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Nature Communications Jul 2024Statin drugs lower blood cholesterol levels for cardiovascular disease prevention. Women are more likely than men to experience adverse statin effects, particularly...
Statin drugs lower blood cholesterol levels for cardiovascular disease prevention. Women are more likely than men to experience adverse statin effects, particularly new-onset diabetes (NOD) and muscle weakness. Here we find that impaired glucose homeostasis and muscle weakness in statin-treated female mice are associated with reduced levels of the omega-3 fatty acid, docosahexaenoic acid (DHA), impaired redox tone, and reduced mitochondrial respiration. Statin adverse effects are prevented in females by administering fish oil as a source of DHA, by reducing dosage of the X chromosome or the Kdm5c gene, which escapes X chromosome inactivation and is normally expressed at higher levels in females than males. As seen in female mice, we find that women experience more severe reductions than men in DHA levels after statin administration, and that DHA levels are inversely correlated with glucose levels. Furthermore, induced pluripotent stem cells from women who developed NOD exhibit impaired mitochondrial function when treated with statin, whereas cells from men do not. These studies identify X chromosome dosage as a genetic risk factor for statin adverse effects and suggest DHA supplementation as a preventive co-therapy.
Topics: Animals; Female; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Mice; Mitochondria; Humans; X Chromosome; Docosahexaenoic Acids; Induced Pluripotent Stem Cells; Gene Dosage; Mice, Inbred C57BL; Blood Glucose; Glucose; Diabetes Mellitus
PubMed: 38956041
DOI: 10.1038/s41467-024-49764-2 -
Environmental Science and Pollution... Jul 2024The removal of dyes from the aquatic ecosystem is necessary being a major threat to life. For enhanced remediation of methylene blue (MB) dye, a new ternary...
The removal of dyes from the aquatic ecosystem is necessary being a major threat to life. For enhanced remediation of methylene blue (MB) dye, a new ternary biopolymer-geopolymer-surfactant composite adsorbent is synthesized by combining phosphoric acid geopolymer (PAGP), calcium alginate (Alg), and sodium lauryl sulfate (SLS). During the synthesis of the composites, PAGP and SLS were mixed with the alginate matrix, producing porous hybrid beads. The PAGP-SLS-alginate (PSA) beads prepared were characterized using different analytical tools, i.e., scanning electron microscopy (SEM), Fourier transform infrared spectrophotometry (FTIR), X-ray diffractometry (XRD), surface area and porosimetery (SAP), and thermogravimetric analysis (TGA). To ascertain the ideal conditions for the adsorption process, a batch reactor procedure was used to investigate the effects of several parameters on MB adsorption, including pH (2, 4, 6, 8, 10), PSA adsorbent dosage (0.06-0.12 g), MB concentration (50-500 mg/L), contact time (15 to 300 min), and temperature (25, 35, and 45 °C). The SEM investigation indicated that ~ 1860 μm-sized PSA beads with 6-8 μm voids are generated. Based on XRD, FTIR, and SAP examinations, the material is amorphous, having numerous functional groups and an average pore size of 6.42 nm. Variation of pH has a little effect on the adsorption process, and the pH of 7.44 was found to be the pH of the PSA beads. According to the findings of the batch study, equilibrium adsorption was obtained in 270-300 min, showing that the adsorption process was moderately slow-moving and effective. The dye adsorption linearly increased with initial dye concentration over concentration range of 50-500 mg/L and reciprocally decreased with rise in temperature. 0.06 g adsorbent dose, 25 °C, pH10, and 270 min were found to be the better conditions for adsorption experiments. Langmuir isotherm fitted well compared to Freundlich, Temkin, and Dubinin-Radushkevich (DR) isotherm models on the experimental data, and the maximum adsorption capacity(q) calculated was 1666.6 mg. g. Pseudo-second-order (PSO) kinetics model and multi steps (two) intra particle diffusion (IPD) model fitted well on the adsorption kinetics data. The system's entropy, Gibbs free energy, and change in enthalpy were measured and found to be -109.171 J. mol. K, - 8.198 to - 6.014 kJ. mol, and - 40.747 kJ. mol. Thermodynamics study revealed that adsorption process is exothermic, energetically favorable and resulting in the decrease in randomness. Chemisorption is found to be the dominant mechanism as confirmed by pH effect, Langmuir isotherm, PSO kinetics, IPD model, and thermodynamics parameters. PSA beads were successfully regenerated using ethanol in a course of 120 min and re-used for five times. To sum up, the PSA adsorbent's impressive adsorption capability of 1666.66 mg/g highlights its potential as a successful solution for methylene blue removal. The results of this study add to the expanding corpus of information on sophisticated adsorption materials and demonstrate PSA's potential for real-world uses in wastewater treatment and environmental clean-up.
