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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 -
PloS One 2024Post-induction hypotension (PIH) often occurs during general anesthesia induction. This study aimed to investigate blood catecholamine levels during induction of general...
Changes in blood catecholamines during induction of general anesthesia in patients with post-induction hypotension undergoing laparoscopic cholecystectomy: A single-center prospective cohort study.
BACKGROUND
Post-induction hypotension (PIH) often occurs during general anesthesia induction. This study aimed to investigate blood catecholamine levels during induction of general anesthesia in patients with PIH undergoing laparoscopic cholecystectomy.
METHODS
This prospective study included 557 adult patients who underwent laparoscopic cholecystectomy under general anesthesia. PIH was defined as a greater than 20% decrease in systolic blood pressure from the pre-induction value, a systolic arterial pressure of less than 90 mmHg, or both. Plasma concentrations of epinephrine and norepinephrine during the induction of general anesthesia were determined using enzyme-linked immunosorbent assay. Multivariate logistic regression analysis evaluated the association between the clinical factors and PIH.
RESULTS
Of the 557 patients, 390 had PIH, and the remaining 167 were allocated to the non-PIH group. Changes in blood adrenaline, noradrenaline levels, or both were more pronounced in the PIH than in the non-PIH group (p<0.05). Age, body mass index, a history of hypertension, preoperative systolic blood pressure, and propofol or sufentanil dose were independent predictors of PIH.
CONCLUSION
The changes of blood catecholamines in patients with more stable hemodynamics during the induction of general anesthesia are smaller than that in patients with post-induction hypotension.
TRIAL REGISTRATION
ChiCTR2200055549, 12/01/2022.
Topics: Humans; Cholecystectomy, Laparoscopic; Male; Female; Anesthesia, General; Middle Aged; Prospective Studies; Hypotension; Adult; Catecholamines; Blood Pressure; Aged; Norepinephrine; Epinephrine
PubMed: 38917102
DOI: 10.1371/journal.pone.0305980 -
Microbiology Spectrum Jun 2024Physicochemical methods for remediating phenol-contaminated soils are costly and inefficient, making biodegradation an environmentally friendly alternative approach....
Physicochemical methods for remediating phenol-contaminated soils are costly and inefficient, making biodegradation an environmentally friendly alternative approach. This study aims to screen for potential phenol-degrading bacteria and to verify the removal capacities of a selected strain in a bioaugmentation experiment at the greenhouse level using L. (Chinese cabbage) as the model plant and phenol-contaminated soil. In parallel, pot experiments were conducted using a collaborative approach based on this model system. We found that strain H13 showed a high degradation capability, with a 97.67% efficiency in degrading 100 mg/L phenol. Under shaking flask conditions, H13 facilitated the solubilization of tricalcium phosphate and potassium feldspar powder. Pot experiments suggested a phenol removal percentage of 89.22% and enhanced availability of soil phosphorus and potassium for plants with H13 inoculation. In this case, the abundance of soil microbes and the activity of soil enzymes significantly increased as well. Furthermore, both photosynthesis and the antioxidant system in Chinese cabbage were enhanced following H13 inoculation, resulting in its increased yield and quality. Partial least squares path modeling revealed that H13 can primarily affect plant root growth, with a secondary impact on photosynthesis. These findings highlight the potential of biodegradation from phenol-degrading bacteria as a promising strategy for efficient phenol removal from soil while promoting plant growth and health.IMPORTANCEThis study is significant for environmental remediation and agriculture by its exploration of a more environmentally friendly and cost-effective bio-strategy in treating phenol-contaminated soil. These findings have essential implications for environmental remediation efforts and sustainable agriculture. By utilizing the biodegradation capabilities of strain H13, it is possible to remove phenol contaminants from the soil efficiently, reducing their negative effects. Furthermore, the enhanced growth and health of the Chinese cabbage plants indicate the potential of this approach to promote sustainable crop production.
PubMed: 38916316
DOI: 10.1128/spectrum.00266-24 -
BioRxiv : the Preprint Server For... Jun 2024Cdk5 is a highly-conserved, noncanonical cell division kinase important to the terminal differentiation of mammalian cells in multiple organ systems. We previously...
Cdk5 is a highly-conserved, noncanonical cell division kinase important to the terminal differentiation of mammalian cells in multiple organ systems. We previously identified Pef1, the ortholog of cdk5, as regulator of chronological lifespan. To reveal the processes impacted by Pef1, we developed APEX2-biotin phenol-mediated proximity labeling in Efficient labeling required a short period of cell wall digestion and eliminating glucose and nitrogen sources from the medium. We identified 255 high-confidence Pef1 neighbors in growing cells and a novel Pef1-interacting partner, the DNA damage response protein Rad24. The Pef1-Rad24 interaction was validated by reciprocal proximity labeling and co-immunoprecipitation. Eliminating Pef1 partially rescued the DNA damage sensitivity of cells lacking Rad24. To monitor how Pef1 neighbors change under different conditions, cells induced for autophagy were labeled and 177 high-confidence Pef1 neighbors were identified. Gene ontology (GO) analysis of the Pef1 neighbors identified proteins participating in processes required for autophagosome expansion including regulation of actin dynamics and vesicle-mediated transport. Some of these proteins were identified in both exponentially growing and autophagic cells. Pef1-APEX2 proximity labeling therefore identified a new Pef1 function in modulating the DNA damage response and candidate processes that Pef1 and other cdk5 orthologs may regulate.
