To analyze the relationship between gut microbiota, metabolites and migraine: a two-sample Mendelian randomization study.

Background: It has been suggested in several observational studies that migraines are associated with the gut microbiota. It remains unclear, however, how the gut microbiota and migraines are causally related. Methods: We performed a bidirectional two-sample mendelian randomization study. Genome-wide association study (GWAS) summary statistics for the gut microbiota were obtained from the MiBioGen consortium (n = 18,340) and the Dutch Microbiota Project (n = 7,738). Pooled GWAS data for plasma metabolites were obtained from four different human metabolomics studies. GWAS summary data for migraine (cases = 48,975; controls = 450,381) were sourced from the International Headache Genetics Consortium. We used inverse-variance weighting as the primary analysis. Multiple sensitivity analyses were performed to ensure the robustness of the estimated results. We also conducted reverse mendelian randomization when a causal relationship between exposure and migraine was found. Results: LachnospiraceaeUCG001 (OR = 1.12, 95% CI: 1.05-1.20) was a risk factor for migraine. Blautia (OR = 0.93, 95% CI: 0.88-0.99), Eubacterium (nodatum group; OR = 0.94, 95% CI: 0.90-0.98), and Bacteroides fragilis (OR = 0.97, 95% CI: 0.94-1.00) may have a suggestive association with a lower migraine risk. Functional pathways of methionine synthesis (OR = 0.89, 95% CI: 0.83-0.95) associated with microbiota abundance and plasma hydrocinnamate (OR = 0.85, 95% CI: 0.73-1.00), which are downstream metabolites of Blautia and Bacteroides fragilis, respectively, may also be associated with lower migraine risk. No causal association between migraine and the gut microbiota or metabolites was found in reverse mendelian randomization analysis. Both significant horizontal pleiotropy and significant heterogeneity were not clearly identified. Conclusion: This Mendelian randomization analysis showed that LachnospiraceaeUCG001 was associated with an increased risk of migraine, while some bacteria in the gut microbiota may reduce migraine risk. These findings provide a reference for a deeper comprehension of the role of the gut-brain axis in migraine as well as possible targets for treatment interventions.

Association between the circulating very long-chain saturated fatty acid and cognitive function in older adults: findings from the NHANES.

BACKGROUND: Age-related cognitive decline has a significant impact on the health and longevity of older adults. Circulating very long-chain saturated fatty acids (VLSFAs) may actively contribute to the improvement of cognitive function. The objective of this study was to investigate the associations between arachidic acid (20:0), docosanoic acid (22:0), tricosanoic acid (23:0), and lignoceric acid (24:0) with cognitive function in older adults. METHODS: This study used a dataset derived from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). A total of 806 adults (≥ 60 years) were included who underwent comprehensive cognitive testing and plasma fatty acid measurements. Multivariable linear regression, restricted cubic spline (RCS), and interaction analyses were used to assess associations between VLSFAs and cognitive function. Partial Spearman' s correlation analysis was used to examine the correlations between VLSFAs and palmitic acid (16:0), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglycerides, systemic inflammatory markers, and dietary nutrients. RESULTS: Multivariable linear regression analysis, adjusting for sociodemographic, clinical conditions, and lifestyle factors, showed that 22:0 and 24:0 levels were positively associated with better global cognitive function (ß = 0.37, 95% confidence interval [CI] = 0.01, 0.73; ß = 0.73, 95% CI = 0.29, 1.2, respectively) as well as better CEARD-DR Z-score (ß = 0.82, 95% CI = 0.36, 1.3 and ß = 1.2, 95% CI = 0.63, 1.8, respectively). RCS analysis showed linear associations between higher 22:0 and 24:0 levels and better cognitive performance in both global cognitive function and CERAD-DR tests. CONCLUSIONS: The study suggests that higher levels of 22:0 and 24:0 are associated with better global cognitive function in older adults. 22:0 and 24:0 may be important biomarkers for recognizing cognitive impairment, and supplementation with specific VLSFAs (22:0 and 24:0) may be an important intervention to improve cognitive function. Further studies are needed to elucidate the underlying biological mechanisms between VLSFAs and cognitive function.

