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1.
Neural Regen Res ; 20(5): 1467-1482, 2025 May 01.
Article in English | MEDLINE | ID: mdl-39075913

ABSTRACT

JOURNAL/nrgr/04.03/01300535-202505000-00029/figure1/v/2024-07-28T173839Z/r/image-tiff Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties. A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury. A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity, and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar, thus limiting axonal reentry into the host spinal cord. Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury. We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders, Schwann cells migrated for considerable distances in both rostral and caudal directions. Such Schwann cell migration led to enhanced axonal regrowth, including the serotonergic and dopaminergic axons originating from supraspinal regions, and promoted recovery of locomotor and urinary bladder functions. Importantly, the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury, even when treatment was delayed for 3 months to mimic chronic spinal cord injury. These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

2.
Article in English | MEDLINE | ID: mdl-39312688

ABSTRACT

Chromatin organization is important for gene transcription in pig genome. However, its three-dimensional (3D) structure and dynamics are much less investigated than those in human. Here we applied the long-reads chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) method to map the whole-genome chromatin interactions mediated by CCCTC-binding factor (CTCF) and RNA polymerase Ⅱ (RNAPⅡ or POLⅡ) in porcine macrophage cells before and after polyinosinic-polycytidylic acid [Poly(I:C)] induction. Our results revealed that Poly(I:C) induction impacts the 3D genome organization in the 3D4/21 cells at the fine-scale chromatin loop level rather than at the large-scale domain level. Furthermore, our findings underscored the pivotal role of CTCF anchored chromatin interactions in reshaping chromatin architecture during immune responses. Knock-out of the CTCF locus further confirmed that the CTCF anchored enhancers are associated with the activation of immune genes via long-range interactions. Notably, ChIA-PET data also supported the spatial relationship between single nucleotide polymorphisms (SNPs) and the related gene transcription in 3D genome aspect. Our findings in this study provide new clues and potential targets to explore key elements related to diseases in swine and are also likely to shed light on elucidating chromatin organization and dynamics underlying the process of mammalian infectious diseases.

3.
Steroids ; : 109516, 2024 Sep 21.
Article in English | MEDLINE | ID: mdl-39313103

ABSTRACT

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of childbearing age. The role of Sprouty RTK Signaling Antagonist 4 (SPRY4) in ovarian function in PCOS was investigated herein focusing on its regulation of ERK1/2 phosphorylation. PCOS models were established in mice using dehydroepiandrosterone (DHEA). The expression levels of SPRY4 in ovarian tissues were analyzed through RT-qPCR and immunohistochemistry. SPRY4 knockdown was achieved via lentivirus, and its effects on endocrine function, ovarian morphology, oxidative stress, and ERK1/2 phosphorylation were evaluated. Afterwards, granulosa cells were isolated and treated with DHEA and ERK2 agonist tert-Butylhydroquinone. The impacts of ERK2 activation on the regulation of SPRY4 knockdown were assessed using ELISA, fluorescent probes, western blotting, and biochemical assays. SPRY4 knockdown normalized the estrous cycle, reduced serum levels of testosterone, anti-Müllerian hormone, and luteinizing hormone/follicle-stimulating hormone ratio, and improved ovarian morphology. Additionally, SPRY4 knockdown alleviated oxidative stress by decreasing reactive oxygen species and malondialdehyde levels while increasing superoxide dismutase activity. It also restored steroidogenic enzyme expression, which were disrupted by DHEA induction. In vitro, SPRY4 knockdown enhanced granulosa cell viability and reduced ERK1/2 phosphorylation, with tert-Butylhydroquinone reversing these effects and restoring oxidative stress and steroidogenesis disruptions. Together, SPRY4 modulates ERK1/2 phosphorylation to influence oxidative stress and steroidogenesis in PCOS. Targeting SPRY4 may provide novel therapeutic avenues for improving ovarian function and managing PCOS.

