-
Plant Physiology Jun 2024Bacterial wilt severely jeopardizes plant growth and causes enormous economic loss in the production of many crops, including tobacco (Nicotiana tabacum). Here, we first...
Bacterial wilt severely jeopardizes plant growth and causes enormous economic loss in the production of many crops, including tobacco (Nicotiana tabacum). Here, we first demonstrated that the roots of bacterial wilt-resistant tobacco mutant KCB-1 can limit the growth and reproduction of Ralstonia solanacearum. Secondly, we demonstrated that KCB-1 specifically induced an upregulation of naringenin content in root metabolites and root secretions. Further experiments showed that naringenin can disrupt the structure of R. solanacearum, inhibit the growth and reproduction of R. solanacearum, and exert a controlling effect on bacterial wilt. Exogenous naringenin application activated the resistance response in tobacco by inducing the burst of reactive oxygen species and salicylic acid deposition, leading to transcriptional reprogramming in tobacco roots. Additionally, both external application of naringenin in CB-1 and overexpression of the Nicotiana tabacum chalcone isomerase (NtCHI) gene, which regulates naringenin biosynthesis, in CB-1 resulted in a higher complexity of their inter-root bacterial communities than in untreated CB-1. Further analysis showed that naringenin could be used as a marker for resistant tobacco. The present study provides a reference for analyzing the resistance mechanism of bacterial wilt-resistant tobacco and controlling tobacco bacterial wilt.
Topics: Ralstonia solanacearum; Nicotiana; Flavanones; Plant Diseases; Plant Roots; Mutation; Disease Resistance; Gene Expression Regulation, Plant; Reactive Oxygen Species; Salicylic Acid
PubMed: 38573326
DOI: 10.1093/plphys/kiae185 -
Endocrine Practice : Official Journal... Jun 2024This study evaluates the impact of a representative proton pump inhibitor (PPI) (omeprazole), administered simultaneously or staggered, on the pharmacokinetics of... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study evaluates the impact of a representative proton pump inhibitor (PPI) (omeprazole), administered simultaneously or staggered, on the pharmacokinetics of levothyroxine (LT4) solution (Tirosint-SOL).
METHODS
This was a randomized, 3-way crossover, comparative bioavailability study in 36 healthy adults under fasting conditions. Omeprazole 40 mg delayed-release capsule was administered once daily from Day 1 to 6 (mornings, Treatment-A; evenings, Treatment-B; none, Treatment-C) to increase and stabilize gastric pH. In the morning of Day 5, a single dose of LT4 solution 600 mcg was administered. Blood samples were collected 0 to 48 hours post-LT4 administration. Noncompartmental pharmacokinetic parameters were calculated for total serum thyroxine using baseline-corrected data. Maximum concentration (C) and area under the concentration-time curve (AUC) were included in an analysis of variance to obtain geometric mean ratios and 90% confidence intervals.
RESULTS
For both comparisons (A/C and B/C), geometric mean ratios and 90% confidence intervals for all parameters were within the equivalence boundaries (80%-125%), indicating bioequivalence: for A/C, AUC 98.98% [94%-104%], and C 91.68% [87%-97%]; for B/C, AUC 98.94% [95%-103%], and C 94.90% [90%-100%]. Median T (time associated with Cmax) was similar across treatments.
CONCLUSION
This study demonstrated that Tirosint-SOL bioavailability is unaffected by coadministration of a representative PPI, given simultaneously or staggered by about 12 hours, compared to administration of LT4 solution alone. For hypothyroid patients on PPI therapy, administration of LT4 solution may reduce variations in thyroid stimulating hormone levels related to intermittent use of acid-reducing drugs and consequently the need for dose adjustments.
Topics: Humans; Proton Pump Inhibitors; Male; Thyroxine; Adult; Biological Availability; Cross-Over Studies; Female; Middle Aged; Omeprazole; Young Adult; Drug Interactions
PubMed: 38554774
DOI: 10.1016/j.eprac.2024.03.388 -
International Journal of Molecular... Mar 2024We tested five chemically and metabolically stable prostaglandin (PG) receptor agonists in a mouse model of dexamethasone-induced ocular hypertension (OHT). Whilst all...