Diverse tillage practices with straw mulched management strategies to improve water use efficiency and maize productivity under a dryland farming system.

Straw mulching incorporation has a wide range of environmental benefits that make it an effective practice for sustainable agro-ecosystem in the semi-arid regions. There is an urgent need to improve the 13C-photosynthates distribution, water use efficiency (WUE) and maize canopy characteristics under the diverse tillage practices with straw mulched management strategies for sustainable intensification of maize production. The field study consists of three diverse tillage systems (RT: rotary tillage; CT, conventional tillage; MT, minimum tillage) with three straws mulching (NS: no straw mulch; SS: straw mulch on the soil surface; SI: straw incorporated into the soil) were assessed under the ridge-furrow rainfall harvesting system. Our results showed that the rotary tillage with straw incorporated into the soil significantly reduces the ET rate (11 %), and leaf rolling index; as a result considerably improves LAI, LEI, 13C-photosynthates distribution, N accumulation, and above ground biomass under various growth stages. The RTSI treatment significantly improved soil water storage, soil organic carbon (52 %, SOC), soil C storage (39 %, SCS), and NPK nutrients uptake (70 %, 62 %, and 69 %) of maize than observed for the rest of all other treatments, respectively. The RTSI treatment improves soil water balance, grain yield (53 %), biomass yield (37 %), WUEg (51 %), WUEb (35 %), nutrients uptake, and mitigating soil water depletion than the MTNS treatment. Although RTSS can achieve optimal soil water storage in the short term, RTSI has a great potential in improving soil carbon stability, canopy characteristics, soil water storage, and WUE, contributing to sustainable and intensive corn production in agricultural ecosystems in semi-arid regions.

Platelet Membrane-Coated r-SAK Improves Thrombolytic Efficacy by Targeting Thrombus.

Thrombolytic therapy is one of the most effective treatments for thrombus dissolution and recanalization of blocked vessels in thrombotic diseases. However, the application of the thrombolytic strategy has been limited due to unsatisfactory thrombolytic efficacy, relatively higher bleeding complications, and consequently restricted indications. Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology, which exhibits a better thrombolytic efficacy than urokinase and recombinant streptokinase. Inspired by the natural affinity of platelets in hemostasis and pathological thrombosis, we developed a platelet membrane (PM)-coated r-SAK (PM-r-SAK). Results from animal experiments and human in vitro studies showed that the PM-r-SAK had a thrombolytic efficacy equal to or better than its 4-fold dose of r-SAK. In a totally occluded rabbit femoral artery thrombosis model, the PM-r-SAK significantly shortened the initial recanalization time compared to the same dose and 4-fold dose of r-SAK. Regarding the recanalized vessels, the PM-r-SAK prolonged the time of reperfusion compared to the same dose and 4-fold dose of r-SAK, though the differences were not significant. An in vitro thrombolytic experiment demonstrated that the thrombolytic efficacy of PM-r-SAK could be inhibited by platelet-poor plasma from patients taking aspirin and ticagrelor. PM coating significantly improves the thrombolytic efficacy of r-SAK, which is related to the thrombus-targeting activity of the PM-r-SAK and can be inhibited by aspirin- and ticagrelor-treated plasma.

A population-based cohort of drug exposures and adverse pregnancy outcomes in China (DEEP): rationale, design, and baseline characteristics.

The DEEP cohort is the first population-based cohort of pregnant population in China that longitudinally documented drug uses throughout the pregnancy life course and adverse pregnancy outcomes. The main goal of the study aims to monitor and evaluate the safety of drug use through the pregnancy life course in the Chinese setting. The DEEP cohort is developed primarily based on the population-based data platforms in Xiamen, a municipal city of 5 million population in southeast China. Based on these data platforms, we developed a pregnancy database that documented health care services and outcomes in the maternal and other departments. For identifying drug uses, we developed a drug prescription database using electronic healthcare records documented in the platforms across the primary, secondary and tertiary hospitals. By linking these two databases, we developed the DEEP cohort. All the pregnant women and their offspring in Xiamen are provided with health care and followed up according to standard protocols, and the primary adverse outcomes - congenital malformations - are collected using a standardized Case Report Form. From January 2013 to December 2021, the DEEP cohort included 564,740 pregnancies among 470,137 mothers, and documented 526,276 live births, 14,090 miscarriages and 6,058 fetal deaths/stillbirths and 25,723 continuing pregnancies. In total, 13,284,982 prescriptions were documented, in which 2,096 chemicals drugs, 163 biological products, 847 Chinese patent medicines and 655 herbal medicines were prescribed. The overall incidence rate of congenital malformations was 2.0% (10,444/526,276), while there were 25,526 (4.9%) preterm births and 25,605 (4.9%) live births with low birth weight.