4.
Genes (Basel) ; 15(9)2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39336717

ABSTRACT

Heart failure (HF) is a significant health burden, with two major clinical subtypes: HF with reduced (HFrEF) and preserved ejection fraction (HFpEF). Blood pressure and lipid profile are established risk factors of HF. We performed univariable and multivariable Mendelian randomization (MR) analyses to assess potential causal effects of blood pressures and lipids on HF subtypes. Genetic instruments for blood pressures and lipids were derived from genome-wide association studies (GWASs) among the European participants of the UK Biobank. GWAS summaries of HFrEF and HFpEF were obtained from the meta-analysis of the European participants from the Million Veteran Program and the Vanderbilt University DNA Databank. Systolic blood pressure exhibited a supportive MR association primarily with HFpEF (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.04-1.23), while diastolic blood pressure had an independent MR association with HFrEF (OR, 1.43; 95% CI, 1.13-1.77). MR associations also supported the observation that higher levels of low-density lipoprotein cholesterol increase the risk for both subtypes (HFrEF OR, 1.10 and 95% CI, 1.05-1.17; HFpEF OR, 1.05 and 95% CI, 1.02-1.09). These findings underscore differences in HF subtype-specific risk profiles and mechanisms, which may lead to different interventional strategies for different HF subtypes.


Subject(s)
Blood Pressure , Genome-Wide Association Study , Heart Failure , Mendelian Randomization Analysis , Humans , Heart Failure/genetics , Blood Pressure/genetics , Male , Polymorphism, Single Nucleotide , Female , Lipids/blood , Lipids/genetics , Middle Aged , Stroke Volume/genetics , Cholesterol, LDL/blood , Cholesterol, LDL/genetics , Aged , Risk Factors
5.
Front Public Health ; 12: 1402191, 2024.
Article in English | MEDLINE | ID: mdl-39329003

ABSTRACT

Introduction: Household health expenditure plays a crucial role in the daily spending of individuals. Meanwhile, the attention of the public to subjective well-being (SWB) is constantly increasing in China. Household health expenditure could reduce real family income, harming personal SWB. However, the aim of household health expenditure is to improve the physical condition of an individual, and improvements in individual health could enhance personal SWB. Therefore, the effect of household health expenditure on personal SWB is uncertain; hence, it is essential to assess the effects of household health expenditure on the SWB of Chinese residents. Methods: The Chinese family panel studies database from 2016 to 2020 was applied in this study. A fixed effects model was used to examine the impact of household medical and health protection expenses on personal SWB. Fixed effects instrumental variable regression and propensity score matching were then used to conduct robustness testing. Results: On the basis of a fixed effects model, it was found that household medical and health protection expenditure did not improve the happiness and life satisfaction of individuals; rather, household health protection expenditure could significantly reduce personal happiness. Fixed effects instrumental variable regression and propensity score matching analysis supported these results. Household health protection expenditure had a greater negative impact on the happiness and life satisfaction of females compared with males. Conclusion: Household health expenditure does not improve the SWB of individuals in China; this has certain significance for the formulation of relevant policies.


Subject(s)
Family Characteristics , Health Expenditures , Personal Satisfaction , Humans , China , Health Expenditures/statistics & numerical data , Female , Male , Adult , Middle Aged , Happiness
6.
Sensors (Basel) ; 24(18)2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39338884

ABSTRACT

Direct detection of miRNA is currently limited by the complex amplification and reverse transcription processes of existing methods, leading to low sensitivity and high operational demands. Herein, we developed a CRISPR/Cas13a-mediated photoelectrochemical (PEC) biosensing platform for direct and sensitive detection of miRNA-21. The direct and specific recognition of target miRNA-21 by crRNA-21 eliminates the need for pre-amplification and reverse transcription of miRNA-21, thereby preventing signal distortion and enhancing the sensitivity and precision of target detection. When crRNA-21 binds to miRNA-21, it activates the trans-cleavage activity of CRISPR/Cas13a, leading to the non-specific cleavage of biotin-modified DNA with uracil bases (biotin-rU-DNA). This cleavage prevents the biotin-rU-DNA from being immobilized on the electrode surface. As a result, streptavidin cannot attach to the electrode via specific biotin binding, reducing spatial resistance and causing a positively correlated increase in the photocurrent response. This Cas-PEC biosensor has good analytical capabilities, linear responses between 10 fM and 10 nM, a minimum detection limit of 9 fM, and an excellent recovery rate in the analysis of real human serum samples. This work presented an innovative solution for detecting other biomarkers in bioanalysis and clinical diagnostics.