We tested five chemically and metabolically stable prostaglandin (PG) receptor agonists in a mouse model of dexamethasone-induced ocular hypertension (OHT). Whilst all compounds significantly ( < 0.05, ANOVA) lowered intraocular pressure (IOP) after twice-daily bilateral topical ocular dosing (5 µg/dose) over three weeks, the time course and magnitude of the responses varied. The onset of action of NS-304 (IP-PG receptor agonist) and rivenprost (EP4-PG receptor agonist) was slower than that of misoprostol (mixed EP2/EP3/EP4-PG receptor agonist), PF-04217329 (EP2-PG receptor agonist), and butaprost (EP2-PG receptor agonist). The rank order of IOP-lowering efficacies aligned with the onset of actions of these compounds. Peak IOP reductions relative to vehicle controls were as follows: misoprostol (74.52%) = PF-04217329 (74.32%) > butaprost (65.2%) > rivenprost (58.4%) > NS-304 (55.3%). A literature survey indicated that few previously evaluated compounds (e.g., latanoprost, timolol, pilocarpine, brimonidine, dorzolamide, cromakalim analog (CKLP1), losartan, tissue plasminogen activator, trans-resveratrol, sodium 4-phenyl acetic acid, etc.) in various animal models of steroid-induced OHT were able to match the effectiveness of misoprostol, PF-04217329 or butaprost. Since a common feature of the latter compounds is their relatively high affinity and potency at the EP2-PG receptor sub-type, which activates the production of intracellular cAMP in target cells, our studies suggest that drugs selective for the EP2-PG receptor may be suited to treat corticosteroid-induced OHT.
Topics: Animals; Mice; Misoprostol; Tissue Plasminogen Activator; Ocular Hypertension; Receptors, Prostaglandin; Receptors, Prostaglandin E, EP4 Subtype; Steroids; Acetamides; Acetates; Pyrazines; Sulfonamides
PubMed: 38542305
DOI: 10.3390/ijms25063328 -
Medicina (Kaunas, Lithuania) Mar 2024The enteric form of omeprazole is one of the most commonly prescribed medications. Similarly to Europe, Kazakhstan relies on the localization of pharmaceutical drug...
The enteric form of omeprazole is one of the most commonly prescribed medications. Similarly to Europe, Kazakhstan relies on the localization of pharmaceutical drug production as one of its primary strategies to ensure that its population has access to affordable and good-quality medicines. This study comprehensively describes the technologically available development of bioequivalent delayed-release omeprazole. Various regimes and technological parameters were tested on laboratory- and production-scale equipment to establish a technical process where a functional and gastro-protective layer is essential. According to the ICH guidance on stability testing and Kazakhstan local rules, stability studies were conducted under conditions appropriate for climate zone II. The comparison of the rate and extent of absorption with subsequent assessment of the bioequivalence of the generic and reference drugs after a single dose of each drug at a dose of 40 mg was performed. The quantitative and qualitative composition and technology of producing a new generic enteric form of omeprazole in capsules were developed and implemented at the manufacturing site of solid forms. Dissolution profiles in media with pH 1.2 and 6.8 were proven. During the accelerated six-month and long-term twelve-month studies, the developed formulation in both packaging materials at each control point passed the average weight and mass uniformity test, dissolution test, acid-resistance stage test, buffer stage test, impurity assay, and microbiological purity test and met all the specification criteria. A bioequivalence study in 24 healthy volunteers compared against the innovative drug showed the bioequivalency of the new generic system. The obtained values from the test and reference products were 1321 ± 249.0 ng/mL and 1274 ± 233 ng/mL for C, 4521 ± 841 ng·h /mL and 4371 ± 695 ng·h /mL for AUC, and 4636 ± 814 ng·h /mL and 4502 ± 640 ng·h /mL for AUC. Using affordable technologies, a bioequivalent generic delayed-release formulation of 20 and 40 mg omeprazole has been developed.
Topics: Humans; Omeprazole; Therapeutic Equivalency; Capsules; Cross-Over Studies; Europe
PubMed: 38541153
DOI: 10.3390/medicina60030427 -
Marine Drugs Feb 2024A biocompatible, heterogeneous, fucose-rich, sulfated polysaccharide (fucoidan) is biosynthesized in brown seaweed. In this study, fucoidan was isolated from (PAC)...
Investigation of Physical Characteristics and In Vitro Anti-Inflammatory Effects of Fucoidan from : A Comprehensive Assessment against Lipopolysaccharide-Induced Inflammation.