PubMed: 38955975
DOI: 10.1007/s11356-024-33573-7 -
The AAPS Journal Jul 2024The paper highlights the necessity for a robust regulatory framework for assessing nanomedicines and their off-patent counterparts, termed as nanosimilar, which could be... (Review)
Review
The paper highlights the necessity for a robust regulatory framework for assessing nanomedicines and their off-patent counterparts, termed as nanosimilar, which could be considered as 'similar' to the prototype nanomedicine,based on essential criteria describing the 'similarity'. The term 'similarity' should be focused on criteria that describe nanocarriers, encompassing their physicochemical, thermodynamic, morphological, and biological properties, including surface interactions and pharmacokinetics. Nanocarriers can be regarded as advanced self-assembled excipients (ASAEs) due to their complexity and chaotic behavior and should be evaluated by using essential criteria in order for off-patent nanomedicines be termed as nanosimilars, from a regulatory perspective. Collaboration between the pharmaceutical industry, regulatory bodies, and artificial intelligence (AI) startups is pivotal for the precise characterization and approval processes for nanomedicines and nanosimilars and embracing innovative tools and terminology facilitates the development of a sustainable regulatory framework, ensuring safety and efficacy. This crucial shift toward precision R&D practices addresses the complexity inherent in nanocarriers, paving the way for therapeutic advancements with economic benefits.
Topics: Nanomedicine; Humans; Biosimilar Pharmaceuticals; Artificial Intelligence; Nanoparticles; Drug Industry; Drug Approval; Drug Carriers
PubMed: 38955936
DOI: 10.1208/s12248-024-00942-6 -
The AAPS Journal Jul 2024The selection of skin is crucial for the in vitro permeation test (IVPT). The purpose of this study was to investigate the influence of different freezing-thawing...
The selection of skin is crucial for the in vitro permeation test (IVPT). The purpose of this study was to investigate the influence of different freezing-thawing processes on the barrier function of skin and the transdermal permeability of granisetron and lidocaine. Rat and hairless mouse skins were thawed at three different conditions after being frozen at -20℃ for 9 days: thawed at 4℃, room temperature (RT), and 32℃. There were no significant differences in the steady-state fluxes of drugs between fresh and thawed samples, but compared with fresh skin there were significant differences in lag time for the permeation of granisetron in rat skins thawed at RT and 32℃. Histological research and scanning electron microscopy images showed no obvious structural damage on frozen/thawed skin, while immunohistochemical staining and enzyme-linked immunosorbent assay for the tight junction (TJ) protein Cldn-1 showed significantly impaired epidermal barrier. It was concluded that the freezing-thawing process increases the diffusion rate of hydrophilic drugs partly due to the functional degradation of TJs. It's recommended that hairless, inbred strains and identical animal donors should be used, and the selected thawing method of skin should be validated prior to IVPT, especially for hydrophilic drugs.
Topics: Animals; Freezing; Skin; Mice; Mice, Hairless; Skin Absorption; Rats; Permeability; Male; Administration, Cutaneous; Lidocaine; Rats, Sprague-Dawley
PubMed: 38955873
DOI: 10.1208/s12248-024-00941-7 -
Journal of Cancer Research and Clinical... Jul 2024To explore the effect and mechanism of relaxin (RLX) in the growth and metastasis of livercancer after combination treatment with transarterial chemoembolization (TACE).
