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BMC Cancer Jun 2024Evaluation publications typically summarize the results of studies to demonstrate the effectiveness of an intervention, but little is shared concerning any changes... (Randomized Controlled Trial)
Randomized Controlled Trial
Process evaluation protocol plan for a home-based physical activity intervention versus educational intervention for persistent taxane-induced peripheral neuropathy (B-HAPI study): a randomized controlled trial.
BACKGROUND
Evaluation publications typically summarize the results of studies to demonstrate the effectiveness of an intervention, but little is shared concerning any changes implemented during the study. We present a process evaluation protocol of a home-based gait, balance, and resistance exercise intervention to ameliorate persistent taxane-induced neuropathy study according to 7 key elements of process evaluation.
METHODS
The process evaluation is conducted parallel to the longitudinal, randomized control clinical trial examining the effects of the home-based gait, balance, and resistance exercise program for women with persistent peripheral neuropathy following treatment with taxanes for breast cancer (IRB approval: Pro00040035). The flowcharts clarify how the intervention should be implemented in comparable settings, fidelity procedures help to ensure the participants are comfortable and identify their individual needs, and the process evaluation allows for the individual attention tailoring and focus of the research to avoid protocol deviation.
CONCLUSIONS
The publication of the evaluation protocol plan adds transparency to the findings of clinical trials and favors process replication in future studies. The process evaluation enables the team to systematically register information and procedures applied during recruitment and factors that impact the implementation of the intervention, thereby allowing proactive approaches to prevent deviations from the protocol. When tracking an intervention continuously, positive or negative intervention effects are revealed early on in the study, giving valuable insight into inconsistent results. Furthermore, a process evaluation adds a participant-centered element to the research protocols, which allows a patient-centered approach to be applied to data collection.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04621721, November 9, 2020, registered prospectively.
PROTOCOL VERSION
April 27, 2020, v2.
Topics: Humans; Peripheral Nervous System Diseases; Female; Breast Neoplasms; Taxoids; Exercise Therapy; Patient Education as Topic; Exercise; Bridged-Ring Compounds; Longitudinal Studies; Research Design; Randomized Controlled Trials as Topic
PubMed: 38937667
DOI: 10.1186/s12885-024-12444-x -
PloS One 2024Mucosal-delivered drugs have to pass through the mucus layer before absorption through the epithelial cell membrane. Although there has been increasing interest in...
Mucosal-delivered drugs have to pass through the mucus layer before absorption through the epithelial cell membrane. Although there has been increasing interest in polymeric mucins, a major structural component of mucus, potentially acting as important physiological regulators of mucosal drug absorption, there are no reports that have systematically evaluated the interaction between mucins and drugs. In this study, we assessed the potential interaction between human polymeric mucins (MUC2, MUC5B, and MUC5AC) and various drugs with different chemical profiles by simple centrifugal method and fluorescence analysis. We found that paclitaxel, rifampicin, and theophylline likely induce the aggregation of MUC5B and/or MUC2. In addition, we showed that the binding affinity of drugs for polymeric mucins varied, not only between individual drugs but also among mucin subtypes. Furthermore, we demonstrated that deletion of MUC5AC and MUC5B in A549 cells increased the cytotoxic effects of cyclosporin A and paclitaxel, likely due to loss of mucin-drug interaction. In conclusion, our results indicate the necessity to determine the binding of drugs to mucins and their potential impact on the mucin network property.
