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Asian Pacific Journal of Cancer... Jun 2024The 2x2 factorial design is an effective method that allows for multiple comparisons, especially in the context of interactions between different interventions, without... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The 2x2 factorial design is an effective method that allows for multiple comparisons, especially in the context of interactions between different interventions, without substantially increasing the required sample size. In view of the considerable preclinical evidence for Curcumin and Metformin in preventing the development and progression of head and neck squamous cell carcinoma (HNSCC), this study describes the protocol of the clinical trial towards applying the drug combination in prevention of second primary tumors.
METHODS
We have applied the trial design to a large phase IIB/III double-blind, multi-centric, placebo-controlled, randomized clinical trial to determine the safety and efficacy of Metformin and Curcumin in the prevention of second primary tumours (SPT) of the aerodigestive tract following treatment of HNSCC (n=1,500) [Clinical Registry of India, CTRI/2018/03/012274]. Patients recruited in this trial will receive Metformin (with placebo), Curcumin (with placebo), Metformin, and Curcumin or placebo alone for a period of 36 months. The primary endpoint of this trial is the development of SPT, while the secondary endpoints are toxicities associated with the agents, incidence of recurrence, and identifying potential biomarkers. In this article, we discuss the 2x2 factorial design and how it applies to the head and neck cancer chemoprevention trial.
CONCLUSION
2x2 factorial design is an effective trial design for chemoprevention clinical trials where the effectiveness of multiple interventions needs to be tested parallelly.
Topics: Humans; Metformin; Curcumin; Head and Neck Neoplasms; Double-Blind Method; Neoplasms, Second Primary; Male; Female; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Combined Chemotherapy Protocols; Middle Aged; Adult; Follow-Up Studies; Prognosis; Research Design; Aged; Randomized Controlled Trials as Topic
PubMed: 38918654
DOI: 10.31557/APJCP.2024.25.6.1935 -
Journal of Health, Population, and... Jun 2024Even after the peak of the COVID-19 pandemic, the number of mild cases remains high, requiring continuous control. Curcumin, owing to its anti-inflammatory properties,... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Even after the peak of the COVID-19 pandemic, the number of mild cases remains high, requiring continuous control. Curcumin, owing to its anti-inflammatory properties, can suppress vital proliferation and cytokine secretion in animal models. We developed a highly absorbable curcumin, curcuRouge (cR), which is approximately 100 times more orally bioavailable than conventional curcumin. We evaluated the effect of cR on the inhibition of disease progression in asymptomatic or mildly symptomatic COVID-19 patients.
METHODS
This study evaluated the effect of 7-day oral intake of cR (360 mg twice daily). Patients within 5 days of COVID-19 diagnosis were randomly assigned to a placebo or cR group in a double-blind manner.
RESULTS
Primary endpoint events [body temperature (BT) ≥ 37.5 °C and saturation of percutaneous oxygen (SpO2) < 96%] were fewer than expected, and the rate of these events was 2.8% in the cR group (2/71) and 6.0% in the placebo group (4/67); hazard ratio (HR) = 0.532, 95% confidence interval (CI) 0.097-2.902. Patients receiving cR tended to take fewer antipyretic medications than those receiving placebo (HR = 0.716, 95% CI 0.374-1.372). Among patients with a normal range of BT at baseline, the BT change rate was significantly (p = 0.014) lower in the cR group (- 0.34%) versus placebo (- 0.01%).
CONCLUSION
The relative suppression of event rates and antipyretic medications taken, and significant decrease of subclinical BT support the anti-inflammatory effects of cR in asymptomatic or mildly symptomatic patients with COVID-19.
TRIAL REGISTRATION
Japan Registry of Clinical Trials (CRB5200002).
Topics: Humans; Curcumin; Double-Blind Method; Male; Female; Middle Aged; COVID-19 Drug Treatment; Administration, Oral; Adult; COVID-19; Aged; Treatment Outcome; SARS-CoV-2; Biological Availability
PubMed: 38915116
DOI: 10.1186/s41043-024-00584-6 -
PloS One 2024The intricate process of neuronal differentiation integrates multiple signals to induce transcriptional, morphological, and electrophysiological changes that reshape the...