PubMed: 38915521
DOI: 10.1101/2024.06.12.598664 -
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 -
Scientific Reports Jun 2024Rose flowers (Rosa hybrida L.) are highly perishable and have a limited vase life. This study evaluated the effects of preharvest foliar applications of γ-aminobutyric...
Rose flowers (Rosa hybrida L.) are highly perishable and have a limited vase life. This study evaluated the effects of preharvest foliar applications of γ-aminobutyric acid (GABA) and calcium chloride (CaCl), individually and combined, on antioxidant responses and vase life of cut Jumilia rose flowers. Treatments included foliar sprays of GABA at 0, 20, 40, and 60 mM and CaCl at 0, 0.75%, and 1.5%, applied in a factorial design within a completely randomized setup before harvest. Results showed GABA and CaCl interaction (especially, 60 mM GABA and 1.5% CaCl) significantly increased enzymatic antioxidants including superoxide dismutase, catalase, and peroxidase, as well as non-enzymatic antioxidants such as flavonoids, carotenoids, phenolics, and antioxidant activity in petals compared to control. SOD activity in roses, treated with CaCl (1.5%) and GABA (60 mM), peaked at 7.86 units. mg protein min, showing a nearly 2.93-fold increase over the control (2.68 units. mg protein min). A parallel trend was observed for CAT activity. These treatments also reduced petal malondialdehyde content and polyphenol oxidase activity. Protein content and vase life duration increased in all treatments. Plants treated with a combination of GABA (20 mM) and CaCl (0.75%), GABA (60 mM) and CaCl (1.5%), or GABA (40 mM) individually exhibited the longest vase life duration. The co-application of GABA and CaCl improved the antioxidant activity and postharvest quality of cut roses by reducing PPO activity and MDA contents, increasing protein content and prolonging vase life. This treatment is a potential postharvest strategy to improve antioxidant capacity and delay senescence in cut roses.
Topics: Flowers; Calcium Chloride; Antioxidants; gamma-Aminobutyric Acid; Rosa; Superoxide Dismutase; Catalase; Malondialdehyde; Plant Leaves
PubMed: 38914640
DOI: 10.1038/s41598-024-64021-8 -
Scientific Reports Jun 2024In recent decades, the food system has been faced with the significant problem of increasing food waste. Therefore, the feed industry, supported by scientific research,...
In recent decades, the food system has been faced with the significant problem of increasing food waste. Therefore, the feed industry, supported by scientific research, is attempting to valorise the use of discarded biomass as co-products for the livestock sector, in line with EU objectives. In parallel, the search for functional products that can ensure animal health and performances is a common fundamental goal for both animal husbandry and feeding. In this context, camelina cake (CAMC), cardoon cake (CC) and cardoon meal (CM), due valuable nutritional profile, represent prospective alternatives. Therefore, the aim of this work was to investigate the antioxidant activity of CAMC, CC and CM following in vitro digestion using 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), Ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Total phenolic content (TPC) and angiotensin converting enzyme (ACE) inhibitory activity, actively involved in modulating antioxidant properties, were also studied. Further, a peptidomic analysis was adopted to substantiate the presence of bioactive peptides after in vitro digestion. The results obtained confirmed an interesting nutritional profile of CAMC, CC and CM and relevant antioxidant and ACE inhibitory activities. In particular, considering antioxidant profile, CM and CC revealed a significantly higher (10969.80 ± 18.93 mg TE/100 g and 10451.40 ± 149.17 mg TE/100 g, respectively; p < 0.05) ABTS value than CAMC (9511.18 ± 315.29 mg TE/100 g); a trend also confirmed with the FRAP assay (306.74 ± 5.68 mg FeSO/100 g; 272.84 ± 11.02 mg FeSO/100 g; 103.84 ± 3.27 mg FeSO/100 g, for CC, CM and CAMC, respectively). Similar results were obtained for TPC, demonstrating the involvement of phenols in modulating antioxidant activity. Finally, CAMC was found to have a higher ACE inhibitory activity (40.34 ± 10.11%) than the other matrices. Furthermore, potentially bioactive peptides associated with ACE inhibitory, anti-hypertensive, anti-cancer, antimicrobial, antiviral, antithrombotic, DPP-IV inhibitory and PEP-inhibitory activities were identified in CAMC. This profile was broader than that of CC and CM. The presence of such peptides corroborates the antioxidant and ACE profile of the sample. Although the data obtained report the important antioxidant profile of CAMC, CC, and CM and support their possible use, future investigations, particularly in vivo trials will be critical to evaluate and further investigate their effects on the health and performance of farm animals.
