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European Journal of Pharmaceutical... Jun 2024Tacrolimus (FK506) is a cornerstone of GVHD-prophylaxis treatment in paediatrics undergoing haematopoietic stem cell transplantation (HSCT). However, due to concerns...
Tacrolimus (FK506) is a cornerstone of GVHD-prophylaxis treatment in paediatrics undergoing haematopoietic stem cell transplantation (HSCT). However, due to concerns about highly inter/intra-individual variability, precision dosing of FK506 is crucial. Cytochrome P450(CYP) 3A4 and 3A5 are considered important sources of FK506 pharmacokinetic variability. Nevertheless, the impact of age-related maturation in hepatic and intestinal CYP3A4/3A5 enzymes remains unknown in paediatric HSCT patients. Physiologically-based pharmacokinetic (PBPK) models were developed and verified in adult volunteers and adult HSCT patients using GastroPlus (version 9.0), and then extrapolated to paediatric HSCT patients, taking into account the maturation of CYP3A4 and CYP3A5. Default CYP3A4 and CYP3A5 ontogeny profiles were updated based on the latest reports. The paediatric PBPK model was evaluated with independent data collected from Sun Yat-sen Memorial Hospital (86 paediatric HSCT patients, 1 to 16 -year-old). Simulations were performed to evaluate a reported FK506 dosing regimen in infants and children with different CYP3A5 genotypes. Extensive PBPK model validation indicated good predictability, with the predicted/observed (P/O) ratios within the range of 0.80-fold to 1.25-fold. Blood tacrolimus concentration-time curves were comparable between the real and virtual patients. Simulations showed that the higher levels of tacrolimus in 9-month-old to 3-year-old infants were mainly attributed to the CYP3A4/3A5 ontogeny profiles, which resulted in lower clearance and higher exposure relative to dose. The oral dosage of 0.1 mg/kg/day (q12 h) is considered appropriate for paediatric HSCT patients 9 months to 15 years of age with CYP3A5 *1/*1 genotypes. Lower doses were required for paediatric HSCT patients with CYP3A5 *1/*3 (0.08 mg/kg/day, q12h) or CYP3A5 *3/*3 genotypes (0.07 mg/kg/day, q12h), and analyses demonstrated 12.5%-20% decreases in ≤3-year-old patients. The study highlights the feasibility of PBPK modelling to explore age-related enzyme maturation in infants and children(≤3-year-old) undergoing HSCT and emphasizes the need to include hepatic and gut CYP3A4/3A5 maturation parameters.
PubMed: 38906231
DOI: 10.1016/j.ejps.2024.106839 -
Ecotoxicology and Environmental Safety Jun 2024Exposure to light at night (LAN) has been associated with multiple adverse health outcomes. However, evidence is limited regarding the impacts of LAN exposure on human...
BACKGROUND
Exposure to light at night (LAN) has been associated with multiple adverse health outcomes. However, evidence is limited regarding the impacts of LAN exposure on human inflammation.
OBJECTIVES
To examine the association between real-ambient bedroom LAN exposure with systemic inflammation and circadian rhythm of inflammatory markers.
METHODS
Using data from a prospective cohort study of Chinese young adults. At baseline, bedroom LAN exposure was measured with a portable illuminance meter; fasting blood sample for high-sensitivity C-reactive protein (hs-CRP) assay was collected. At 3-year follow-up, 20 healthy young adults (10 LAN < 5 lx, 10 LAN ≥ 5 lx) were recruited from the same cohort; time-series venous blood samples were sampled every 4 h over a 24 h-cycle for the detection of 8 inflammatory markers. Circadian rhythm of inflammatory markers was assessed using cosinor analysis.
RESULTS
At baseline, the average age of the 276 participants was 18.7 years, and 33.3 % were male. Higher levels of bedroom LAN exposure were significantly associated with increased hs-CRP levels. The association between bedroom LAN exposure and systemic inflammation was only significant in the inactive group (MVPA < 2 h/d) but not in the physically active group (MVPA ≥ 2 h/d). In addition, exposure to higher levels of nighttime light (LAN ≥ 5 lx) disrupted circadian rhythms (including rhythmic expression, circadian amplitude and circadian phase) of some inflammatory cytokines and inflammatory balance indicators.
