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1.
J Arthroplasty ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38823520

ABSTRACT

BACKGROUND: Modular reconstruction systems based on porous tantalum (PT) prosthetic components have been increasingly used for the treatment of complex acetabular bone defects in revision total hip arthroplasty (rTHA). We report a novel technique that applies a revision cup as a "super-augment" to form a "double-cup" construct for Paprosky type III defects. METHOD: A retrospective review was conducted on rTHA cases, comparing those treated with double-cup constructs (DC group, n = 48) to those treated with PT shells and augments (PT group, n = 48). All procedures were performed at the same institute between 2017 and 2022. Clinical outcome evaluation utilized the Harris Hip Score (HHS), Oxford Hip Score (OHS), and 36-Item Short Form Survey (SF-36). Preoperative and postoperative radiographic assessments measured hip center of rotation (COR) position and leg length discrepancy (LLD). Additionally, postoperative complications and implant survivorship were monitored during the follow-up period. RESULTS: The clinical outcomes improved substantially in both groups, which showed no significant difference in HHS (P = 0.786), OHS (P = 0.570), and SF-36 (P = 0.691). Compared to the PT group, the reconstruction COR was significantly closer to the anatomic COR (vertical distance: 2.630 versus 7.355 mm, P = 0.0034; horizontal distance: 1.881 versus -6.413 mm, P < 0.0001) in Paprosky IIIB type defects. Additionally, postoperative LLD was less in the DC group (-8.252 versus -1.821 mm, P = 0.0008). Dislocation was the main complication in the DC group, and only one patient received re-revision due to repeated dislocation. The cumulative survival rate of the DC group (100%; 95% CI [confidence interval] 100) was better than the PT group (83.4%; 95% CI 70.5 to 98.6) when re-revisions for aseptic loosening were the endpoint (P = 0.046). CONCLUSIONS: The double-cup construct is a reliable revision technique for the reconstruction of Paprosky type III bone defects. Although dislocation remains challenging, the biomechanically superior restoration achieved by this technique lowers the risk of aseptic loosening.

2.
J Hosp Infect ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38823643

ABSTRACT

PURPOSE: Antimicrobial-coated sutures are one of the strategies to avoid surgical site infection (SSI) caused by microbial colonization on the surface of surgical sutures. This study aims to investigate the effectiveness of antimicrobial-coated sutures in reducing SSI and develop the latest systematic evaluation evidence for clinical SSI prevention and the use of antimicrobial-coated sutures. METHODS: We searched the databases of Medline, Embase, CINAHL, Cochrane, African Index Medicus, and WHO Global Health from October 10th, 1990 to March 3rd, 2023 with language restricted to English, Spanish, and French. Meta-analysis was used to evaluate the impact of antimicrobial-coated sutures on SSI and whether their effectiveness is influenced by the type of sutures or wounds. Subgroup analyses were conducted based on type of sutures and wounds. Finally, quality of the retrieved evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: 26 RCTs and 9 OBSs met the inclusion criteria. Antimicrobial sutures significantly reduced SSI risk (RCTs: OR: 0.74, 95% CI [0.63-0.87], p = 0.0002; OBSs: OR: 0.61, 95% CI [0.48-0.76], p < 0.0001). Only subgroup analysis of Polydioxanone Suture (PDS) Plus vs. PDS, Vicryl Plus vs. Vicryl and mixed wounds revealed consistent results in favour of antimicrobial-coated sutures. According to GRADE, the quality of RCTs evidence is moderate, while that of OBSs evidence is low. CONCLUSION: Antimicrobial-coated sutures are effective in reducing the risk of postoperative SSI among a large number of surgical patients. However, the available evidence is of moderate/low quality and many studies had conflicts of interest.

3.
Biomater Sci ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38842122

ABSTRACT

Oxidative stress (OS) plays an important role in the emergence and prevention of neurodegenerative diseases, such as Alzheimer's disease (AD). Excess reactive oxygen species (ROS) accumulated in a neuronal cell can lead to OS, producing cell injury and death. Seeking nanoantioxidants against AD-related oxidative stress has attracted a lot of attention, especially those potential antioxidant agents derived from natural polyphenols. However, the transformation of abundant plant polyphenols to antioxidative biomaterials against OS is still challenging. In this work, we report a new method to transform amorphous tannic acid (TA) into tailorable shaped ellagic acid (EA) crystalline particles without using an organic solvent. EA crystalline particles were generated from TA, which underwent a chemical transformation, in situ metal phenolic coordination and acid-induced assembly process, and the size and shape could be controlled by varying the amount of acid. As-prepared EA crystalline particles showed excellent stability in water and lysosomal mimicking fluid and possess unique fluorescence properties and a strong response in mass spectrometry, which is beneficial for their imaging analysis in cells and tissues. More importantly, EA particles have shown significant H2O2-related ROS scavenging ability, a high cellular uptake capacity, an excellent neuroprotective effect in PC12 cells, a high drug loading capacity and BBB permeability to enter the brain. Our study suggested that the EA crystalline particles show great potential for OS-mediated AD treatment.