A biocompatible, heterogeneous, fucose-rich, sulfated polysaccharide (fucoidan) is biosynthesized in brown seaweed. In this study, fucoidan was isolated from (PAC) using celluclast-assisted extraction, purified, and evaluated for its anti-inflammatory potential in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Structural analyses were performed using Fourier transform infrared (FTIR) and scanning electron microscopy. Among the purified fucoidans, fucoidan fraction 5 (F5) exhibited strong inhibitory activity against LPS-induced nitric oxide (NO) production and pro-inflammatory cytokine generation through the regulation of iNOS/COX-2, MAPK, and NF-κB signaling in LPS-induced RAW 264.7 cells. Determination of the structural characteristics indicated that purified F5 exhibited characteristics similar to those of commercial fucoidan. In addition, further analyses suggested that F5 inhibits LPS-induced toxicity, cell death, and NO generation in zebrafish models. Taken together, these findings imply that fucoidans have exceptional anti-inflammatory action, both in vitro and in vivo, and that they may have prospective uses in the functional food sector.
Topics: Animals; Lipopolysaccharides; Zebrafish; Polysaccharides; Inflammation; Phaeophyceae; Nitric Oxide
PubMed: 38535450
DOI: 10.3390/md22030109 -
International Journal of Pharmaceutics Apr 2024The current investigation emphasizes the use of fucoidan and sericin as dual-role biomaterials for obtaining novel nanohybrid systems for the delivery of diclofenac...
The current investigation emphasizes the use of fucoidan and sericin as dual-role biomaterials for obtaining novel nanohybrid systems for the delivery of diclofenac sodium (DS) and the potential treatment of chronic inflammatory diseases. The innovative formulations containing 4 mg/ml of fucoidan and 3 mg/ml of sericin showed an average diameter of about 200 nm, a low polydispersity index (0.17) and a negative surface charge. The hybrid nanosystems demonstrated high stability at various pHs and temperatures, as well as in both saline and glucose solutions. The Rose Bengal assay evidenced that fucoidan is the primary modulator of relative surface hydrophobicity with a two-fold increase of this parameter when compared to sericin nanoparticles. The interaction between the drug and the nanohybrids was confirmed through FT-IR analysis. Moreover, the release profile of DS from the colloidal systems showed a prolonged and constant drug leakage over time both at pH 5 and 7. The DS-loaded nanohybrids (DIFUCOSIN) induced a significant decrease of IL-6 and IL-1β with respect to the active compound in human chondrocytes evidencing a synergistic action of the individual components of nanosystems and the drug and demonstrating the potential application of the proposed nanomedicine for the treatment of inflammation.
Topics: Humans; Diclofenac; Sericins; Spectroscopy, Fourier Transform Infrared; Nanoparticles; Pharmaceutical Preparations; Sodium Chloride; Polysaccharides
PubMed: 38531433
DOI: 10.1016/j.ijpharm.2024.124034 -
Obesity Surgery May 2024To evaluate the influence of anisodamine injection at the Zusanli (ST36) on early postoperative recovery quality in patients who have undergone laparoscopic sleeve... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate the influence of anisodamine injection at the Zusanli (ST36) on early postoperative recovery quality in patients who have undergone laparoscopic sleeve gastrectomy.
MATERIALS AND METHODS
141 patients undergoing laparoscopic sleeve gastrectomy were randomly divided into the control group (group C), the normal saline group (group S) and the anisodamine group (group A). Acupuncture point injections were administered after induction of general anesthesia. The quality of recovery-40 questionnaire (QoR-40) scores were documented preoperatively (D0) and on the 1st (D1), 3rd (D3) and 7th (D7) days postoperatively. Additional metrics included: the numerical rating scale (NRS) for pain, postoperative nausea and vomiting (PONV), assessment and analgesic consumption 24-h post-extubation and the initial postoperative times for ambulation and anal exhaust. Substance P (SP), β-endorphin (β-EP), motilin (MTL) and gastrin (GAS) were quantified at 24-h post-surgery.
RESULTS
Compared with group C, group A demonstrated an elevation in QoR-40 scores and physical comfort dimensions during D1-3, and an increased pain scores during D1-7; group S exhibited an augmentation in QoR-40 scores and pain scores on D1 (p < 0.05). Compared with group S, group A improved QoR-40 scores on D1 and pain scores during D1-3 (p < 0.05). SP, β-EP, MTL and GAS presented significant variances among the groups 24-h post-surgery (p < 0.05). There were significant differences between the groups in NRS pain scores and PONV scores at 24-h postoperatively, dosage of dizocin on the first postoperative day, and time to first anal defecation (p < 0.05).
CONCLUSION
The administration of anisodamine via ST36 acupoint injections has been demonstrated to facilitate the recuperation of gastrointestinal functionality, to alleviate postoperative pain and nausea, and substantially to enhance the quality of early postoperative recovery.