A case report of youth-onset lipoprotein glomerulopathy with APOE Chicago mutation.

BACKGROUND: This article reports an extremely rare case of lipoprotein glomerulopathy (LPG) with apolipoprotein E gene (APOE) Chicago mutation in a young Chinese male. Only five cases or families with APOE Chicago mutations have been reported in the literature. CASE PRESENTATION: The young male patient is manifested with nephrotic syndrome, accompanied by hyperlipidemia with a preferable increase in triglycerides and elevated ApoE level. Renal biopsy of the patient showed highly dilated glomerular capillaries filled with vacuolar lipids, segmentally fused podocyte foot processes, vacuolar degeneration of renal tubular epithelial cells and absence of electron-dense material, which indicates the diagnosis of LPG. Whole-exome gene sequencing identified the heterozygous mutation of NM_000041.4:c.494G > C (p.Arg165Pro), which is in the exon 4 of the APOE gene and also known as APOE Chicago mutation, a rare mutation of LPG. Further family pedigree gene analysis clarified that the mutation was inherited from the patient's mother, who does not have high ApoE levels or renal manifestations. This is also consistent with the incomplete penetrance of APOE gene mutations in LPG. Under lipid-lowering treatments, including a low-fat diet and fenofibrate, the patient's urinary protein was partially controlled, and the albumin level was recovered. CONCLUSION: Patients with nephrotic syndrome and elevated ApoE levels should be prompted into renal biopsy to avoid delay of appropriate treatment and unnecessary use of glucocorticoids. This case of LPG was diagnosed by renal biopsy and further verified with genetic sequencing. The timely diagnosis and treatment improved the patient's symptoms. This case is one of only six reported LPG cases or families with APOE Chicago mutation in the world.

Study on the Efficacy and Potential Mechanism of Topical Shen Bai Hair Growing Decoction against Androgenetic Alopecia Based on Ultrahigh Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry and RNA-seq.

Androgenetic alopecia (AGA) is a major problem that can happen to people of all ages, leading to psychological problems, such as anxiety and depression. Topical Shen Bai hair growing decoction (TSBHGD) is based on the pathogenesis of AGA, combined with Traditional Chinese Medicine theory, improved by the Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital according to its clinical treatment experience. This study was designed to demonstrate the therapeutic efficacy of TSBHGD against AGA, analyze the chemical components of TSBHGD as well as the skin-retained and blood-retained components in mice after topical administration of TSBHGD, and clarify the mechanism of its therapeutic efficacy. It was demonstrated that TSBHGD could suppress TNF-α and IL-6 levels and improve pathological phenomena such as hair loss, reduced follicle density, and dermal thickness caused by testosterone solution. Totally 35 components were identified in TSBHGD extracts, 12 skin-retained components were identified in drug-containing skin, and 7 blood-retained components were identified in drug-containing plasma, according to ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry. Transcriptomic sequencing revealed that some of the genes in AGA mice had altered expression patterns, which could be reversed by TSBHGD. Through network pharmacology analysis, it was found that TSBHGD mainly regulated eight signaling pathways, among which the apoptosis signaling pathway ranked first with a significance of 0.00149. Finally, both Bcl-2 and Caspase family proteins in the apoptosis signaling pathway were examined by Western blot. It was confirmed that TSBHGD could inhibit the apoptosis level in AGA mice's skin tissue to exert an anti-AGA effect. This will facilitate the development of new-generation herbal compound formulas with precise efficacy and provide novel ideas for AGA therapy.