The intricate process of neuronal differentiation integrates multiple signals to induce transcriptional, morphological, and electrophysiological changes that reshape the properties of neural precursor cells during their maturation and migration process. An increasing number of neurotransmitters and biomolecules have been identified as molecular signals that trigger and guide this process. In this sense, taurine, a sulfur-containing, non-essential amino acid widely expressed in the mammal brain, modulates the neuronal differentiation process. In this study, we describe the effect of taurine acting via the ionotropic GABAA receptor and the metabotropic GABAB receptor on the neuronal differentiation and electrophysiological properties of precursor cells derived from the subventricular zone of the mouse brain. Taurine stimulates the number of neurites and favors the dendritic complexity of the neural precursor cells, accompanied by changes in the somatic input resistance and the strength of inward and outward membranal currents. At the pharmacological level, the blockade of GABAA receptors inhibits these effects, whereas the stimulation of GABAB receptors has no positive effects on the taurine-mediated differentiation process. Strikingly, the blockade of the GABAB receptor with CGP533737 stimulates neurite outgrowth, dendritic complexity, and membranal current kinetics of neural precursor cells. The effects of taurine on the differentiation process involve Ca2+ mobilization and the activation of intracellular signaling cascades since chelation of intracellular calcium with BAPTA-AM, and inhibition of the CaMKII, ERK1/2, and Src kinase inhibits the neurite outgrowth of neural precursor cells of the subventricular zone.
Topics: Animals; Neural Stem Cells; Receptors, GABA-B; Mice; Cell Differentiation; Receptors, GABA-A; Lateral Ventricles; Taurine; Neurogenesis; Calcium
PubMed: 38913632
DOI: 10.1371/journal.pone.0305853 -
PloS One 2024Gaseous and semi-volatile organic compounds emitted by the transport sector contribute to air pollution and have adverse effects on human health. To reduce harmful...
Gaseous and semi-volatile organic compounds emitted by the transport sector contribute to air pollution and have adverse effects on human health. To reduce harmful effects to the environment as well as to humans, renewable and sustainable bio-hybrid fuels are explored and investigated in the cluster of excellence "The Fuel Science Center" at RWTH Aachen University. However, data on the effects of bio-hybrid fuels on human health is scarce, leaving a data gap regarding their hazard potential. To help close this data gap, this study investigates potential toxic effects of a Ketone-Ester-Alcohol-Alkane (KEAA) fuel blend on A549 human lung cells. Experiments were performed using a commercially available air-liquid interface exposure system which was optimized beforehand. Then, cells were exposed at the air-liquid interface to 50-2000 ppm C3.7 of gaseous KEAA for 1 h. After a 24 h recovery period in the incubator, cells treated with 500 ppm C3.7 KEAA showed significant lower metabolic activity and cells treated with 50, 250, 500 and 1000 ppm C3.7 KEAA showed significant higher cytotoxicity compared to controls. Our data support the international occupational exposure limits of the single KEAA constituents. This finding applies only to the exposure scenario tested in this study and is difficult to extrapolate to the complex in vivo situation.
Topics: Humans; A549 Cells; Lung; Biofuels; Cell Survival; Gases; Volatile Organic Compounds; Alkanes; Air Pollutants
PubMed: 38913629
DOI: 10.1371/journal.pone.0300772 -
Scientific Reports Jun 2024The objective of this study was to investigate the effect of microencapsulated bioactive compounds from lemongrass mixed dragon fruit peel pellet (MiEn-LEDRAGON)...
The objective of this study was to investigate the effect of microencapsulated bioactive compounds from lemongrass mixed dragon fruit peel pellet (MiEn-LEDRAGON) supplementation on fermentation characteristics, nutrient degradability, methane production, and the microbial diversity using in vitro gas production technique. The study was carried out using a completely randomized design (CRD) with five levels of MiEn-LEDRAGON supplementation at 0, 1, 2, 3, and 4% of the total dry matter (DM) substrate. Supplementation of MiEn-LEDRAGON in the diet at levels of 3 or 4% DM resulted in increased (p < 0.05) cumulative gas production at 96 hours (h) of incubation time, reaching up to 84.842 ml/ 0.5 g DM. Furthermore, supplementation with 3% MiEn-LEDRAGON resulted in higher in vitro nutrient degradability and ammonia-nitrogen concentration at 24 h of the incubation time when compared to the control group (without supplementation) by 5.401% and 11.268%, respectively (p < 0.05). Additionally, supplementation with MiEn-LEDRAGON in the diet led to an increase in the population of Fibrobacter succinogenes at 24 h and Butyrivibrio fibrisolvens at 12 h, while decreasing the population of Ruminococcus albus, Ruminococcus flavefaciens, and Methanobacteriales (p < 0.05). Moreover, supplementation of MiEn-LEDRAGON in the diet at levels of 2 to 4% DM resulted in a higher total volatile fatty acids (VFA) at 24 h, reaching up to 73.021 mmol/L (p < 0.05). Additionally, there was an increased proportion of propionic acid (C3) and butyric acid (C4) at 12 h (p < 0.05). Simultaneously, there was a decrease in the proportion of acetic acid (C2) and the ratio of acetic acid to propionic acid (C2:C3), along with a reduction of methane (CH) production by 11.694% when comparing to the 0% and 3% MiEn-LEDRAGON supplementation (p < 0.05). In conclusion, this study suggests that supplementing MiEn-LEDRAGON at 3% of total DM substrate could be used as a feed additive rich in phytonutrients for ruminants.
