Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology, cognition, and behavior in APP/PS1 mice.

JOURNAL/nrgr/04.03/01300535-202502000-00030/figure1/v/2024-05-28T214302Z/r/image-tiff In patients with Alzheimer's disease, gamma-glutamyl transferase 5 (GGT5) expression has been observed to be downregulated in cerebrovascular endothelial cells. However, the functional role of GGT5 in the development of Alzheimer's disease remains unclear. This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer's disease, as well as the underlying mechanism. We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer's disease (Aß1-42-treated hCMEC/D3 and bEnd.3 cells), as well as in the APP/PS1 mouse model. Additionally, injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits. Interestingly, increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-ß in the brains of APP/PS1 mice. This effect may be attributable to inhibition of the expression of ß-site APP cleaving enzyme 1, which is mediated by nuclear factor-kappa B. Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer's disease pathogenesis, and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice. These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer's disease.

Follow-up and histocompatibility observation of urethral reconstruction with different materials.

OBJECTIVE: Our objective is to observe the long-term surgical results of urethral reconstruction using either pedicled penile flaps or lingual mucosa grafts. We also assess the histocompatibility of the reconstructed urethra. MATERIALS AND METHODS: Clinical data of patients with anterior urethral stenosis undergoing urethra reconstruction by applying different materials were collected from 2014 to 2022 in the Second Hospital of Hebei Medical University. We assessed their efficacy and the occurrence of complications. Patients who required reoperation due to complications were selected. Sections of the reconstructed urethra created with various materials were excised during repair procedures. The excised tissues underwent hematoxylin-eosin staining and immunohistochemistry. Comparison with the original histological morphology was conducted to evaluate histocompatibility. RESULTS: 42 of the 55 patients were cured which showed a surgical success rate of 76.36%. The success rate of urethra reconstruction surgery utilizing lingual mucosa is 71.43% and that of surgeries using pedicled penis flaps is 79.41%. The long-term prognosis of the two groups is similar (P > 0.05). Observations show that the histological morphology of the original epithelium gradually disappeared, leading to adaptive changes to the urinary environment with favorable histocompatibility. CONCLUSION: The application of lingual mucosal and pedicled penis flaps for urethral reconstruction both have a high surgical success rate. The long-term follow-up results are positive. Both methods are viable for urethral reconstruction and exhibit favorable histocompatibility.

[Advantage analysis of modified day surgery procedure for concealed penis].

OBJECTIVE: The modified day surgery procedure was compared with traditional inpatient procedure and standard day surgery procedure of concealed penile surgery to investigate its advantages, as well as the feasibility of promoting it in our country. METHODS: Retrospective analyzing the clinical data between 135 cases of the concealed penis in children who underwent modified day surgery (day group) and 101 cases who underwent hospitalization surgery (hospitalization group) at the Second Hospital of Hebei Medical University and the results of follow-up.The modified day surgery procedure involves the establishment of dedicated day wards in each surgical department, where the patient's condition is monitored until 8 o'clock the following morning to assess their discharge eligibility.The children's clinical data was divided into two groups to compare clinical parameters, including age at surgery, bleeding volume, operation time, hospitalization expenses, day of hospitalization, and the occurrence of short-term complications before the initial dressing change after surgery.The satisfaction survey of the children was conducted among three distinct groups: the modified day group, the standard day group, and the hospitalization group enabling a comparison of satisfaction levels among these groups. RESULTS: The mean ages of the inpatient and day surgery groups were 8.92±4.42 years old and 11.85±4.43 years old, respectively. No significant differences were observed between these two groups regarding operation time, bleeding volume, and postoperative complications (P>0.05). Compared to the inpatient group, the mean inpatient time and the hospitalization cost of the day group decreased by 69% and 27%, respectively (P<0.05). The patients in the modified procedure group reported the highest satisfaction among the three groups. CONCLUSION: Modified day surgery procedure offers advantages over the standard day surgery procedure and traditional inpatient surgical procedures for the operative treatment of the concealed penis, which makes it suitable for large-scale popularization in China.

Effects of Exercise Training on PPARß/δ Expression in Skeletal Muscle of Rats with Spontaneous Hypertension.