Controllable Thrombolysis Using a Nanobubble-Imaging-Guided rtPA Targeted Delivery Strategy.

Objective: The objective of this work is to design and fabricate a novel multifunctional nanocarrier combining thrombus-targeted imaging and ultrasound-mediated drug delivery for the theranostics of thrombotic diseases. Impact Statement: This study develops a new technology that can accurately visualize the thrombus and deliver drugs with controllable properties to diagnose and treat thrombotic diseases. Introduction: Thrombotic diseases are a serious threat to human life and health. The diagnosis and treatment of thrombotic diseases have always been a challenge. In recent years, nanomedicine has brought new ideas and new methods for the theranostics of thrombotic diseases. However, there are also many problems need to be solved, such as biosafety and stability of nanocarriers, early diagnosis, and timely treatment of thrombotic diseases, difficulty in clinical translation. Methods: The S1P@CD-PLGA-rtPA nanobubbles (NBs) were prepared by integrating sulfur hexafluoride (SF6)-loaded poly (D, L-lactide-co-glycolide) (PLGA) NBs, cyclodextrin (CD), sphingosine-1-phosphate (S1P), and recombinant tissue plasminogen activator (rtPA). Results: S1P@CD-PLGA-rtPA NBs had rapid and excellent thrombosis targeting imaging performance based on the specific interaction of S1P-S1PR1 (sphingosine-1-phosphate receptor 1). Furthermore, S1P@CD-PLGA-rtPA NBs that specifically targeting to the thrombosis regions could also respond to external ultrasound to achieve accurate and efficient delivery of rtPA to enhance the thrombolysis effectiveness and efficiency. Conclusion: This study proposes a new idea and strategy of targeting thrombus in rats via the specific interaction of S1P-S1PR1. On this basis, the acoustic response properties of bubble carriers could be fully utilized by combining thrombus-specific targeted imaging and ultrasound-mediated drug delivery for effective thrombolysis, which is expected to be applied in targeted diagnosis and treatment of thrombotic diseases in the future.

New-onset metabolic syndrome is associated with accelerated renal function decline partially through elevated uric acid: an epidemiological cohort study.

Background: The burden of metabolic syndrome (MetS) continues to rise globally and is associated with complications of multiple organ systems. We aimed to identify the association between changes in MetS status and accelerated renal function progression through a regional epidemiological survey in China, thus discovering influence factors with treatable potential. Methods: This study was a population-based survey conducted in 2008 and 2014, assessing a representative sample of 5,225 individuals from rural areas of China. They were divided into four subgroups according to their MetS status in 2008 and 2014 (Never, Previously abnormal, New-onset, and Consistent). Multivariate logistic regression and stratification analysis evaluated the relationship between clinical factors and renal function decline under different MetS statuses. Smooth curve fitting further addressed the role of serum uric acid, illustrating the vital turning point of uric acid levels in the background of renal function deterioration. Results: Of all groups of MetS states, the new-onset MetS showed the most significant eGFR decline, with a 6.66 ± 8.21 mL/min/1.73 m2 decrease over 6 years. The population with newly-onset MetS showed a considerable risk increase in delta eGFR with a beta coefficient of 1.66 (95%CI=1.09-2.23) after necessary correction. In searching for the drivers, the strength of the association was significantly reduced after additional adjustment for uric acid levels (ß=0.91, 95%CI=0.35-1.45). Regarding the turning point, uric acid levels exceeding 426 µmol/L were more significantly associated with the stepped-up deterioration of kidney function for those with new-onset MetS. Conclusion: Metabolic syndrome demonstrated a solid correlation with the progression of renal function, particularly in those with newly-onset MetS status. In addition to the diagnostic components of MetS, hyperuricemia could be used as a marker to identify the high risk of accelerating eGFR decline early. Furthermore, we suggested a potential renal benefit for the newly-onset MetS population when maintaining their serum uric acid level below the criteria for asymptomatic hyperuricemia.

The impact of varying trolley case usage modes and weights on body posture.