Topics: Humans; Paclitaxel; Mucin 5AC; A549 Cells; Drug Interactions; Mucin-5B; Mucins; Mucin-2; Rifampin; Cyclosporine; Protein Binding
PubMed: 38935605
DOI: 10.1371/journal.pone.0306058 -
Nutrients Jun 2024The relationship between vitamin A supplementation and myopia has been a topic of debate, with conflicting and inconclusive findings. We aimed to determine whether there... (Meta-Analysis)
Meta-Analysis
The relationship between vitamin A supplementation and myopia has been a topic of debate, with conflicting and inconclusive findings. We aimed to determine whether there is a causal relationship between vitamin A supplementation and the risk of myopia using Mendelian randomization (MR) and meta-analytical methods. Genetic variants from the UK Biobank and FinnGen studies associated with the response to vitamin A supplementation were employed as instrumental variables to evaluate the causal relationship between vitamin A supplementation and myopia. Fixed-effects meta-analysis was then used to combine MR estimates from multiple sources for each outcome. The meta-analysis of MR results found no convincing evidence to support a direct causal relationship between vitamin A supplementation and myopia risk (odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.82-1.20, = 0%, = 0.40). The analysis of three out of the four sets of MR analyses indicated no direction of causal effect, whereas the other set of results suggested that higher vitamin A supplementation was associated with a lower risk of myopia (OR = 0.002, 95% CI 1.17 × 10-3.099, = 0.096). This comprehensive MR study and meta-analysis did not find valid evidence of a direct association between vitamin A supplementation and myopia. Vitamin A supplementation may not have an independent effect on myopia, but intraocular processes associated with vitamin A may indirectly contribute to its development.
Topics: Humans; Myopia; Mendelian Randomization Analysis; Vitamin A; Dietary Supplements; Polymorphism, Single Nucleotide; Risk Factors; Odds Ratio
PubMed: 38931287
DOI: 10.3390/nu16121933 -
Nutrients Jun 2024Stroke is the world's second-leading cause of death. Current treatments for cerebral edema following intracerebral hemorrhage (ICH) mainly involve hyperosmolar fluids,...
Stroke is the world's second-leading cause of death. Current treatments for cerebral edema following intracerebral hemorrhage (ICH) mainly involve hyperosmolar fluids, but this approach is often inadequate. Propolis, known for its various beneficial properties, especially antioxidant and anti-inflammatory properties, could potentially act as an adjunctive therapy and help alleviate stroke-associated injuries. The chemical composition of propolis extract was analyzed by GC-MS after derivatization for its total phenolic and total flavonoid content. The total phenolic content and total flavonoid content of the propolis extract were 1037.31 ± 24.10 μg GAE/mL and 374.02 ± 3.36 μg QE/mL, respectively. By GC-MS analysis, its major constituents were found to be triterpenoids (22.4% of TIC). Minor compounds, such as phenolic lipids (6.7% of TIC, GC-MS) and diterpenic acids (2.3% of TIC, GC-MS), were also found. Ninety-six Sprague Dawley rats were divided into six groups; namely, the control group, the ICH group, and four ICH groups that received the following therapies: mannitol, propolis extract (daily oral propolis administration after the ICH induction), propolis-M (propolis and mannitol), and propolis-B+A (daily oral propolis administration 7 days prior to and 72 h after the ICH induction). Neurocognitive functions of the rats were analyzed using the rotarod challenge and Morris water maze. In addition, the expression of NF-κB, SUR1-TRPM4, MMP-9, and Aquaporin-4 was analyzed using immunohistochemical methods. A TUNEL assay was used to assess the percentage of apoptotic cells. Mannitol significantly improved cognitive-motor functions in the ICH group, evidenced by improved rotarod and Morris water maze completion times, and lowered SUR-1 and Aquaporin-4 levels. It also significantly decreased cerebral edema by day 3. Similarly, propolis treatments (propolis-A and propolis-B+A) showed comparable improvements in these tests and reduced edema. Moreover, combining propolis with mannitol (propolis-M) further enhanced these effects, particularly in reducing edema and the Virchow-Robin space. These findings highlight the potential of propolis from the Indonesian stingless bee, , from the Central Tapanuli region as a neuroprotective, adjunctive therapy.
Topics: Animals; Propolis; Neuroprotective Agents; Cerebral Hemorrhage; Rats, Sprague-Dawley; Bees; Disease Models, Animal; Rats; Male; Flavonoids; Antioxidants; Brain Edema; Gas Chromatography-Mass Spectrometry; Phenols
PubMed: 38931235
DOI: 10.3390/nu16121880 -
Nutrients Jun 2024Cardiovascular diseases (CVD) are the leading cause of death worldwide, influenced by the interaction of factors, including age, sex, genetic conditions,...