PURPOSE: This study aimed to identify the relationship and mechanism between skeletal muscle peroxisome proliferator-activated receptor ß/δ (PPARß/δ) and spontaneous hypertension. METHODS: Rats were divided into four groups ( n = 10): spontaneous hypertensive rats exercise group (SHR-E), spontaneous hypertensive rats sedentary group (SHR-S), Wistar-Kyoto control rats exercise group (WKY-E), and Wistar-Kyoto control rats sedentary group (WKY-S). Although the sedentary groups were placed on the treadmill without moving during the training sessions, the exercise groups were forced to run on a treadmill for 8 wk, 1 h·d -1 , 5 d·wk -1 . After training, the density and area of gastrocnemius microvessels were observed. PPARß/δ, vascular endothelial growth factor A (VEGFA), superoxide dismutase 2 (SOD-2), and nitric oxide synthase in gastrocnemius were measured by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. RESULTS: Except the sixth week of age, the systolic blood pressure of SHR-S was significantly higher than that of WKY-S at all time periods. Exercise significantly reduced systolic blood pressure in SHR rats. Compared with the SHR-S group, the WKY-S group had significantly higher PPARß/δ protein level and density of skeletal muscle microvessels. Eight weeks of exercise increased the PPARß/δ, SOD-2, VEGFA, and microvessel density and area in the skeletal muscle of SHR. CONCLUSIONS: Exercise training promoted PPARß/δ mRNA and protein-level expression of PPARß/δ, SOD-2 and VEGFA in skeletal muscle, thus increasing the density and area of skeletal muscle blood vessels. These regulations contribute to the reduction of peripheral vascular resistance. This may be a potential mechanism of exercise to reduce blood pressure.

[Feasibility low cryptorchidism surgery following modified day surgical procedures].

OBJECTIVE: To explore the feasibility and safety of cryptorchidism surgery in the day surgery center. METHODS: This retrospective study included 122 cases of unilateral low cryptorchidism (ULC) and 27 cases of bilateral low cryptorchidism (BLC) treated by orchidopexy from July 2018 to July 2022 in the Second Hospital of Hebei Medical University. We divided the patients with ULC into an Ad (day surgery following modified day surgical procedures) and an Ac (conventional surgery) group, and those with BLC into a Bd and a Bc group. We analyzed the clinical data and compared the surgical parameters and patients' satisfaction between different groups. RESULTS: There were no statistically significant differences in the operation age, operation time, intraoperative blood loss, or postoperative complications between the Ad and Ac groups (P > 0.05), but the hospital stay and total cost were markedly reduced in the Ad group by 69% and 10%, respectively, compared with those in the Ac group (P < 0.05). No statistically significant differences were observed between the Bd and Bc groups in the operation age or intraoperative blood loss (P > 0.05), but the Bd group showed significant decreases in the operation time, hospital stay (62%) and total cost (14%) in comparison with the Bc group (P < 0.05). The satisfaction of the patients was remarkably higher in the former than in the latter group. CONCLUSION: Low cryptorchidism surgery following the modified day surgical procedures in the day surgery center is safe and feasible, with the advantages of lower cost and shorter hospital stay.

Triple-Configurational Magnetic Robot for Targeted Drug Delivery and Sustained Release.

Active targeted therapy for bowel cancer using untethered microrobots has attracted extensive attention. However, traditional microrobots face challenges, such as issues of mobility, biocompatibility, drug loading, sustained-release capabilities, and targeting accuracy. Here, we propose an untethered triple-configurational magnetic robot (TCMR) that is composed of three geometrically nested parts: actuation and guarding, anchoring and seeding, and drug release part. A targeting magnetic driving system actuates the TCMR along the predetermined trajectory to the target position. The pH-sensitive actuation and guarding part formed by electrodeposition is degraded in the intestinal environment and separates from the two other parts. A majority of magnetic nanoparticles encapsulated in this part are retrieved. The anchoring and seeding part anchors the lesion area and seeds the drug release part in the gaps of intestinal villi by hydrolysis. Ultimately, the drug release part containing the therapeutic completes the sustained release to prolong the duration of the therapeutic agent. Cytotoxicity and therapeutic tests reveal that TCMRs are biocompatible and suitable for targeted therapy and have good therapeutic performance. The newly designed TCMR will provide new ideas for targeted therapy, thus expanding the application scope of robotics technology in the biomedical field.

Absorption, metabolism, and bioactivity of vitexin: recent advances in understanding the efficacy of an important nutraceutical.

vitexin, an apigenin-8-C-glucoside, is widely present in numerous edible and medicinal plants. vitexin possesses a variety of bioactive properties, including antioxidation, anti-inflammation, anti-cancer, neuron-protection, and cardio-protection. Other beneficial health effects, such as fat reduction, glucose metabolism, and hepatoprotection, have also been reported in recent studies. This review briefly discusses the absorption and metabolism of vitexin, as well as its influence on gut microbiota. Recent advances in understanding the pharmacological and biological effects of vitexin are then reviewed. Improved knowledge of the absorption, metabolism, bioactivity, and molecular targets of vitexin is crucial for the better utilization of this emerging nutraceutical as a chemopreventive and chemotherapeutic agent.

HOXA5 overexpression promotes osteosarcoma cell apoptosis through the p53 and p38α MAPK pathway.