OBJECTIVE: To study the body posture characteristics when walking with trolley case, and to explore the effects of different usage methods and weights of trolley case on body posture characteristics. METHODS: Fifteen subjects pushed and pulled(Condition 1 and 2) the case with three load weights of 10 %, 20 % and 30 % of their own body weight with 0 % no load as baseline for both conditions. The basic gait parameters, kinematic and kinetic data were collected using the VICON infrared motion capture system and a 3D force platform. Two repeated measures factor (condition×weight) analysis of variance was used for statistical analysis of the gait temporal and spatial parameters, as well as trunk angle, kinetic ground reaction force, shoulder joint force, and trunk moment. RESULTS: Significant condition*weight interactions were detected in DLST (Double Limb Stance Time) (F=5.341，P = 0.006), GRF (Ground Reaction Force) in frontal plane (F=10.507, p < 0.001) and vertical plane (F=3.751, p = 0.021), shoulder joint force in sagittal plane (F=21.129, p < 0.001), and flexion-extension angle of the trunk in the sagittal plane (F=4.888, p < 0.010). Significant main effects were detected in walking speed (F=35.842, p < 0.001), right support time (F=12.156, p < 0.001), left swing time (F=8.506, p < 0.001), left support time (F=1.122, p < 0.001), right step length (F=33.900, p < 0.001), and left step length (F=14.960, p < 0.001) under different weights. A significant main effect was detected in sagittal GRF (F=11.77, p < 0.001), trunk rotation angle (F=4.124, p = 0.016), amplitude of COM (F=2.993, p = 0.046), under different weights. CONCLUSION: When the weight of the case exceeds 20 % of the body weight, from the perspective of energy efficiency, the push method is more advantageous than the pull method. When walking with luggage, people tend to maintain the stability of their trunk posture by adjusting the force on their arms more often.

Platelet Membrane Nanocarriers Cascade Targeting Delivery System to Improve Myocardial Remodeling Post Myocardial Ischemia-Reperfusion Injury.

Although treatments for myocardial infarction have advanced significantly, the global mortality due to ischemia and subsequent reperfusion injury remains high. Here, a platelet (PLT) membrane nanocarrier (PL720) that encapsulates L-arginine and FTY720 to facilitate the cascade-targeted delivery of these substances to the myocardial injury site and enable the controlled release of L-arginine and FTY720 is developed. Such an innovative approach shows enhanced cardioprotection through multiple target strategies involved in ischemia-reperfusion injury and late reperfusion inflammation. During the ischemia-reperfusion phase, PL720 targets and accumulates in damaged coronary arteries. PL720 rapidly releases L-arginine, stimulating endothelial cells to produce NO, thereby dilating blood vessels and promoting blood flow recovery, while FTY720's sustained release exerts anti-apoptotic effects. During the late reperfusion inflammatory phase, PL720 is captured by circulating inflammatory monocytes and transported into a deeper ischemic myocardial lesion. PL720 promotes macrophage polarization and accelerates the inflammatory repair. Furthermore, the issue of bradycardia associated with the clinical use of FTY720 is innovatively relieved. Therefore, PL720 is a vascular injury and inflammation dual targeting strategy, exhibiting significant potential for multi-targeted therapy and clinical translation for cardiac injury.

The effects of Tripterygium wilfordii Hook F on renal outcomes in type 2 diabetic kidney disease patients with severe proteinuria: a single-center cohort study.