OBJECTIVE
To explore the effect and mechanism of relaxin (RLX) in the growth and metastasis of livercancer after combination treatment with transarterial chemoembolization (TACE).
MATERIALS AND METHODS
HCCLM3 and Huh-7 cells were adopted to evaluate the effect of tumor proliferation, migration, and invasion after RLX administration in vitro. The rabbit VX2 model was used to evaluate the biosafety, doxorubicin penetration, local tumor response, tumor metastasis, and survival benefit of RLX combined with TACE treatment.
RESULTS
RLX did not affect the proliferation, migration, or invasion of HCCLM3 and Huh-7 cells, and the expression of E-cadherin and HIF-1α also remained unchanged while the MMP-9 protein was upregulated in vitro. In the rabbit VX2 model, compared to the normal saline group (NS), RLX group (RLX) and TACE mono-therapy group (TACE), the group that received TACE combined with RLX (TACE + RLX) showed an improved local tumor response and survival benefit. Furthermore, TACE combined with RLX was found to reduce tumor metastasis. This combination therapy reduced the fibrotic extracellular matrix in the tumor microenvironment, allowing for better penetration of doxorubicin, improved infiltration of CD8+ T cells and affected the secretion of cytokines. Additionally, RLX combined with TACE was able to decrease the expression of HIF-1α and PD-L1. The biosafety of TACE combined with RLX was also confirmed.
CONCLUSION
RLX synergized with TACE by mitigating the fibrotic extracellular matrix and tumor hypoxic microenvironment, improving the therapeutic effect and inhibiting metastasis during the treatment of liver cancer.
Topics: Animals; Chemoembolization, Therapeutic; Rabbits; Relaxin; Liver Neoplasms; Doxorubicin; Humans; Combined Modality Therapy; Cell Proliferation; Cell Line, Tumor; Disease Models, Animal; Carcinoma, Hepatocellular; Neoplasm Metastasis
PubMed: 38955827
DOI: 10.1007/s00432-024-05864-6 -
Supportive Care in Cancer : Official... Jul 2024The study investigates cryotherapy's efficacy in mitigating Chemotherapy-induced peripheral neuropathy (CIPN), an adverse effect of chemotherapy that often leads to... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The study investigates cryotherapy's efficacy in mitigating Chemotherapy-induced peripheral neuropathy (CIPN), an adverse effect of chemotherapy that often leads to dosage reduction or treatment discontinuation.
METHOD
The study was registered with PROSPERO (CRD42023428936). A literature search was conducted using the PubMed, Embase, and Cochrane Library databases. Randomized and nonrandomized controlled trials that investigated the effects of cryotherapy on CIPN were included for systematic review and meta-analysis. The primary outcome for prevention was the incidence of CIPN.
RESULTS
We identified 17 trials involving 2,851 patients. In total, 11 trials compared the incidence of CIPN between cryotherapy and control groups. Significant differences in the incidence of CIPN at the midpoint and end of chemotherapy were observed, with risk ratios (RRs) of 0.23 (95% confidence interval [CI] = 0.13 to 0.43) and 0.54 (95% CI = 0.33 to 0.88), respectively. Cryotherapy also significantly reduced the incidence of sensory CIPN, with an RR of 0.67 (95% CI = 0.49 to 0.92). Additionally, cryotherapy demonstrated a significant reduction in the incidence of CIPN in patients with gynecological cancers (RR = 0.24, 95% CI = 0.14 to 0.41). Significantly favorable global quality of life scores following chemotherapy (standardized mean difference = 1.43; 95% CI = 0.50 to 2.36) and relieved neuropathic symptoms were found with cryotherapy.
CONCLUSIONS
Cryotherapy demonstrates a pronounced preventive effect against the development of CIPN, providing substantial symptomatic relief and quality of life improvements for patients undergoing chemotherapy. The administration of cryotherapy through the use of frozen gloves and socks, or continuous-flow cooling systems, optimally initiated 15 min prior to and concluded 15 min following chemotherapy, is recommended for achieving maximum therapeutic efficacy.