Cardiovascular diseases (CVD) are the leading cause of death worldwide, influenced by the interaction of factors, including age, sex, genetic conditions, overweight/obesity, hypertension, an abnormal lipid profile, vitamin deficiencies, diabetes, and psychological factors. This study aimed to assess the relationships between psychosocial and nutritional factors in a group of 61 patients with CVD (i.e., atherosclerosis, hypertension, ischemic heart disease, and myocardial infarction) and their possible impact on the course of the disease. The plasma concentrations of vitamins A, E, D, and β-carotene were determined using validated HPLC-MS/MS, while the lipid profile was analyzed enzymatically. Psychosocial factors and nutritional behaviors were assessed using author-designed questionnaires. Over 50% of patients had 25-OH-D3 and retinol deficiencies, while >85% of patients exhibited significant deficiencies in α-tocopherol and β-carotene. The lipid profile showed no specific relationship with any particular CVD. Dietary behavior minimally impacted biochemical parameters except for higher β-carotene concentrations in the group with higher fruit and vegetable intake. The negative impact of the CVD on selected parameters of quality of life was noticed. To increase the effectiveness of the prevention and treatment of CVD, the need for interdisciplinary cooperation observed between doctors, psychologists, and specialists in human nutrition seems to be justified.
Topics: Humans; Female; Male; Middle Aged; Cardiovascular Diseases; Aged; Vitamins; Nutritional Status; beta Carotene; Quality of Life; Adult; Vitamin A; Feeding Behavior; Diet; Lipids; Vitamin E
PubMed: 38931221
DOI: 10.3390/nu16121866 -
Nutrients Jun 2024Patients with chronic kidney disease (CKD) suffer disproportionately from a high burden of cardiovascular disease, which, despite recent scientific advances, remains... (Review)
Review
Patients with chronic kidney disease (CKD) suffer disproportionately from a high burden of cardiovascular disease, which, despite recent scientific advances, remains partly understood. Vascular calcification (VC) is the result of an ongoing process of misplaced calcium in the inner and medial layers of the arteries, which has emerged as a critical contributor to cardiovascular events in CKD. Beyond its established role in blood clotting and bone health, vitamin K appears crucial in regulating VC via vitamin K-dependent proteins (VKDPs). Among these, the matrix Gla protein (MGP) serves as both a potent inhibitor of VC and a valuable biomarker (in its inactive form) for reflecting circulating vitamin K levels. CKD patients, especially in advanced stages, often present with vitamin K deficiency due to dietary restrictions, medications, and impaired intestinal absorption in the uremic environment. Epidemiological studies confirm a strong association between vitamin K levels, inactive MGP, and increased CVD risk across CKD stages. Based on the promising results of pre-clinical data, an increasing number of clinical trials have investigated the potential benefits of vitamin K supplementation to prevent, delay, or even reverse VC, but the results have remained inconsistent.
Topics: Humans; Vascular Calcification; Vitamin K; Renal Insufficiency, Chronic; Matrix Gla Protein; Vitamin K Deficiency; Extracellular Matrix Proteins; Calcium-Binding Proteins; Dietary Supplements; Cardiovascular Diseases; Biomarkers
PubMed: 38931153
DOI: 10.3390/nu16121798 -
Molecules (Basel, Switzerland) Jun 2024This review collects the synthetic modifications performed on andrographolide, a natural molecule derived from , for oncology applications. Various pharmacomodulations... (Review)
Review
This review collects the synthetic modifications performed on andrographolide, a natural molecule derived from , for oncology applications. Various pharmacomodulations were carried out, and the products were tested on different cancer cell lines. The impact of these modifications was analyzed with the aim of mapping the positions essential for activity to facilitate future research in this field. However, this study makes it clear that, in addition to structural modifications of the molecule, which can result in varying degrees of effectiveness in targeting interactions, the lipophilic capacity of the structures obtained through hemisynthesis is of significant importance.
Topics: Diterpenes; Humans; Antineoplastic Agents; Structure-Activity Relationship; Neoplasms; Andrographis; Cell Line, Tumor; Molecular Structure; Animals
PubMed: 38930949
DOI: 10.3390/molecules29122884 -
Molecules (Basel, Switzerland) Jun 2024Four new diterpenoids, isodosins A-D (-), together with nine known compounds (-) were isolated and identified from the aerial parts of (Maxim.) Hara. The structures of...