CONCLUSION
Exposure to bedroom nighttime light increases systemic inflammation and disrupts circadian rhythm of inflammatory markers. Keep bedroom darkness at night may represent important strategies for the prevention of chronic inflammation. Additionally, for people living a community with higher nighttime light pollution, regular physical activity may be a viable option to counteract the negative impacts of LAN exposure on chronic inflammation.
PubMed: 38905938
DOI: 10.1016/j.ecoenv.2024.116590 -
Waste Management (New York, N.Y.) Jun 2024Tetracycline is an antibiotic with extensive veterinary use in the livestock industry. However, their widespread application poses risks to soil health as residue in...
Tetracycline is an antibiotic with extensive veterinary use in the livestock industry. However, their widespread application poses risks to soil health as residue in livestock feces, and their removal is crucial for sustainable soil-ecosystem development. Physical and chemical approaches to extract tetracycline may have adverse effects on soil ecosystems, but no studies have thus far examined the potential for biological methods, such as collective degradation action of soil fauna. Thus, this study aimed to investigate the synergistic effects of lactic acid bacteria (LAB) and earthworms (Eisenia fetida) on biodegradation of tetracycline residues in sheep manure. We assessed earthworm biomass, tetracycline residue, and bacterial communities in both earthworm intestines and vermicompost. Earthworm biomass and tetracycline degradation efficiency increased significantly with LAB addition, with a degradation rate of up to 80.16%. This increase may be attributable to LAB acting as electron donors to spur tetracycline degradation. Additionally, we noted that tetracycline presence significantly influenced bacterial communities in earthworm intestines and vermicompost, elevating the abundance of potential pathogenic bacteria (e.g., Flavobacterium, Gammaproteobacteria, and Enterobacteriaceae). This finding suggests that heightened environmental stress from antibiotics could actually facilitate the growth of less prevalent bacteria, including potential pathogens. In conclusion, our study provides evidence supporting the effectiveness of LAB and earthworms in degrading tetracycline residues. In particular, LAB appears to mitigate stress from tetracycline exposure in earthworms, thus increasing their vermicomposting efficacy. Our work has important implications for soil management, with the potential to enhance pollution clean-up rates while minimizing negative side-effects to soil microbial communities.
PubMed: 38905906
DOI: 10.1016/j.wasman.2024.06.007 -
Frontiers in Endocrinology 2024To characterize the influence of female-specific hormones on women's thyroid function, the study investigated the influence of extra progestin from oral contraceptives...
INTRODUCTION
To characterize the influence of female-specific hormones on women's thyroid function, the study investigated the influence of extra progestin from oral contraceptives on inducing thyroid dysfunction.
METHODS
Sixty female Wistar rats were divided into six groups based on levonorgestrel or desogestrel administration as the main active agents: control, low (0.0039 mg*20-fold), medium (0.0039 mg*100-fold), high (0.0318 mg*100-fold) levonorgestrel (pure product); and low (0.0083 mg*20-fold) and high (0.0083 mg*100-fold) desogestrel (pure product). Progestin was administered by gavage every 4 days for 1 month. Statistical analysis was performed using one-way analysis of variance and the Kruskal-Wallis test.
RESULTS
Following levonorgestrel gavage, serum free T and thyroidstimulating hormone levels were significantly lower in the experimental group than that in the control group (=0.013 and 0.043). After desogestrel gavage, the serum free T and free T levels were lower in the experimental group than that in the control group (=0.019 and 0.030). Thyroid hormone antibody concentrations were lower in rats administered levonorgestrel and desogestrel than that in control rats. Moreover, exposure to progestin upregulated the expression of the thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid.
