CI: [0.15-0.824], p = 0.005). Furthermore, structural equation model analysis proved that statin combined with ezetimibe therapy (β = -0.300, p < 0.001) and intensive statin therapy (β = -0.032, p = 0.043) had an indirect negative effect on Δhs-CRP via ΔLDL-C.
CONCLUSIONS
Compared with routine statin use, statin combined with ezetimibe therapy and intensive statin therapy could further reduce hs-CRP levels.
Topics: Humans; Male; Retrospective Studies; Female; Hydroxymethylglutaryl-CoA Reductase Inhibitors; C-Reactive Protein; Coronary Artery Disease; Middle Aged; Biomarkers; Treatment Outcome; Percutaneous Coronary Intervention; Ezetimibe; Drug Therapy, Combination; Aged; Rosuvastatin Calcium; Atorvastatin; Cholesterol, LDL; Anticholesteremic Agents; Dyslipidemias
PubMed: 38895772
DOI: 10.1002/clc.24301 -
Molecules (Basel, Switzerland) May 2024Cytochrome P450s (P450s), a superfamily of heme-containing enzymes, existed in animals, plants, and microorganisms. P450s can catalyze various regional and... (Review)
Review
Cytochrome P450s (P450s), a superfamily of heme-containing enzymes, existed in animals, plants, and microorganisms. P450s can catalyze various regional and stereoselective oxidation reactions, which are widely used in natural product biosynthesis, drug metabolism, and biotechnology. In a typical catalytic cycle, P450s use redox proteins or domains to mediate electron transfer from NAD(P)H to heme iron. Therefore, the main factors determining the catalytic efficiency of P450s include not only the P450s themselves but also their redox-partners and electron transfer pathways. In this review, the electron transfer pathway engineering strategies of the P450s catalytic system are reviewed from four aspects: cofactor regeneration, selection of redox-partners, P450s and redox-partner engineering, and electrochemically or photochemically driven electron transfer.
Topics: Cytochrome P-450 Enzyme System; Electron Transport; Protein Engineering; Oxidation-Reduction; Heme; Animals; Humans
PubMed: 38893355
DOI: 10.3390/molecules29112480 -
Nutrients Jun 2024, commonly known as , is a photosynthetic filamentous cyanobacterium (blue-green microalga) that has been utilized as a food source since ancient times. More recently,... (Review)
Review
, commonly known as , is a photosynthetic filamentous cyanobacterium (blue-green microalga) that has been utilized as a food source since ancient times. More recently, it has gained significant popularity as a dietary supplement due to its rich content of micro- and macro-nutrients. Of particular interest is a water soluble phycobiliprotein derived from known as phycocyanin C (C-PC), which stands out as the most abundant protein in this cyanobacterium. C-PC is a fluorescent protein, with its chromophore represented by the tetrapyrrole molecule phycocyanobilin B (PCB-B). While C-PC is commonly employed in food for its coloring properties, it also serves as the molecular basis for numerous nutraceutical features associated with . Indeed, the comprehensive C-PC, and to some extent, the isolated PCB-B, has been linked to various health-promoting effects. These benefits encompass conditions triggered by oxidative stress, inflammation, and other pathological conditions. The present review focuses on the bio-pharmacological properties of these molecules, positioning them as promising agents for potential new applications in the expanding nutraceutical market.
Topics: Dietary Supplements; Spirulina; Phycocyanin; Humans; Phycobilins; Phycobiliproteins; Oxidative Stress
PubMed: 38892686
DOI: 10.3390/nu16111752 -
Nutrients May 2024The prevalence of anaemia in India remains high in children, especially those in rural areas, and in women of childbearing age, and its impairment of neurological... (Review)
Review
The prevalence of anaemia in India remains high in children, especially those in rural areas, and in women of childbearing age, and its impairment of neurological development can have serious lifelong effects. It is concerning that the most recent official data (2019-21) indicate an increased prevalence compared with 2015-16. There is also considerable variability in childhood anaemia between Indian states with socioeconomic factors, such as wealth and education contributing to the risk of anaemia among adolescent women and their children. Dietary iron deficiency is often regarded as the main contributor to anaemia but increasing evidence accumulated from the authors' ongoing literature database coupled with recent literature research suggests that it has a multifactorial aetiology, some of which is not related to nutrition. This narrative review focused on these multifactorial issues, notably the contribution of vitamin B/folate deficiency, which also has a high prevalence in India. It was also noted that the dietary intake of bioavailable iron remains an important contributor for reducing anaemia, and the role of millets as an improved iron source compared to traditional staple cereals is briefly discussed. The overall conclusion is that anaemia has a multifactorial aetiology requiring multifactorial assessment that must include assessment of vitamin B status.