Subject(s)
Biosensing Techniques , CRISPR-Cas Systems , Electrochemical Techniques , MicroRNAs , Biosensing Techniques/methods , MicroRNAs/blood , MicroRNAs/analysis , MicroRNAs/genetics , Electrochemical Techniques/methods , Humans , Limit of Detection , Biotin/chemistry , DNA/chemistry , DNA/genetics , Electrodes
7.
Front Cardiovasc Med ; 11: 1445739, 2024.
Article in English | MEDLINE | ID: mdl-39238503

ABSTRACT

Protein Tyrosine Phosphatase 1B (PTP1B) has emerged as a significant regulator of metabolic and cardiovascular disease. It is a non-transmembrane protein tyrosine phosphatase that negatively regulates multiple signaling pathways integral to the regulation of growth, survival, and differentiation of cells, including leptin and insulin signaling, which are critical for development of obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. Given PTP1B's central role in glucose homeostasis, energy balance, and vascular function, targeted inhibition of PTP1B represents a promising strategy for treating these diseases. However, challenges, such as off-target effects, necessitate a focus on tissue-specific approaches, to maximize therapeutic benefits while minimizing adverse outcomes. In this review, we discuss molecular mechanisms by which PTP1B influences metabolic and cardiovascular functions, summarize the latest research on tissue-specific roles of PTP1B, and discuss the potential for PTP1B inhibitors as future therapeutic agents.

8.
Inorg Chem ; 63(38): 17351-17356, 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39240828

ABSTRACT

A new inorganic-organic hybrid polyoxoboroniobate {H4K2[Cu(cis-en)2(H2O)]9[Cu(cis-en)2]6[Cd2(cis-en)2(trans-en)][LiB2Nb29O86]2·79H2O} (1, en = ethylenediamine), is built from pagoda-shaped {LiB2Nb29O86} clusters, linear {Cd2(cis-en)2(trans-en)} bridging units, and copper-amine complexes. The {LiB2Nb29O86} cluster represents the first example of combining oxoboron clusters with polyoxoniobate clusters (PONbs). It consists of an unusual HPONb fragment {LiNb18O54}, a fused-ring structural boroniobate cluster {B2Nb5O13}, and a classical Lindqvist {Nb6O19} fragment. The {Cd2(cis-en)2(trans-en)} and [Cu(cis-en)2]2+ complexes link the pagoda-shaped {LiB2Nb29O86} clusters into 1D infinite ladder chains. This is the first instance of simultaneous coordination of the cis-en and trans-en ligands with a single metal cation in the inorganic-organic hybrid PONb family. Furthermore, 1 exhibits good proton conductivity.

9.
Aging Clin Exp Res ; 36(1): 186, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39254880

ABSTRACT

BACKGROUND: Disability is typically correlated with lower quality of life and decreased capacity for self-care. It has been demonstrated that multimorbidity is closely linked to a variety of unfavorable events, such as disability. Researchers are still figuring out how and to what extent co-morbidities impact disability, though. In order to fill up this gap, this study examines the prevalence and contributing variables of disability in older patients who have multimorbidity. METHODS: We conducted a systematic search of Pubmed, Cochrane Library, Web of Science, Embase, and CINAL databases for articles from their inception until September 2023. We selected co-morbid older adults aged > 60 years and used the ADL scale or any scale that assesses disability as an assessment tool. We excluded literature that did not meet the criteria, and literature that could not be included in the data we needed. We extracted data from the included literature and calculated synthetic prevalence rates, ORs, and 95% confidence intervals. RESULTS: A total of 32 papers (71,135 older adults) were included in the study. The prevalence of disability among older patients with multimorbidity was around 34.9% (95% CI = 25.8-43.9%). Subgroup analysis showed higher rates of disability among comorbidities who were older, female, unmarried, and long-term users of health services. And the incidence of disability increased each year. Meanwhile, the regions of the United States, China, and Spain showed higher rates of disability. CONCLUSIONS: Disability rates in older patients with multimorbidity are higher, thus it's critical to focus on risk factors while fully accounting for regional variances.


Subject(s)
Disabled Persons , Multimorbidity , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Activities of Daily Living , Disabled Persons/statistics & numerical data , Prevalence , Quality of Life
10.
Sensors (Basel) ; 24(17)2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39275468

ABSTRACT

Constructing a globally consistent high-precision map is essential for the application of mobile robots. Existing optimization-based mapping methods typically constrain robot states in pose space during the graph optimization process, without directly optimizing the structure of the scene, thereby causing the map to be inconsistent. To address the above issues, this paper presents a three-dimensional (3D) LiDAR mapping framework (i.e., BA-CLM) based on LiDAR bundle adjustment (LBA) cost factors. We propose a multivariate LBA cost factor, which is built from a multi-resolution voxel map, to uniformly constrain the robot poses within a submap. The framework proposed in this paper applies the LBA cost factors for both local and global map optimization. Experimental results on several public 3D LiDAR datasets and a self-collected 32-line LiDAR dataset demonstrate that the proposed method achieves accurate trajectory estimation and consistent mapping.