AIM: Tripterygium wilfordii Hook F (TwHF) has been shown to substantially reduce proteinuria in patients with diabetic kidney disease (DKD); however, the effect of TwHF on renal outcomes in DKD remains unknown. Accordingly, we aimed to establish the effects of TwHF on renal outcomes in patients with DKD. METHODS: Overall, 124 patients with DKD, induced by type 2 diabetes mellitus, with 24-h proteinuria > 2 g, and an estimated glomerular filtration rate > 30 mL/min/1.73 m2 were retrospectively investigated. The renal outcomes were defined as doubling serum creatinine levels or end-stage kidney disease. Kaplan-Meier curves and Cox regression analyses were performed to analyze prognostic factors for renal outcomes. RESULTS: By the end of the follow-up, renal outcomes were observed in 23 and 11 patients in the non-TwHF and TwHF groups, respectively (p = 0.006). TwHF significantly reduced the risk of renal outcomes (adjusted hazard ratio [HR] 0.271, 95% confidence interval [CI] 0.111-0.660, p = 0.004) in patients with chronic kidney disease (CKD) G3 (adjusted HR 0.274, 95%CI 0.081-0.932, p = 0.039). Based on the Kaplan-Meier analysis, 1- and 3-year proportions of patients without renal outcomes were significantly lower in the non-TwHF group than those in the TwHF group (92.8% vs. 95.5% and 47.2% vs. 76.8%, respectively; p = 0.0018). CONCLUSION: In DKD patients with severe proteinuria, TwHF could prevent DKD progression, especially in patients with CKD G3. A randomized clinical trial is needed to elucidate the benefits of TwHF on renal outcomes in patients with DKD.

Associations of hypertensive disorders of pregnancy with cognition, dementia, and brain structure: a Mendelian randomization study.

BACKGROUND: Observational studies have found associations between hypertensive disorders of pregnancy and an increased risk of cognitive dysfunction and reduced brain volume. However, the results of observational studies may have been influenced by confounding factors. This study applied two-sample Mendelian randomization (MR) to explore the causal associations of hypertensive disorders of pregnancy with cognition, dementia, and brain structure. METHODS: Summary data on hypertensive disorders of pregnancy and their main subtypes, cognition, dementia, and brain structure were obtained from recent European genome-wide association studies. We computed the inverse-variance weighted, MR-Egger, and weighted median MR estimates. Cochran's Q statistics and the MR-Egger intercept test were used to quantify the heterogeneity and horizontal pleiotropy of the instrumental variables. RESULTS: Genetically predicted preeclampsia or eclampsia was inversely associated with gray matter volume [beta = -0.072; 95% confidence interval (CI) = -0.131 to -0.014; P  = 1.53 × 10 -2 ]; possibly with brain volume (beta = -0.064; 95% CI = -0.117 to -0.012; P  = 1.68 × 10 -2 ). However, the association of hypertensive pregnancy disorders or gestational hypertension with brain structure was not significant. We did not find any significant association between hypertensive disorders of pregnancy, gestational hypertension, or preeclampsia or eclampsia and cognition and dementia-related outcomes. CONCLUSION: This study provided genetic evidence supporting an association between preeclampsia or eclampsia and reduced brain volume. This supports the view of PE as a risk factor for gray matter volume reduction.

Characteristics of T Cells in Single-Cell Datasets of Peripheral Blood and Cerebrospinal Fluid in Alzheimer's Disease Patients.

BACKGROUND: Alzheimer's disease (AD) is the most common type of dementia, causing a huge socioeconomic burden. In parallel with the widespread uptake of single-cell RNA sequencing (scRNA-seq) technology, there has been a rapid accumulation of data produced by researching AD at single-cell resolution, which is more conductive to explore the neuroimmune-related mechanism of AD. OBJECTIVE: To explore the potential features of T cells in the peripheral blood and cerebrospinal fluid of AD patients. METHODS: Two datasets, GSE181279 and GSE134578, were integrated from GEO database. Seurat, Monocle, CellChat, scRepertoire, and singleR packages were mainly employed for data analysis. RESULTS: Our analysis demonstrated that in peripheral blood, T cells were significantly expanded, and these expanded T cells were possessed effector function, such as CD8+TEMRA, CD4+TEMRA, and CD8+TEM. Interestingly, CD8+TEMRA and CD4+TEMRA cells positioned adjacently after dimensions reduction and clustering. Notably, we identified that the expanded T cells were developed from Naïve T cells and TCM cells, and TEM cells was in the intermediate state of this developing process. Additionally, in cerebrospinal fluid of AD patients, the amplified T cells were mainly CD8+TEMRA cells, and the number and strength of communication between CD4+TEM, CD8+TEM, and CD8+TEMRA were decreased in AD patients. CONCLUSIONS: Our comprehensive analyses identified the cells in cerebrospinal fluid from AD patients are expanded TEMRA or TEM cells and the TEMRA cells communicating with other immune cells is weakened, which may be an important immune feature that leads to AD.