DISCUSSION
Progestin stimulation enhanced the proliferation of follicular epithelial cells in rat thyroid tissues. Progestin exposure could cause thyroid dysfunction by upregulating the transcription of thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid, thus inducing pathomorphological changes in rats' thyroid.
Topics: Animals; Female; Rats, Wistar; Rats; Progestins; Thyroid Gland; Levonorgestrel; Desogestrel; Thyroxine; Thyroid Hormones; Thyroid Function Tests
PubMed: 38904035
DOI: 10.3389/fendo.2024.1362774 -
Frontiers in Pharmacology 2024Tacrolimus (Tac) is commonly used for postoperative immunosuppressive therapy in transplant patients. However, problems, for example, low bioavailability and unstable...
BACKGROUND
Tacrolimus (Tac) is commonly used for postoperative immunosuppressive therapy in transplant patients. However, problems, for example, low bioavailability and unstable plasma concentration, persist for a long time, Studies have reported that the deoxyschizandrin could effectively improve these problems, but the pharmacokinetic parameters (PKs) of Tac combined with deoxyschizandrin are still unknown.
METHOD
In this study, an UHPLC-MS/MS method has been established for simultaneous quantitation of Tac and deoxyschizandrin. The PKs of Tac influenced by different doses of deoxyschizandrin after single and multiple administrations were analyzed, and the different impact of deoxyschizandrin and Wuzhi capsule on PKs of Tac were compared.
RESULT
The modified UHPLC-MS/MS method could rapid quantification of Tac and deoxyschizandrin within 2 min using bifendatatum as the internal standard (IS). All items were successfully validated. The of deoxyschizandrin increased from 148.27 ± 23.20 to 229.13 ± 54.77 ng/mL in rats after multiple administrations for 12 days. After co-administration of 150 mg/mL deoxyschizandrin, Tac had an earlier and greater and AUC, and the and AUC of Tac increased from 14.26 ± 4.73 to 54.48 ± 14.37 ng/mL and from 95.10 ± 32.61 to 315.23 ± 92.22 h/ng/mL, respectively; this relationship was positively proportional to the dosage of deoxyschizandrin. In addition, compared with Wuzhi capsule, the same dose of deoxyschizandrin has a better effective on Tac along with more stable overall PKs.
CONCLUSION
An UHPLC-MS/MS method was established and validated for simultaneous detection of deoxyschizandrin and Tac. Deoxyschizandrin could improve the exposure level and stability of Tac, besides, this effect is better than Wuzhi capsule in same dose.
PubMed: 38903992
DOI: 10.3389/fphar.2024.1344369 -
Frontiers in Pharmacology 2024Diabetic nephropathy (DN) is known as the most common complication of diabetes, resulting from a complex inheritance-environment interaction without effective clinical...
Diabetic nephropathy (DN) is known as the most common complication of diabetes, resulting from a complex inheritance-environment interaction without effective clinical treatments. Herein, we revealed the protective effects and mechanisms of Zn(II)-curcumin, a curcumin derivative, against streptozotocin-induced DN in rats in the presence or absence of cadmium exposure. The present study focused on investigating the therapy of Zn(II)-curcumin against cadmium-aggravated DN by regulating gut microbiota, metabolism, inflammation and zinc homeostasis based on pathological changes, TLR4/NF-κB signaling pathway, inductively coupled plasma-mass spectrometry (ICP-MS), 16S rRNA gene sequencing and gas chromatography-mass spectrometer (GC-MS). We found Zn(II)-curcumin significantly mitigated the cadmium-aggravated phenotypes of diabetic nephropathy, as indicated by the remission of renal dysfunction, pathological changes, inflammation and zinc dyshomeostasis in streptozotocin-treated rats exposed to cadmium. Administration of Zn(II)-curcumin significantly alleviated the dysbiosis of gut microbiota and the changes of serum metabolite profiles in rats treated with streptozotocin in combination with cadmium. Notably, fecal microbial transplantation identified the ability of Zn(II)-curcumin to regulate renal function, inflammation and zinc homeostasis was partly dependent on the gut microbiota. These findings revealed that Zn(II)-curcumin alleviated cadmium-aggravated diabetic nephropathy by reshaping the gut microbiota and zinc homeostasis, which provided unique insights into the mechanisms of the treatment and prevention of diabetic nephropathy.