Topics: Humans; Postoperative Nausea and Vomiting; Acupuncture Points; Obesity, Morbid; Pain, Postoperative; Bariatric Surgery; Laparoscopy; Solanaceous Alkaloids
PubMed: 38507149
DOI: 10.1007/s11695-024-07182-9 -
Acta Obstetricia Et Gynecologica... Jun 2024Labor induction rates have increased over the last decades, and in many high-income countries, more than one in four labors are induced. Outpatient management of labor...
INTRODUCTION
Labor induction rates have increased over the last decades, and in many high-income countries, more than one in four labors are induced. Outpatient management of labor induction has been suggested in low-risk pregnancies to improve women's birth experiences while also promoting a more efficient use of healthcare resources. The primary aim of this paper was to assess the proportion of women in a historical cohort that would have been eligible for outpatient labor induction with oral misoprostol. Second, we wanted to report safety outcomes and assess efficacy outcomes for mothers and infants in pregnancies that met the criteria for outpatient care.
MATERIAL AND METHODS
Criteria for outpatient labor induction with oral misoprostol were applied to a historical cohort of women with induction of labor at two Norwegian tertiary hospitals in the period January 1, through July 31, 2021. The criteria included low-risk women with an unscarred uterus expecting a healthy, singleton baby in cephalic position at term. The primary outcome was the proportion of women eligible for outpatient labor induction. Secondary outcomes included reasons for ineligibility and, for eligible women, safety and efficacy outcomes.
RESULTS
Overall, 29.7% of the 1320 women who underwent labor induction in a singleton term pregnancy met the criteria for outpatient labor induction. We identified two serious adverse events that potentially could have occurred outside the hospital if the women had received outpatient care. The mean duration from initiation of labor induction to administration of the last misoprostol was 22.4 h. One in 14 multiparous women gave birth within 3 h after the last misoprostol dose.
CONCLUSIONS
In this historical cohort, three in ten women met the criteria for outpatient management of labor induction with oral misoprostol. Serious adverse events were rare. The average time span from the initiation of labor induction to the last misoprostol was nearly 24 h. This suggests a potential for low-risk women with an induced labor to spend a substantial period of time at home before labor onset. However, larger studies testing or evaluating labor induction with oral misoprostol as an outpatient procedure are needed to draw conclusions.
Topics: Humans; Labor, Induced; Female; Pregnancy; Misoprostol; Adult; Oxytocics; Cohort Studies; Ambulatory Care; Norway
PubMed: 38504457
DOI: 10.1111/aogs.14799 -
Journal of Nanobiotechnology Mar 2024Endocrine therapy is standard for hormone receptor-positive (HR) breast cancer treatment. However, current strategies targeting estrogen signaling pay little attention...
Endocrine therapy is standard for hormone receptor-positive (HR) breast cancer treatment. However, current strategies targeting estrogen signaling pay little attention to estradiol metabolism in the liver and is usually challenged by treatment failure. In a previous study, we demonstrated that the natural compound naringenin (NAR) inhibited HR breast cancer growth by activating estrogen sulfotransferase (EST) expression in the liver. Nevertheless, the poor water solubility, low bio-barrier permeability, and non-specific distribution limited its clinical application, particularly for oral administration. Here, a novel nano endocrine drug NAR-cell penetrating peptide-galactose nanoparticles (NCG) is reported. We demonstrated that NCG presented specific liver targeting and increased intestinal barrier permeability in both cell and zebrafish xenotransplantation models. Furthermore, NCG showed liver targeting and enterohepatic circulation in mouse breast cancer xenografts following oral administration. Notably, the cancer inhibition efficacy of NCG was superior to that of both NAR and the positive control tamoxifen, and was accompanied by increased hepatic EST expression and reduced estradiol levels in the liver, blood, and tumor tissue. Moreover, few side effects were observed after NCG treatment. Our findings reveal NCG as a promising candidate for endocrine therapy and highlight hepatic EST targeting as a novel therapeutic strategy for HR breast cancer.
Topics: Humans; Mice; Animals; Female; Breast Neoplasms; Zebrafish; Receptors, Estrogen; Estrogens; Tamoxifen; Estradiol; Liver; Nanoparticles; Flavanones
PubMed: 38504208
DOI: 10.1186/s12951-024-02356-0 -
The Israel Medical Association Journal... Mar 2024
Topics: Humans; Gastric Bypass; Misoprostol; Anastomosis, Surgical; Obesity, Morbid; Laparoscopy; Anastomotic Leak
PubMed: 38493332
DOI: No ID Found