11.
Pestic Biochem Physiol ; 204: 106078, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39277391

ABSTRACT

Nilaparvata lugens is a notorious rice pest causing significant annual yield and economic losses. The use of entomopathogenic fungi offers a promising and eco-friendly approach to sustainable pest management programs. However, research in this area is currently limited to a few specific types of insects and other arthropods. This study aimed to analyze the biocontrol potential of Lecanicillium attenuatum against N. lugens. Bioassays showed that L. attenuatum 3166 induced >80% mortality in N. lugens following 7 d exposure. Greenhouse and field investigations demonstrated that L. attenuatum 3166 application leads to a substantial reduction in N. lugens populations. Under greenhouse conditions, fluorescence was detected in GFP-labeled L. attenuatum 3166 hyphae enveloping the bodies of N. lugens. In field trials, L. attenuatum 3166 treatment exhibited a control efficacy of up to 68.94% at 14 d post-application, which was comparable to that of the commercial entomopathogenic fungal agent. Genomic sequencing of L. attenuatum 3166 revealed a comprehensive array of genes implicated in its infestation and lethality. Further, the transcriptome sequencing analysis highlighted the elevated expression levels of genes encoding proteases, chitinases, cutinases, and phospholipases. Our findings highlight the potential of L. attenuatum 3166 as an effective biological control agent against N. lugens.


Subject(s)
Hemiptera , Hypocreales , Oryza , Pest Control, Biological , Animals , Oryza/parasitology , Oryza/microbiology , Pest Control, Biological/methods , Hemiptera/genetics , Hypocreales/genetics , Hypocreales/metabolism
12.
Nat Commun ; 15(1): 8040, 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39271663

ABSTRACT

The large mid-infrared (MIR) spectral region, ranging from 2.5 µm to 25 µm, has remained under-exploited in the electromagnetic spectrum, primarily due to the absence of viable transceiver technologies. Notably, the 8-14 µm long-wave infrared (LWIR) atmospheric transmission window is particularly suitable for free-space optical (FSO) communication, owing to its combination of low atmospheric propagation loss and relatively high resilience to turbulence and other atmospheric disturbances. Here, we demonstrate a direct modulation and direct detection LWIR FSO communication system at 9.1 µm wavelength based on unipolar quantum optoelectronic devices with a unprecedented net bitrate exceeding 55 Gbit s-1. A directly modulated distributed feedback quantum cascade laser (DFB-QCL) with high modulation efficiency and improved RF-design was used as a transmitter while two high speed detectors utilizing meta-materials to enhance their responsivity are employed as receivers; a quantum cascade detector (QCD) and a quantum-well infrared photodetector (QWIP). We investigate system tradeoffs and constraints, and indicate pathways forward for this technology beyond 100 Gbit s-1 communication.

13.
Molecules ; 29(17)2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39274957

ABSTRACT

Psoriasis, an immune-mediated inflammatory skin disorder, seriously affects the quality of life of nearly four percent of the world population. Euphorbia helioscopia L. is the monarch constituent of Chinese ZeQi powder preparation for psoriasis, so it is necessary to illustrate its active ingredients. Thus, twenty-three diterpenoids, including seven new ones, were isolated from the whole herb of E. helioscopia L. Compounds 1 and 2, each featuring a 2,3-dicarboxylic functionality, are the first examples in the ent-2,3-sceo-atisane or the ent-2,3-sceo-abietane family. Extensive spectroscopic analysis (1D, 2D NMR, and HRMS data) and computational methods were used to confirm their structures and absolute configurations. According to the previous study and NMR data from the jatropha diterpenes obtained in this study, some efficient 1H NMR spectroscopic rules for assigning the relative configurations of 3α-benzyloxy-jatroph-11E-ene and 7,8-seco-3α-benzyloxy-jatropha-11E-ene were summarized. Moreover, the hyperproliferation of T cells and keratinocytes is considered a key pathophysiology of psoriasis. Anti-proliferative activities against induced T/B lymphocytes and HaCaT cells were tested, and IC50 values of some compounds ranged from 6.7 to 31.5 µM. Compounds 7 and 11 reduced the secretions of IFN-γ and IL-2 significantly. Further immunofluorescence experiments and a docking study with NF-κB P65 showed that compound 13 interfered with the proliferation of HaCaT cells by inhibiting the NF-κB P65 phosphorylation at the protein level.