Topics: Rumen; Fermentation; Animals; Gastrointestinal Microbiome; Dietary Supplements; Methane; Animal Feed; Phytochemicals; Fatty Acids, Volatile
PubMed: 38910145
DOI: 10.1038/s41598-024-59697-x -
Scientific Reports Jun 2024Breast cancer (BC) remains a significant health concern for women globally, prompting the relentless pursuit of novel therapeutic modalities. As a traditional Chinese...
Breast cancer (BC) remains a significant health concern for women globally, prompting the relentless pursuit of novel therapeutic modalities. As a traditional Chinese medicine, Boswellia carterii has been extensively used to treat various cancers, such as BC. However, the anti-BC effect and underlying mechanism of Boswellia carterii remain largely unclear. The aim of this study is to explore the therapeutic effect of Boswellia carterii n-hexane extract (BCHE) against BC as well as its underlying mechanism. The present study showed that BCHE significantly suppressed the viability of human BC cells. Moreover, BCHE exhibited potent anti-BC activity in vivo with no significant toxic effects. Additionally, BCHE induced ferroptosis via increased Transferrin expression and the intracellular accumulation of Fe, as well as decreased glutathione peroxidase 4 (GPX4) expression and the upregulation of reactive oxygen species (ROS)-induced lipid peroxidation in BC cells. In vivo experimental results also demonstrated that BCHE effectively induced ferroptosis through GPX4 downregulation and Transferrin upregulation in tumor-bearing mice. Overall, BCHE inhibited the growth of BC cells by inducing ferroptosis mediated by modulating the iron accumulation pathway and the lipid peroxidation pathway. Therefore, BCHE could serve as a potential ferroptosis-targeting drug for treating BC.
Topics: Ferroptosis; Phospholipid Hydroperoxide Glutathione Peroxidase; Humans; Breast Neoplasms; Female; Animals; Transferrin; Mice; Plant Extracts; Cell Line, Tumor; Boswellia; Reactive Oxygen Species; Xenograft Model Antitumor Assays; Cell Proliferation; Hexanes; Down-Regulation; Lipid Peroxidation; Up-Regulation; Gene Expression Regulation, Neoplastic; Mice, Nude; Mice, Inbred BALB C
PubMed: 38906931
DOI: 10.1038/s41598-024-65170-6 -
Nature Communications Jun 2024Lacustrine methane emissions are strongly mitigated by aerobic methane-oxidizing bacteria (MOB) that are typically most active at the oxic-anoxic interface. Although...
Lacustrine methane emissions are strongly mitigated by aerobic methane-oxidizing bacteria (MOB) that are typically most active at the oxic-anoxic interface. Although oxygen is required by the MOB for the first step of methane oxidation, their occurrence in anoxic lake waters has raised the possibility that they are capable of oxidizing methane further anaerobically. Here, we investigate the activity and growth of MOB in Lake Zug, a permanently stratified freshwater lake. The rates of anaerobic methane oxidation in the anoxic hypolimnion reached up to 0.2 µM d. Single-cell nanoSIMS measurements, together with metagenomic and metatranscriptomic analyses, linked the measured rates to MOB of the order Methylococcales. Interestingly, their methane assimilation activity was similar under hypoxic and anoxic conditions. Our data suggest that these MOB use fermentation-based methanotrophy as well as denitrification under anoxic conditions, thus offering an explanation for their widespread presence in anoxic habitats such as stratified water columns. Thus, the methane sink capacity of anoxic basins may have been underestimated by not accounting for the anaerobic MOB activity.
Topics: Methane; Lakes; Oxidation-Reduction; Anaerobiosis; Methylococcaceae; Metagenomics; Oxygen
PubMed: 38906896
DOI: 10.1038/s41467-024-49602-5 -
Ecotoxicology and Environmental Safety Jun 2024Copper (Cu) is a necessary mineral nutrient for plant growth and development and is involved in several morphological, physiological, and biochemical processes; however,...