Inhibition of Proliferation, Migration, and Invasion of Keloid Fibroblasts By miR-183-5p Through Downregulating EGR1 / Inhibición de la Proliferación, Migración e Invasión de Fibroblastos Queloides por miR-183-5p Mediante la Regulación Negativa de EGR1

SUMMARY: Keloid scar is a unique benign fibroproliferative tumor of the human skin. Previously, it was reported that early growth response 1 (EGR1), a transcription factor, promotes keloid fibrosis; however, the mechanism by which EGR1 modulates keloid formation was not elaborated. In this research, the specific function and the microRNA (miRNA) regulatory network of EGR1 in keloids was examined. Keloid fibroblasts (KFs) were transfected with EGR1-small interfering RNA (siEGR1), EGR1-overexpression plasmid (pcDNA3.1-EGR1), and microRNA (miR-183-5p)-mimics to regulate the expression of EGR1 and miR-183-5p. The study employed dual-luciferase reporter assays to explore the targeting regulation of miR-183-5p on EGR1. Additionally, Western blotting, flow cytometry, qRT-PCR, cell count kit-8 (CCK-8), transwell, and wound healing assays, and RNA sequencing were conducted. EGR1 was upregulated in KFs, and EGR1 silencing diminished proliferation, fibrosis, migration, invasion, and apoptosis of cells. In KFs, the expression of miR- 183-5p was reduced, leading to the inhibition of cell proliferation, migration, and invasion. Conversely, it enhanced apoptosis. By targeting EGR1, miR-183-5p partially counteracted the impact of EGR1 on migration, invasion, and fibrosis in KFs. The findings imply that miR-183-5p suppresses keloid formation by targeting EGR1. As a result, EGR1 holds promise as a potential therapeutic target for preventing and treating keloids.

La cicatriz queloide es un tumor fibroproliferativo benigno único de la piel humana. Anteriormente, se informó que la respuesta de crecimiento temprano 1 (EGR1), un factor de transcripción, promueve la fibrosis queloide; sin embargo, no se explicó el mecanismo por el cual EGR1 modula la formación de queloides. En esta investigación, se examinó la función específica y la red reguladora de microARN (miARN) de EGR1 en queloides. Se transfectaron fibroblastos queloides (KF) con ARN de interferencia pequeño de EGR1 (siEGR1), plásmido de sobreexpresión de EGR1 (pcDNA3.1-EGR1) y miméticos de microARN (miR-183-5p) para regular la expresión de EGR1 y miR-183. -5p. El estudio empleó ensayos de indicador de luciferasa dual para explorar la regulación dirigida de miR-183-5p en EGR1. Además, se realizaron pruebas de transferencia Western, citometría de flujo, qRT-PCR, kit de recuento celular-8 (CCK-8), transwell y curación de heridas, y secuenciación de ARN. EGR1 estaba regulado positivamente en KF, y el silenciamiento de EGR1 disminuyó la proliferación, fibrosis, migración, invasión y apoptosis de las células. En KF, la expresión de miR- 183-5p se redujo, lo que llevó a la inhibición de la proliferación, migración e invasión celular. Por el contrario, mejoró la apoptosis. Al apuntar a EGR1, miR-183-5p contrarrestó parcialmente el impacto de EGR1 en la migración, invasión y fibrosis en KF. Los hallazgos implican que miR-183-5p suprime la formación de queloides al apuntar a EGR1. Como resultado, EGR1 es prometedor como objetivo terapéutico potencial para prevenir y tratar los queloides.

Micro-plasma radiofrequency and silicone gel dressings for treating early post-traumatic facial scars: A retrospective study.