Four new diterpenoids, isodosins A-D (-), together with nine known compounds (-) were isolated and identified from the aerial parts of (Maxim.) Hara. The structures of the new diterpenoids were elucidated based on the analysis of HR-ESI-MS data, 1D/2D-NMR-spectroscopic data, and electronic circular dichroism (ECD) calculations. Cytotoxicities of compounds , , , , and against the HepG2 and H1975 cell lines were evaluated with the MTT assay. As a result, compounds , , and revealed higher levels of cytotoxicity against HepG2 cells than against H1975 cells. Moreover, compund demonstrated the most efficacy in inhibiting the proliferation of HepG2 cells, with an IC value of 41.13 ± 3.49 μM. This effect was achieved by inducing apoptosis in a dose-dependent manner. Furthermore, the relationships between the structures and activities of these compounds are briefly discussed.
Topics: Humans; Diterpenes; Isodon; Plant Components, Aerial; Antineoplastic Agents, Phytogenic; Apoptosis; Hep G2 Cells; Molecular Structure; Cell Line, Tumor; Cell Proliferation; Plant Extracts; Structure-Activity Relationship; Cell Survival; Drug Screening Assays, Antitumor
PubMed: 38930799
DOI: 10.3390/molecules29122733 -
Molecules (Basel, Switzerland) Jun 2024Seven new abietane diterpenoids, comprising medusanthol A-G (-, , -) and two previously identified analogs ( and ), were isolated from the hexane extract of the aerial...
Seven new abietane diterpenoids, comprising medusanthol A-G (-, , -) and two previously identified analogs ( and ), were isolated from the hexane extract of the aerial parts of The structures of the compounds were elucidated by HRESIMS, 1D/2D NMR spectroscopic data, IR spectroscopy, NMR calculations with DP4+ probability analysis, and ECD calculations. The anti-neuroinflammatory potential of compounds - was evaluated by determining their ability to inhibit the production of nitric oxide (NO) and the proinflammatory cytokine TNF-α in BV2 microglia stimulated with LPS and IFN-γ. Compounds - and exhibited decreased NO levels at a concentration of 12.5 µM. Compound demonstrated strong activity with an IC of 3.12 µM, and compound had an IC of 15.53 µM; both compounds effectively reduced NO levels compared to the positive control quercetin (IC 11.8 µM). Additionally, both compounds significantly decreased TNF-α levels, indicating their potential as promising anti-neuroinflammatory agents.
Topics: Abietanes; Anti-Inflammatory Agents; Animals; Nitric Oxide; Mice; Microglia; Tumor Necrosis Factor-alpha; Plant Extracts; Cell Line; Molecular Structure; Lipopolysaccharides; Plant Components, Aerial
PubMed: 38930790
DOI: 10.3390/molecules29122723 -
Microorganisms May 2024Stevioside is a secondary metabolite of diterpenoid glycoside production in plants. It has been used as a natural sweetener in various foods because of its high...
Stevioside is a secondary metabolite of diterpenoid glycoside production in plants. It has been used as a natural sweetener in various foods because of its high sweetness and low-calorie content. In this study, we constructed a strain for the complete synthesis of stevioside using a metabolic engineering strategy. Firstly, the synthesis pathway of steviol was modularly constructed in BY4742, and the precursor pathway was strengthened. The yield of steviol was used as an indicator to investigate the expression effect of different sources of diterpene synthases under different combinations, and the strains with further improved steviol yield were screened. Secondly, glycosyltransferases were heterologously expressed in this strain to produce stevioside, the sequence of glycosyltransferase expression was optimized, and the uridine diphosphate-glucose (UDP-Glc) supply was enhanced. Finally, the results showed that the strain SST-302III-ST2 produced 164.89 mg/L of stevioside in a shake flask experiment, and the yield of stevioside reached 1104.49 mg/L in an experiment employing a 10 L bioreactor with batch feeding, which was the highest yield reported. We constructed strains with a high production of stevioside, thus laying the foundation for the production of other classes of steviol glycosides and holding good prospects for application and promotion.
PubMed: 38930507
DOI: 10.3390/microorganisms12061125