Osteosarcoma is the most common malignant bone tumor in children and adolescents. Aberrant expression of HOXA5 results in various diseases, including cancers. However, the specific function and molecular mechanism of HOXA5 in osteosarcoma is not fully understood. In the present study, we focused on HOXA5 in U2OS and MG63 cells in vitro. We observed lower expression of HOXA5 in U2OS, MG63, and SaOS2 human osteosarcoma cells, compared with hFOB1.19 human osteoblastic cells. HOXA5 overexpression in U2OS and MG63 cells markedly reduced cell survival and proliferation and elevated cell apoptosis and caspase-3 activity. HOXA5 also activated the p38α MAPK pathway by increasing p53. Treating U2OS and MG63 cells with the p53 inhibitor α-pifithrin or the p38α MAPK inhibitor SB203580 led to higher cell survival and proliferation and lower cell apoptosis, compared with the pcDNA3.1-HOXA5 group. In conclusion, our study showed that the p53 and p38α MAPK signal axis facilitated HOXA5's role in inhibiting growth and stimulating apoptosis of osteosarcoma cells.

Does Kinematic Alignment Improve Short-Term Functional Outcomes after Total Knee Arthroplasty Compared with Mechanical Alignment? A Systematic Review and Meta-analysis.

This meta-analysis was conducted to study whether kinematically aligned total knee arthroplasty (TKA) improves short-term functional outcomes compared with mechanical alignment without changing the hip-knee-ankle angle. Prospective cohort studies were searched from electronic literature databases, including PubMed, Web of Science, Embase (Ovid interface), and Cochrane Library (Ovid interface). Total 1,159 records were identified. Six trials involving 561 patients were eligible for data extraction and meta-analysis. The included studies recorded outcomes in the follow-up range from 6 to 34 months. Primary outcomes were to assess the functional outcomes in follow-up, and KA group achieved better performance on WOMAC score (mean difference [MD] = -18.82, 95% CI: -16.06 to -5.58), knee function score (MD = 7.23, 95% CI: 0.52-13.94), Oxford knee score (MD = 4.76, 95% CI: 0.40-9.12), and knee range of flexion (MD = 4.48, 95% CI: 2.09-6.86), whereas other parameters including Knee Society score, knee range of extension, VAS pain score, and the occurrence of the complications were without significant difference (p > 0.05). Second outcomes evaluated the perioperative clinic indexes. Our meta-analysis showed that KA group had a shorter time of operation (MD = -15.44, 95% CI: -27.47 to -3.71) and a longer walk distance before discharge (MD = 53.24, 95% CI: 21.32-85.15) when compared with the MA group, whereas the change in hemoglobin, incision length, knee range of flexion before discharge, and length of stays were without significant difference (p > 0.05). Third outcomes were used to analyze the alignment data. Our study showed that KA had larger angles of femoral component and mechanical axis of the femur (MD = -1.95,95% CI: -2.77 to -1.13), tibial component and mechanical axis of tibia (MD = 2.06, 95% CI: 1.43-2.70), anatomic knee angle (MD = -0.72, 95% CI: -1.33 to -0.11), and operative limb alignment (MD = -1.97, 95% CI: -2.50 to -1.45,) compared with the MA group, but the hip-knee-ankle angles between the two groups were similar. KA provided better functional outcomes and better flexion following short-term follow-up of TKA. However, longer-term follow-up and larger sample studies are needed to put into research in the future.

One-pot, solid-phase synthesis of magnetic multiwalled carbon nanotube/iron oxide composites and their application in arsenic removal.

Carbon nanotubes (CNTs) functionalized with magnetic nanoparticles are attractive for environmental remediation applications due to their high specific surface area conducive for adsorption of water contaminants and the possibility of recovering these nanohybrids after remediation using an external magnetic field. Most of existing methods for synthesizing magnetic iron oxide/CNTs (MIO-CNTs) composites are carried out in the liquid medium and are tedious, uneconomical, and environmentally unfriendly. Herein, we report a one-pot solid-phase route to synthesize MIO-CNTs composites based on pristine CNTs. MIO-CNTs possess a high specific surface area, good dispersibility, and desirable magnetic properties, making them promising as adsorbents for arsenic removal. The maximum arsenic adsorption capacities are 47.41 and 24.05 mg g(-)(1) for As(V) and As(III), respectively. These values are among the highest for carbon-based materials. Oxygen-containing groups on the surface of MIO-CNTs play a crucial role in arsenic adsorption. This work is very important for the practical applications of pristine CNTs containing catalyst nanoparticles without the need of purifications.

A facile one-pot method for synthesis of low-cost iron oxide/activated carbon nanotube electrode materials for lithium-ion batteries.

We designed a facile one-pot method to synthesize iron oxide/activated carbon nanotubes (IO/ACNTs) using as-prepared carbon nanotubes (APCNTs) modified by alkali solid-activation. The open-ended CNTs and iron oxide loading could be realized in one step. The resulting IO/ACNT hybrids, as an anode material for lithium-ion batteries (LIBs), exhibited high reversible lithium storage capacity and excellent rate capability, which make APCNTs potentially useful for large-scale applications in LIBs.