Topics: Humans; India; Prevalence; Vitamin B 12 Deficiency; Female; Anemia; Folic Acid Deficiency; Adolescent; Child; Anemia, Iron-Deficiency; Male; Iron, Dietary; Nutritional Status; Adult; Risk Factors; Diet; Vitamin B 12
PubMed: 38892606
DOI: 10.3390/nu16111673 -
Nutrients May 2024Exploring the link between genetic polymorphisms in folate metabolism genes (MTHFR, MTR, and MTRR) and cardiovascular disease (CVD), this study evaluates the effect of B... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of Methylfolate, Pyridoxal-5'-Phosphate, and Methylcobalamin (Soloways) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized...
Exploring the link between genetic polymorphisms in folate metabolism genes (MTHFR, MTR, and MTRR) and cardiovascular disease (CVD), this study evaluates the effect of B vitamin supplements (methylfolate, pyridoxal-5'-phosphate, and methylcobalamin) on homocysteine and lipid levels, potentially guiding personalized CVD risk management. In a randomized, double-blind, placebo-controlled trial, 54 patients aged 40-75 with elevated homocysteine and moderate LDL-C levels were divided based on MTHFR, MTR, and MTRR genetic polymorphisms. Over six months, they received either a combination of methylfolate, P5P, and methylcobalamin, or a placebo. At the 6 months follow-up, the treatment group demonstrated a significant reduction in homocysteine levels by 30.0% (95% CI: -39.7% to -20.3%) and LDL-C by 7.5% (95% CI: -10.3% to -4.7%), compared to the placebo ( < 0.01 for all). In the subgroup analysis, Homozygous Minor Allele Carriers showed a more significant reduction in homocysteine levels (48.3%, 95% CI: -62.3% to -34.3%, < 0.01) compared to mixed allele carriers (18.6%, 95% CI: -25.6% to -11.6%, < 0.01), with a notable intergroup difference (29.7%, 95% CI: -50.7% to -8.7%, < 0.01). LDL-C levels decreased by 11.8% in homozygous carriers (95% CI: -15.8% to -7.8%, < 0.01) and 4.8% in mixed allele carriers (95% CI: -6.8% to -2.8%, < 0.01), with a significant between-group difference (7.0%, 95% CI: -13.0% to -1.0%, < 0.01). Methylfolate, P5P, and methylcobalamin supplementation tailored to genetic profiles effectively reduced homocysteine and LDL-C levels in patients with specific MTHFR, MTR, and MTRR polymorphisms, particularly with homozygous minor allele polymorphisms.
Topics: Humans; Middle Aged; Homocysteine; Female; Male; Dietary Supplements; Methylenetetrahydrofolate Reductase (NADPH2); Double-Blind Method; 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Cholesterol, LDL; Aged; Vitamin B 12; Pyridoxal Phosphate; Adult; Ferredoxin-NADP Reductase; Tetrahydrofolates; Polymorphism, Genetic; Vitamin B Complex
PubMed: 38892484
DOI: 10.3390/nu16111550 -
International Journal of Molecular... May 2024Anoctamin1 (ANO1), a calcium-activated chloride channel, is overexpressed in a variety of cancer cells, including prostate cancer, and is involved in cancer cell...
Anoctamin1 (ANO1), a calcium-activated chloride channel, is overexpressed in a variety of cancer cells, including prostate cancer, and is involved in cancer cell proliferation, migration, and invasion. Inhibition of ANO1 in these cancer cells exhibits anticancer effects. In this study, we conducted a screening to identify novel ANO1 inhibitors with anticancer effects using PC-3 human prostate carcinoma cells. Screening of 2978 approved and investigational drugs revealed that hemin is a novel ANO1 inhibitor with an IC value of 0.45 μM. Notably, hemin had no significant effect on intracellular calcium signaling and cystic fibrosis transmembrane conductance regulator (CFTR), a cyclic AMP (cAMP)-regulated chloride channel, and it showed a weak inhibitory effect on ANO2 at 3 μM, a concentration that completely inhibits ANO1. Interestingly, hemin also significantly decreased ANO1 protein levels and strongly inhibited the cell proliferation and migration of PC-3 cells in an ANO1-dependent manner. Furthermore, it strongly induced caspase-3 activation, PARP degradation, and apoptosis in PC-3 cells. These findings suggest that hemin possesses anticancer properties via ANO1 inhibition and could be considered for development as a novel treatment for prostate cancer.
Topics: Humans; Anoctamin-1; Male; Hemin; Prostatic Neoplasms; Cell Proliferation; Neoplasm Proteins; Cell Movement; Apoptosis; Antineoplastic Agents; Cell Line, Tumor; PC-3 Cells
PubMed: 38892219
DOI: 10.3390/ijms25116032