PubMed: 38903987
DOI: 10.3389/fphar.2024.1411230 -
RSC Advances Jun 2024In recent decades, environmental protection and energy issues have gained significant attention, and the development of efficient, environmentally friendly catalysts has...
In recent decades, environmental protection and energy issues have gained significant attention, and the development of efficient, environmentally friendly catalysts has become especially crucial for the advancement of photocatalytic technology. This study employs the sintering method to produce biochar. A hybrid photocatalyst for the degradation of RHB under visible light was prepared by loading varying proportions of biochar onto g-CN using ultrasonic technology. Among them, 2% CGCD (2% biochar/g-CN) achieved a degradation rate of 91.3% for RHB after 30 minutes of visible light exposure, which was more than 25% higher than GCD (g-CN), and exhibited a higher photocurrent intensity and lower impedance value. The enhancement in photocatalytic activity is primarily attributed to the increased utilization efficiency of visible light and the electron transfer channel effect from a minor amount of biochar, effectively reducing the recombination of photo-generated charge carriers on the g-CN surface, thereby significantly improving photocatalytic activity. The degradation of RHB is synergistically mediated by O , h (photo-generated holes), and ˙OH. The free radical capture experiment indicates that O and ˙OH are the primary active components, followed by h.
PubMed: 38903670
DOI: 10.1039/d4ra03232b -
Communications Biology Jun 2024Dietary emulsifiers are linked to various diseases. The recent discovery of the role of gut microbiota-host interactions on health and disease warrants the safety...
Dietary emulsifiers are linked to various diseases. The recent discovery of the role of gut microbiota-host interactions on health and disease warrants the safety reassessment of dietary emulsifiers through the lens of gut microbiota. Lecithin, sucrose fatty acid esters, carboxymethylcellulose (CMC), and mono- and diglycerides (MDG) emulsifiers are common dietary emulsifiers with high exposure levels in the population. This study demonstrates that sucrose fatty acid esters and carboxymethylcellulose induce hyperglycemia and hyperinsulinemia in a mouse model. Lecithin, sucrose fatty acid esters, and CMC disrupt glucose homeostasis in the in vitro insulin-resistance model. MDG impairs circulating lipid and glucose metabolism. All emulsifiers change the intestinal microbiota diversity and induce gut microbiota dysbiosis. Lecithin, sucrose fatty acid esters, and CMC do not impact mucus-bacterial interactions, whereas MDG tends to cause bacterial encroachment into the inner mucus layer and enhance inflammation potential by raising circulating lipopolysaccharide. Our findings demonstrate the safety concerns associated with using dietary emulsifiers, suggesting that they could lead to metabolic syndromes.
Topics: Animals; Emulsifying Agents; Dysbiosis; Gastrointestinal Microbiome; Mice; Male; Metabolic Diseases; Mice, Inbred C57BL; Carboxymethylcellulose Sodium; Sucrose; Insulin Resistance; Lecithins
PubMed: 38902371
DOI: 10.1038/s42003-024-06224-3 -
World Journal of Clinical Cases Jun 2024Photoaging, a result of chronic sun exposure, leads to skin damage and pigmentation changes. Traditional treatments may have limitations in high-altitude areas like...
BACKGROUND
Photoaging, a result of chronic sun exposure, leads to skin damage and pigmentation changes. Traditional treatments may have limitations in high-altitude areas like Yunnan Province. Intradermal Col Ι injections stimulate collagen production, potentially improving skin quality. This study aims to assess the efficacy and safety of this treatment for photoaging.
AIM
To evaluate the efficacy and safety of intradermal type Ι collagen (Col Ι) injection for treating photoaging.