Topics: Humans; Peripheral Nervous System Diseases; Cryotherapy; Antineoplastic Agents; Randomized Controlled Trials as Topic; Incidence; Neoplasms
PubMed: 38955817
DOI: 10.1007/s00520-024-08680-3 -
Zhonghua Er Ke Za Zhi = Chinese Journal... Jul 2024To evaluate the effectiveness and safety of treatment with Burosumab in pediatric X-linked hypophosphatemia (XLH) patients. In this retrospective case study, 4...
To evaluate the effectiveness and safety of treatment with Burosumab in pediatric X-linked hypophosphatemia (XLH) patients. In this retrospective case study, 4 children with pediatric XLH, who were treated with Burosumab in Beijing Children's Hospital, Capital Medical University and Shandong Provincial Hospital affiliated to Shandong First Medical University from July 2022 to December 2023, were selected as the study objects. We collected and analyzed their clinical characteristics, biochemical indicators, imaging results, and treatment. The children were followed up every 3 months until December 2023, and the clinical outcomes and adverse drug reactions after treatment were evaluated. Of the 4 patients, 3 were males and 1 was female; they were aged 6.7, 2.9, 2.1, and 2.3 years, respectively. Three patients had previously received treatment with phosphate supplements and active vitamins, but their wadding gait and lower limb deformities did not improve significantly, neither did their imaging changes of active richets. The initial dose of Burosumab in the 4 patients was 0.8 mg/kg, administered subcutaneously every 2 weeks, with a treatment course of 0.8-1.3 years. The fasting serum phosphorus and tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) of the 4 patients before treatment were 0.72, 0.95, 0.81, 0.66 mmol/L and 0.67, 0.85, 0.87, 0.61 mmol/L, respectively. At the last follow-up, the fasting serum phosphorus and TmP/GFR levels were significantly increased (0.96, 1.09, 1.09, 0.90 mmol/L, and 0.85, 0.79, 1.03, 0.98 mmol/L, respectively). Among them, only the TmP/GFR level (1.17 mmol/L) in case 2 achieved normal values at 3 months post-therapy, while the rest did not reach the normal range for children of the same age. After treatment, the alkaline phosphatase levels of all patients gradually decreased (the values were 461, 240, 423, and 237 U/L, respectively), and the ALP levels in cases 2 and 4 returned to normal at the last visit. Case 4 showed a slight increase in parathyroid hormone (PTH) levels after 9 months of treatment, while the PTH levels in the rest 3 cases remained normal. Case 1 underwent a 6-minute walking test, and the walking distance increased from 245 m to 570 m. Abnormal gait, lower limb deformity, and the severity of rickets in the 4 patients had all improved. No adverse drug reactions such as nephrocalcinosis, local skin injection reaction, hyperphosphatemia, or vitamin D deficiency were observed. Burosumab can improve clinical symptoms in children with XLH with a good safety profile.
Topics: Humans; Male; Female; Familial Hypophosphatemic Rickets; Antibodies, Monoclonal, Humanized; Child; Retrospective Studies; Child, Preschool; Treatment Outcome
PubMed: 38955688
DOI: 10.3760/cma.j.cn112140-20231201-00404 -
The Primary Care Companion For CNS... Jun 2024
Topics: Humans; Stress Disorders, Post-Traumatic; Prazosin; Male; Psychological Distress; Adult; Middle Aged; Adrenergic alpha-1 Receptor Antagonists; Female
PubMed: 38954793
DOI: 10.4088/PCC.23cr03696 -
PloS One 2024This study aimed to evaluate the effect of antimicrobial photodynamic therapy (aPDT) and the use of probiotics on the treatment of halitosis. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study aimed to evaluate the effect of antimicrobial photodynamic therapy (aPDT) and the use of probiotics on the treatment of halitosis.