Integrated physiological, biochemical, and transcriptomic analyses of Bruguiera gymnorhiza leaves under long-term copper stress: Stomatal size, wax crystals and composition.
Copper (Cu) is a necessary mineral nutrient for plant growth and development and is involved in several morphological, physiological, and biochemical processes; however, high concentrations of Cu can negatively impact these processes. The role of stomata in responding to various biotic and abiotic stimuli has not been studied in Bruguiera gymnorhiza, particularly in terms of their coordinated interactions at the molecular, physiological, and biochemical levels. Moreover, numerous plants employ strategies such as the presence of thick waxy cuticles on their leaf epidermis and the closing of stomata to reduce water loss. Thus, this study investigates the accumulation of Cu in B. gymnorhiza and its effect on leaf morphology and the molecular response under different Cu treatments (0, 200, and 400 mg L⁻¹, Cu0, Cu200, and Cu400, respectively) during a two years stress period. The results show that Cu stress affected accumulation and transport, increased the activities of peroxidase and ascorbate peroxidase, concentrations of soluble sugar, proline, and HO, and decreased the activity of catalase and content of malondialdehyde. Also, Cu-induced stress decreased the uptake of phosphorus and nitrogen and inhibited plant photosynthesis, which consequently led to reduced plant growth. Scanning electron microscopy combined with gas chromatography-mass spectrometry showed that B. gymnorhiza leaves had higher wax crystals and compositions under increased Cu stress, which forced the leaf's stomata to be closed. Also, the contents of alkanes, alcohols, primary alcohol levels (C26:0, C28:0, C30:0, and C32:0), n-Alkanes (C29 and C30), and other wax loads were significantly higher, while fatty acid (C12, C16, and C18) was lower in Cu200 and Cu400 compared to Cu0. Furthermore, the transcriptomic analyses revealed 1240 (771 up- and 469 downregulated), 1000 (723 up- and 277 down-regulated), and 1476 (808 up- and 668 downregulated) differentially expressed genes in Cu0 vs Cu200, Cu0 vs Cu400, and Cu200 vs Cu400, respectively. RNA-seq analyses showed that Cu mainly affected eight pathways, including photosynthesis, cutin, suberin, and wax biosynthesis. This study provides a reference for understanding mangrove response to heavy metal stress and developing novel management practices.
PubMed: 38905937
DOI: 10.1016/j.ecoenv.2024.116609 -
Journal of Chromatography. A Jun 2024A system consisting of a thermal desorption unit (TDU) and micro thermal desorption tubes (μTD-tubes, 1.4 mm I.D., 10mg Tenax TA) for fast desorption of analytes was...
A system consisting of a thermal desorption unit (TDU) and micro thermal desorption tubes (μTD-tubes, 1.4 mm I.D., 10mg Tenax TA) for fast desorption of analytes was developed for the efficient combination of hyper fast gas chromatography with thermal desorption. The fast desorption is achieved by a significantly reduced thermal mass compared to conventional thermal desorption tubes. Therefore, extremely fast heating and cooling cycles are possible. Proof of concept measurements combining the new setup with a flow-field thermal gradient gas chromatograph (FF-TG-GC) and FID detection show good precision and linearity with R≥0.995 in the analysis of an n-alkane mix (C-C). Thermal desorption occurs within 12s. The impact of reduced μTD-tube dimensions on desorption time, full width at half maximum (FWHM), breakthrough volumes, tube flow rates ergo linear velocities, porosity and back pressure is discussed.
PubMed: 38901296
DOI: 10.1016/j.chroma.2024.465039 -
Nature Communications Jun 2024Sulfur-containing scaffolds originating from small alkyl fragments play a crucial role in various pharmaceuticals, agrochemicals, and materials. Nonetheless, their...
Sulfur-containing scaffolds originating from small alkyl fragments play a crucial role in various pharmaceuticals, agrochemicals, and materials. Nonetheless, their synthesis using conventional methods presents significant challenges. In this study, we introduce a practical and efficient approach that harnesses hydrogen atom transfer photocatalysis to activate volatile alkanes, such as isobutane, butane, propane, ethane, and methane. Subsequently, these nucleophilic radicals react with SO to yield the corresponding sulfinates. These sulfinates then serve as versatile building blocks for the synthesis of diverse sulfur-containing organic compounds, including sulfones, sulfonamides, and sulfonate esters. Our use of flow technology offers a robust, safe and scalable platform for effectively activating these challenging gaseous alkanes, facilitating their transformation into valuable sulfinates.
PubMed: 38897988
DOI: 10.1038/s41467-024-49322-w