Topics: Antioxidants; Cynara; Brassicaceae; Angiotensin-Converting Enzyme Inhibitors; Phenols; Peptides; Animals; Plant Extracts; Animal Feed; Proteomics
PubMed: 38914602
DOI: 10.1038/s41598-024-64989-3 -
Scientific Reports Jun 2024Worldwide industrialization has grown at a rapid pace, contaminating water resources, particularly with phenolic pollutants that pose a risk to aquatic systems and human...
Worldwide industrialization has grown at a rapid pace, contaminating water resources, particularly with phenolic pollutants that pose a risk to aquatic systems and human health. The goal of this study is to create an inexpensive magnetic composite that can effectively remove nitrophenol (o-NP) using adsorptive means. In this instance, a nonanyl chitosan (N-Cs) derivative was synthesized and then combined with activated petroleum coke (AP-coke) and magnetic FeO to boost its adsorbability towards o-NP and to facilitate its separation. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffractometer (XRD), Vibrating sample magnetometer (VSM), X-ray photoelectron spectroscopy (XPS), and zeta potential were employed to characterize the magnetic composite. The experimental results indicated that the FeO/AP-coke/N-Cs composite possesses a greater affinity toward o-NP with a maximal efficiency reached 88% compared to 22.8, 31.2, and 45.8% for FeO, AP-coke and N-Cs, respectively. The equilibrium adsorption data coincided with the Langmuir, Freundlich, and Temkin isotherm models, with a maximum adsorption capacity of 291.55 mg/g at pH 6, whereas the pseudo second order kinetic model offered the best fit to the experimental data. Besides, the developed adsorbent preserved satisfactory adsorption characteristics after reuse for five successive cycles. The proposed adsorption mechanism involves the H-bonding, π-π interaction, hydrophobic interactions and electron donor-acceptor interactions. These findings hypothesize that the constructed magnetic composite could efficiently remove nitrophenols from polluted water with high performance and ease-separation.
PubMed: 38914588
DOI: 10.1038/s41598-024-64117-1 -
Scientific Reports Jun 2024Generally, medicinal plants are harvested with high amount of water, so it is essential to subject the product to drying as soon as possible to prevent degradation...
Generally, medicinal plants are harvested with high amount of water, so it is essential to subject the product to drying as soon as possible to prevent degradation before application. Most compounds from medicinal plants are sensitive to drying processes, so it is important to adjust the drying conditions. The objective of this study was to describe the drying of Rue (Ruta chalepensis L.) leaves, select the models that best fit each drying condition, determine the activation energy and thermodynamic properties of the leaves, and evaluate their quality after drying. Leaves were harvested with moisture content of 3.55 ± 0.05 kg kg and subjected to drying at temperatures of 40, 50, 60 and 70 °C. Valcam model showed the best fit to represent the drying kinetics of Rue leaves at temperatures of 40 and 70 °C, and Midilli model proved to be better for the temperatures of 50 and 60 °C. Effective diffusion coefficient increased linearly with the increase in drying air temperature, and the activation energy was 60.58 kJ mol. Enthalpy, entropy and Gibbs free energy values ranged from 57.973 to 57.723 kJ mol, from - 0.28538 to - 0.28614 kJ mol K and from 147.34 to 155.91 kJ mol, respectively, for the temperature range of 40-70 °C. Drying air temperature promoted darkening or tendency to loss of green color; increase in drying air temperature leads to greater discoloration, as well as a higher concentration of total phenolic compounds (about 221.10 mg GAE mL g dm), with a peak at temperature of 60 °C.
Topics: Plant Leaves; Thermodynamics; Kinetics; Desiccation; Temperature; Water; Plants, Medicinal
PubMed: 38914559
DOI: 10.1038/s41598-024-64418-5 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Jun 2024α-arbutin has important applications in cosmetics and medicine. However, the extraction yield from plant tissues is relatively low, which restricts its application...
α-arbutin has important applications in cosmetics and medicine. However, the extraction yield from plant tissues is relatively low, which restricts its application value. In this study, we investigated the synthesis of α-arbutin using maltodextrin as the donor and hydroquinone as the acceptor, using a cyclodextrin glucosyltransferase (CGTase) from . We performed site-saturated and site-directed mutagenesis on CGTase. The activity of the variant CGTase-F235G-N166H was 3.48 times higher than that of the wild type. Moreover, we achieved a conversion rate of 63% by optimizing the reaction pH, temperature, and hydroquinone addition amount. Overall, this study successfully constructed a strain with improved conversion rate for the synthetic production of α-arbutin and hydroquinone. These findings have significant implications for reducing the industrial production cost of α-arbutin and enhancing the conversion rate of the product.
Topics: Glucosyltransferases; Arbutin; Hydroquinones; Mutagenesis, Site-Directed; Polysaccharides
PubMed: 38914495
DOI: 10.13345/j.cjb.230693