METHODS
Fifty-two participants, aged from 18 to 25 years, exhaling sulfhydride (H2S) ≥ 112 ppb were selected. They were allocated into 4 groups (n = 13): Group 1: tongue scraper; Group 2: treated once with aPDT; Group 3: probiotic capsule containing Lactobacillus salivarius WB21 (6.7 x 108 CFU) and xylitol (280mg), 3 times a day after meals, for 14 days; Group 4: treated once with aPDT and with the probiotic capsule for 14 days. Halimetry with gas chromatography (clinical evaluation) and microbiological samples were collected from the dorsum of the tongue before and after aPDT, as well as after 7, 14, and 30 days. The clinical data failed to follow a normal distribution; therefore, comparisons were made using the Kruskal-Wallis test (independent measures) and Friedman ANOVA (dependent measures) followed by appropriate posthoc tests, when necessary. For the microbiological data, seeing as the data failed to follow a normal distribution, the Kruskal-Wallis rank sum test was performed with Dunn's post-test. The significance level was α = 0.05.
RESULTS
Clinical results (halimetry) showed an immediate significant reduction in halitosis with aPDT (p = 0.0008) and/or tongue scraper (p = 0.0006). Probiotics showed no difference in relation to the initial levels (p = 0.7530). No significant differences were found in the control appointments. The amount of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola were not altered throughout the analysis (p = 0.1616, p = 0.2829 and p = 0.2882, respectively).
CONCLUSION
There was an immediate clinical reduction of halitosis with aPDT and tongue scraping, but there was no reduction in the number of bacteria throughout the study, or differences in the control times, both in the clinical and microbiological results. New clinical trials are necessary to better assess the tested therapies.
TRIAL REGISTRATION
Clinical Trials NCT03996044.
Topics: Humans; Halitosis; Probiotics; Adult; Photochemotherapy; Male; Female; Adolescent; Young Adult; Ligilactobacillus salivarius; Tongue; Anti-Infective Agents
PubMed: 38954692
DOI: 10.1371/journal.pone.0297351 -
PloS One 2024Sedatives are commonly used to promote sleep in intensive care unit patients. However, it is not clear whether sedation-induced states are similar to the biological...
Do all sedatives promote biological sleep electroencephalogram patterns? A machine learning framework to identify biological sleep promoting sedatives using electroencephalogram.
BACKGROUND
Sedatives are commonly used to promote sleep in intensive care unit patients. However, it is not clear whether sedation-induced states are similar to the biological sleep. We explored if sedative-induced states resemble biological sleep using multichannel electroencephalogram (EEG) recordings.
METHODS
Multichannel EEG datasets from two different sources were used in this study: (1) sedation dataset consisting of 102 healthy volunteers receiving propofol (N = 36), sevoflurane (N = 36), or dexmedetomidine (N = 30), and (2) publicly available sleep EEG dataset (N = 994). Forty-four quantitative time, frequency and entropy features were extracted from EEG recordings and were used to train the machine learning algorithms on sleep dataset to predict sleep stages in the sedation dataset. The predicted sleep states were then compared with the Modified Observer's Assessment of Alertness/ Sedation (MOAA/S) scores.
RESULTS
The performance of the model was poor (AUC = 0.55-0.58) in differentiating sleep stages during propofol and sevoflurane sedation. In the case of dexmedetomidine, the AUC of the model increased in a sedation-dependent manner with NREM stages 2 and 3 highly correlating with deep sedation state reaching an AUC of 0.80.
CONCLUSIONS
We addressed an important clinical question to identify biological sleep promoting sedatives using EEG signals. We demonstrate that propofol and sevoflurane do not promote EEG patterns resembling natural sleep while dexmedetomidine promotes states resembling NREM stages 2 and 3 sleep, based on current sleep staging standards.
Topics: Humans; Electroencephalography; Machine Learning; Hypnotics and Sedatives; Male; Adult; Female; Sleep; Propofol; Sevoflurane; Dexmedetomidine; Sleep Stages; Young Adult
PubMed: 38954679
DOI: 10.1371/journal.pone.0304413