Subject(s)
Diterpenes , Euphorbia , Psoriasis , Euphorbia/chemistry , Humans , Psoriasis/drug therapy , Psoriasis/pathology , Diterpenes/pharmacology , Diterpenes/chemistry , Diterpenes/isolation & purification , Cell Proliferation/drug effects , Molecular Structure , Plant Extracts/pharmacology , Plant Extracts/chemistry , Keratinocytes/drug effects
14.
Org Lett ; 26(38): 8040-8044, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39264213

ABSTRACT

Although the transition-metal-catalyzed [3+2] cycloadditions to access isoxazoles have been described well, organocatalytic methods remain underdeveloped. Herein, we report the use of an organophosphine catalyst for the preparation of a series of isoxazoles with exceptional regioselectivity via the [3+2] cycloaddition of N-hydroxyamides and alkynes. The scope of this organocatalytic transformation is broad, tolerating numerous functional groups and proceeding uniformly in an environmentally friendly, simple, and efficient manner.

15.
HGG Adv ; : 100355, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39323095

ABSTRACT

Polygenic scores (PGS) are a promising tool for estimating individual-level genetic risk of disease based on the results of genome-wide association studies (GWAS). However, their promise has yet to be fully realized because most currently available PGS were built with genetic data from predominantly European-ancestry populations, and PGS performance declines when scores are applied to target populations different from the populations from which they were derived. Thus, there is a great need to improve PGS performance in currently under-studied populations. In this work we leverage data from two large and diverse cohorts the Million Veterans Program (MVP) and All of Us (AoU), providing us the unique opportunity to compare methods for building polygenic scores for multi-ancestry populations across multiple traits. We build polygenic scores for five continuous traits and five binary traits using both single-ancestry and multi-ancestry approaches with popular Bayesian PGS methods and population-specific GWAS results from the respective African, European, and Hispanic MVP populations. We evaluate these scores in three AoU populations genetically similar to the respective African, Admixed American, and European 1000 Genomes Project superpopulations. Using correlation-based tests, we make formal comparisons of the PGS performance across the multiple AoU populations. We conclude that approaches that combine GWAS data from multiple populations produce PGS that perform better than approaches which utilize smaller single-population GWAS results matched to the target population, and specifically that multi-ancestry scores built with PRS-CSx outperform the other approaches in the three AoU populations.

16.
Chem Commun (Camb) ; 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39324214

ABSTRACT

High entropy alloy nanoparticles encapsulated into nitrogen-doped carbon nanotubes show superior bifunctionality for the ORR and OER, evidenced by a battery performance of 214 mW cm-2, sustained for 200 h.

17.
Am J Rhinol Allergy ; : 19458924241282094, 2024 Sep 28.
Article in English | MEDLINE | ID: mdl-39340301

ABSTRACT

BACKGROUND: Sinonasal inverted papilloma (SNIP) is a benign epithelial tumor with distinctive histopathological features. However, the role of inflammation in SNIP remains poorly characterized. OBJECTIVES: This study aimed to compare the histopathological patterns and inflammatory characteristics of SNIP with those of chronic rhinosinusitis with nasal polyps (CRSwNPs) or normal ethmoid sinus mucosa. METHODS: Fifty-eight tissue biopsies were prospectively collected from 38 patients with SNIPs, 12 CRSwNPs, and 8 normal ethmoid sinus mucosae. SNIP was histopathologically divided into four grades based on the extent of epithelial remodeling. The immunohistochemical characteristics of epithelial remodeling (p63, CK5) and infiltration of inflammatory cells (eg, eosinophils, neutrophils, and macrophages) and cytokines (eg, interleukin-1ß, interleukin-6, and tumor necrosis factor-α) were analyzed. RESULTS: Among the 38 SNIPs, 21.1%, 36.8%, 23.7%, and 18.4% were grades I, II, III, and IV, respectively. The expression levels of p63 and CK5 were significantly higher in SNIP than in the other two groups (both, p < 0.05). Neutrophil and macrophage infiltration was more pronounced in SNIP and with differences among the four grades. The expression levels of inflammatory cytokines were significantly higher in the SNIP group than in the CRSwNP group. A positive correlation between the expression levels of p63 and inflammatory cytokines was observed in both SNIPs and CRSwNPs. CONCLUSION: Excessive epithelial remodeling is an important histological feature of SNIP; it is accompanied by sinonasal mucosal inflammation.