BACKGROUND: Although different options are available for treating post-traumatic facial scars, they remain a therapeutic challenge. AIM: To evaluate the safety and effectiveness of combined therapy using micro-plasma radiofrequency (MPRF) technology and silicone gel (SG) dressings for treating post-traumatic facial scars. METHODS: This retrospective study was conducted at a single center. Patients with facial injuries in the outpatient and emergency units of the Department of Plastic Surgery at our hospital underwent debridement and cosmetic sutures performed by the same surgeon from October 2020 to October 2021. In the first arm, patients with facial injuries were treated with MPRF technology and SG, and in the second arm, they were treated with SG dressings alone. We observed the safety and effectiveness of these treatments in both arms. RESULTS: A total of 32 patients with facial injuries were treated with MPRF technology and SG dressings (combined treatment group), and 28 patients were treated with SG dressings alone (SG group). After 6 months of treatment, the Vancouver Scar Scale scores of the combined treatment and SG groups were 1.38 ± 0.71 and 4.39 ± 0.50, respectively, and the difference was statistically significant (P < 0.01). After 6 months of treatment, the effectiveness rate in the combined treatment group was 93.8%, which was significantly higher than that in the SG group (67.9%), and the difference between the two groups was statistically significant (P < 0.05). No obvious adverse reactions occurred in the two arms. CONCLUSION: Treating early post-traumatic facial scars with combined MPRF technology and SG is significantly better than treating them with SG alone; moreover, the combined therapy is safe and effective.

The effect of theabrownins on the amino acid composition and antioxidant properties of hen eggs.

Pu-erh tea theabrownins (TBs) exert beneficial effect on egg quality and antioxidant properties of eggs, but the underlying mechanisms behind this response are unclear. In this study, we investigate the effect of TBs on egg antioxidative activity, amino acid and fatty acid profiles, and the underlying relationship between the TBs and oxidant-sensitive Nrf2 signaling pathway in laying hens. Eighty layers were fed a basal diet (control) and 400 mg/kg of TBs supplemented diet for 12 wk. TBs led to an increase in albumen height and Haugh unit (P < 0.05). The albumen lysine, valine, and tryptophan were higher in layers fed TBs, whereas yolk tryptophan, methionine, vitamin A, and α-tocopherol content were enhanced by TBs (P < 0.05). Eggs albumen and yolk showed higher total antioxidant capacity (T-AOC), reducing power (RP), and the scavenging rate of 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH), and lower MDA content than those of eggs from the control group (P < 0.05). Also, magnum Nrf2, hemeoxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), and Bcl2 expression were up-regulated by TBs, whereas magnum proapoptotic gene (Bax, caspase 3, Cyt C) were down-regulated by TBs (P < 0.05). Our findings suggest that TBs improved egg albumen quality and antioxidant activity, and the Nrf2-ARE pathway were found to be involved in this process.

Neuroinflammation catching nanobubbles for microglia-neuron unit modulation against epilepsy.

Epilepsy is a common neurological disease caused by synchronous firing of hyperexcitable neurons. Currently, patients with epilepsy are typically treated with antiseizure medicines that work by interrupting the hyperexcitability or hypersynchrony of localized neurons or by inhibiting excitatory neurotransmission. However, these drugs do not treat the underlying causes of epilepsy, and nearly one-third of patients have seizures that cannot be controlled by these medications. Animal and clinical evidence suggests that inflammation caused by neuronal and non-neuronal cells within the epilepsy lesion could play a central role in seizure disorders. Here we report a gas-filled nanobubble (NB) conjugated with diammonium glycyrrhizinate (DG) drugs and sphingosine-1-phosphate (S1P) molecules (S1P@DG-NBs) on the lipid shell for targeted therapy and real-time ultrasound visualization applications against neuroinflammatory injury. Affinity of S1P@DG-NBs for the S1P receptor endows these NBs with enhanced targeting capability to the neuroinflammatory microenvironment of epilepsy, where the DG drugs modulate endothelium-microglia-neuron inflammation by inhibiting high-mobility group box 1 molecules and downregulating the Toll-like receptor 4 signaling pathway, resulting in anti-inflammatory M2 microglia that exert anti-epilepsy effects. Our results show that this technology can enhance visualization of epileptic brain and deliver drugs with anti-inflammatory and immunomodulatory properties to ameliorate seizures symptoms.