METHODS
This prospective, self-controlled study investigated the impact of intradermal injections of Col Ι on skin photodamage in 20 patients from the Yunnan Province. Total six treatment sessions were conducted every 4 wk ± 3 d. Before and after each treatment, facial skin characteristics were quantified using a VISIA skin detector. Skin thickness data were assessed using the ultrasound probes of the Dermalab skin detector. The Face-Q scale was used for subjective evaluation of the treatment effect by the patients.
RESULTS
The skin thickness of the right cheek consistently increased after each treatment session compared with baseline. The skin thickness of the left cheek significantly increased after the third through sixth treatment sessions compared with baseline. The skin thickness of the right zygomatic region increased after the second to sixth treatment sessions, whereas that of the left zygomatic region showed a significant increase after the fourth through sixth treatment sessions. The skin thickness of both temporal regions significantly increased after the fifth and sixth treatment sessions compared with baseline ( < 0.05). These findings were also supported by skin ultrasound images. The feature count for the red areas and wrinkle feature count decreased following the treatment ( < 0.05). VISIA assessments also revealed a decrease in the red areas after treatment. The Face-Q-Satisfaction with Facial Appearance Overall and Face-Q-Satisfaction with Skin scores significantly increased after each treatment session. The overall appearance of the patients improved after treatment.
CONCLUSION
Intradermal Col Ι injection improves photoaging, with higher patient satisfaction and fewer adverse reactions, and could be an effective treatment method for populations residing in high-altitude areas.
PubMed: 38899303
DOI: 10.12998/wjcc.v12.i16.2713 -
Journal of Global Health Jun 2024There is increasing evidence on the link between environmental factors and myopia in children and adolescents, yet with inconsistent conclusions. We investigated the...
BACKGROUND
There is increasing evidence on the link between environmental factors and myopia in children and adolescents, yet with inconsistent conclusions. We investigated the associations between socioeconomic inequalities and green space with myopia in school-aged students participating in the Tianjin Child and Adolescent Research of Eye (TCARE) study.
METHODS
We obtained data from a population-based dynamic cohort study conducted in Tianjin, China, in 2021 and followed up in 2022. We included 1 245 271 participants from 16 districts with an average age of 11.6 years (standard deviation = 3.3) in our analysis. We synthesized their area-level SES through a prediction model that combined economic, educational, and health care variables and assessed the greenness levels surrounding the school using the Normalized Difference Vegetation Index (NDVI) based on data obtained through satellite remote sensing. We performed generalised linear mixed effects analyses for each myopia outcome separately, with adjustments for students' sex, years of education completed, and the school's geographical location.
RESULTS
We observed that students living in low SES areas had the highest prevalence of myopia (60.7%) in the last screening in 2022, as well as a higher incidence of one-year myopia (26.4%) compared to those residing in middle SES areas (22.7%). With a 0.1 increase in the 250, 500, and 1000 m buffer NDVI, the prevalence of myopia dropped by 6.3% (odds ratio (OR) = 0.937; 95% confidence interval (CI) = 0.915, 0.960), 7.7% (OR = 0.923; 95% CI = 0.900, 0.946), and 8.7% (OR = 0.913; 95% CI = 0.889, 0.937), respectively. The interaction analysis showed that low SES and low greenness exacerbate the prevalence of myopia. Findings from longitudinal analyses consistently demonstrated a correlation between higher values of NDVI and a slower progression of myopia. These findings remained robust across sensitivity analyses, including for variables on parental myopia and students' behaviors.
CONCLUSIONS
Exposure to green spaces could play a crucial role in slowing the progression of myopia among school-aged students. Myopia control policies should prioritise young populations residing in low SES areas with limited access to green spaces, as they face the highest potential risks.
Topics: Humans; Myopia; Female; Male; China; Child; Adolescent; Cohort Studies; Students; Socioeconomic Factors; Prevalence; Parks, Recreational; Socioeconomic Disparities in Health; East Asian People
PubMed: 38898796
DOI: 10.7189/jogh.14.04140