18.
Pain Ther ; 2024 Sep 28.
Article in English | MEDLINE | ID: mdl-39340712

ABSTRACT

This narrative review examines the therapeutic efficacy of peripheral nerve stimulation (PNS) in the treatment of neuropathic pain (NP), a type of pain arising from lesions or diseases of the somatosensory system with a global prevalence ranging from 6.90% to 10.00%. Traditional pharmacological interventions often fall short for many persons, highlighting the need for alternative treatments such as PNS, which has demonstrated significant promise with minimal side effects. The review summarizes the effectiveness of PNS in various NP conditions, including trigeminal neuralgia and postherpetic neuralgia, and underscores the need for further research to refine treatment approaches. The mechanism of PNS is discussed, involving the activation of non-nociceptive Aß fibers and modulation of neurotransmitters, and offering pain relief through both peripheral and central pathways. Despite the proven efficacy of PNS, challenges remain, including the need for randomized controlled trials and the optimization of stimulation parameters. The review concludes that PNS is a promising treatment modality for NP, warranting additional high-quality trials to solidify its role in clinical practice.

19.
Food Chem Toxicol ; : 115024, 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39341490

ABSTRACT

Methylmercury chloride (MMC) is a persistent heavy metal contaminant that can bioaccumulate in humans via the food chain, exerting detrimental effects on health. Nevertheless, the specific influence of MMC on oocyte meiotic maturation has yet to be elucidated. This research demonstrated that MMC exposure during the in vitro cultivation of mouse oocytes did not influence germinal vesicle breakdown but markedly decreased oocyte maturation rates. Subsequent analysis indicated that MMC exposure resulted in aberrant spindle morphology and disorganized chromosome alignment, alongside continuous activation of the spindle assembly checkpoint (SAC). However, MMC exposure didn't alter the localization pattern of microtubule-organizing center-associated proteins. MMC exposure considerably diminished the acetylation level of α-tubulin, signifying reduced microtubule stability. Additionally, MMC exposure disrupted the dynamic alterations of F-actin. MMC exposure didn't affect mitochondrial localization, mitochondrial membrane potential, adenosine triphosphate content or the concentrations of reactive oxygen species. Nonetheless, MMC exposure triggered DNA damage and modified histone modification levels. Consequently, the defects in oocyte maturation induced by MMC exposure can be attributed to impaired cytoskeleton dynamics and DNA damage. This study offers the first comprehensive elucidation of the negative impacts of MMC on oocyte maturation, highlighting the potential reproductive health risks associated with MMC exposure.

20.
Photodiagnosis Photodyn Ther ; 49: 104325, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39245305

ABSTRACT

BACKGROUND: Acne is a chronic inflammatory skin disease. Photodynamic therapy (PDT) is a highly effective and safe drug-device combination treatment, typically using red and blue light. However, direct comparisons of aminolevulinic acid (ALA)-based PDT using these two light sources are lacking. Therefore, we compared the efficacy and adverse effects of ALA-based 450 nm blue laser-mediated PDT (BL-PDT) and 630 ± 10 nm red light-emitting diode-mediated PDT (RL-PDT) in the treatment of moderate-to-severe acne vulgaris, including analyses of different lesion types. METHODS: Sixteen patients with moderate-to-severe acne vulgaris were recruited. All patients underwent BL-PDT on the left side of the face and RL-PDT on the right side. Treatments were administered thrice at 2-week intervals, and follow-up continued for 2 weeks after the final treatment. The average rates of improvement in inflammatory and non-inflammatory acne lesions, IGA (Investigator's Global Assessment) scales, and IGA success rates were calculated. In addition, adverse effects during and after each treatment were recorded. RESULTS: At the 2-week follow-up after the final treatment, the average rates of improvement in total acne, inflammatory, and non-inflammatory lesions were 48.0 %, 63.0 %, and 30.0 % in the BL-PDT group and 42.2 %, 58.1 %, and 27.5 % in the RL-PDT group, respectively. The IGA scores for the two groups decreased by 1.8 and 1.7 points, respectively, and the IGA success rate was 53.3 % in both groups. There were no significant differences between the BL-PDT and RL-PDT groups in any measure of effectiveness. However, the BL-PDT group exhibited more severe adverse effects, especially pain and hyperpigmentation. CONCLUSIONS: BL-PDT and RL-PDT have similar efficacies in moderate-to-severe acne vulgaris and are particularly effective for inflammatory acne lesions. RL-PDT benefits from milder adverse effects than those of BL-PDT.

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