4.
Biomater Res ; 28: 0031, 2024.
Article in English | MEDLINE | ID: mdl-38845842

ABSTRACT

The abdominal wall plays a crucial role in safeguarding the internal organs of the body, serving as an essential protective barrier. Defects in the abdominal wall are common due to surgery, infection, or trauma. Complex defects have limited self-healing capacity and require external intervention. Traditional treatments have drawbacks, and biomaterials have not fully achieved the desired outcomes. Hydrogel has emerged as a promising strategy that is extensively studied and applied in promoting tissue regeneration by filling or repairing damaged tissue due to its unique properties. This review summarizes the five prominent properties and advances in using hydrogels to enhance the healing and repair of abdominal wall defects: (a) good biocompatibility with host tissues that reduces adverse reactions and immune responses while supporting cell adhesion migration proliferation; (b) tunable mechanical properties matching those of the abdominal wall that adapt to normal movement deformations while reducing tissue stress, thereby influencing regulating cell behavior tissue regeneration; (c) drug carriers continuously delivering drugs and bioactive molecules to sites optimizing healing processes enhancing tissue regeneration; (d) promotion of cell interactions by simulating hydrated extracellular matrix environments, providing physical support, space, and cues for cell migration, adhesion, and proliferation; (e) easy manipulation and application in surgical procedures, allowing precise placement and close adhesion to the defective abdominal wall, providing mechanical support. Additionally, the advances of hydrogels for repairing defects in the abdominal wall are also mentioned. Finally, an overview is provided on the current obstacles and constraints faced by hydrogels, along with potential prospects in the repair of abdominal wall defects.

5.
Cancer Cell Int ; 24(1): 195, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38835070

ABSTRACT

BACKGROUND: Investigating the unexplored territory of lncRNA m6A modification in colorectal cancer (CRC) vasculature, this study focuses on LINC01106 and YTHDF1. METHODS: Clinical assessments reveal upregulated LINC01106 promoting vascular generation via the miR-449b-5p-VEGFA pathway. RESULTS: YTHDF1, elevated in CRC tissues, emerges as an adverse prognostic factor. Functional experiments showcase YTHDF1's inhibitory effects on CRC cell dynamics. Mechanistically, Me-CLIP identifies m6A-modified LINC01106, validated as a YTHDF1 target through Me-RIP. CONCLUSIONS: This study sheds light on the YTHDF1-mediated m6A modification of LINC01106, presenting it as a key player in suppressing CRC vascular generation.

6.
J Appl Stat ; 51(7): 1251-1270, 2024.
Article in English | MEDLINE | ID: mdl-38835825

ABSTRACT

The accelerated hazards model is one of the most commonly used models for regression analysis of failure time data and this is especially the case when, for example, the hazard functions may have monotonicity property. Correspondingly a large literature has been established for its estimation or inference when right-censored data are observed. Although several methods have also been developed for its inference based on interval-censored data, they apply only to limited situations or rely on some assumptions such as independent censoring. In this paper, we consider the situation where one observes case K interval-censored data, the type of failure time data that occur most in, for example, medical research such as clinical trials or periodical follow-up studies. For inference, we propose a sieve borrow-strength method and in particular, it allows for informative censoring. The asymptotic properties of the proposed estimators are established. Simulation studies demonstrate that the proposed inference procedure performs well. The method is applied to a set of real data set arising from an AIDS clinical trial.

7.
J Environ Sci Health B ; : 1-12, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847499

ABSTRACT

Sulfonamide antibiotics (SAs) are widely used antimicrobial agents in livestock and aquaculture, and most of them entering the animal's body will be released into the environment as prodrugs or metabolites, which ultimately affect human health through the food chain. Both acid deposition and salinization of soil may have an impact on the migration and degradation of antibiotics. Sulfamethazine (SM2), a frequently detected compound in agricultural soils, has a migration and transformation process in the environment that is closely dependent on environmental pH. Nevertheless, scarcely any studies have been conducted on the effect of soil pH changes on the environmental behavior of sulfamethazine. We analyzed the migration and degradation mechanisms of SM2 using simulation experiments and ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) techniques. The results showed that acidic conditions limited the vertical migration of sulfadimidine, and SM2 underwent different reaction processes under different pH conditions, including S-C bond breaking, S-N bond hydrolysis, demethylation, six-membered heterocyclic addition, methyl hydroxylation and ring opening. The study of the migration pattern and degradation mechanism of SM2 under different pH conditions can provide a solid theoretical basis for assessing the pollution risk of sulfamethazine degradation products under acid rain and saline conditions, and provide a guideline for remediation of antibiotic contamination, so as to better prevent, control and protect groundwater resources.

8.
PLoS One ; 19(5): e0300153, 2024.
Article in English | MEDLINE | ID: mdl-38722905

ABSTRACT

In an attribute-based strong designated verifier signature, a signer who satisfies the access structure signs the message and assigns it to a verifier who satisfies the access structure to verify it, which enables fine-grained access control for signers and verifiers. Such signatures are used in scenarios where the identity of the signer needs to be protected, or where the public verifiability of the signature is avoided and only the designated recipient can verify the validity of the signature. To address the problem that the overall overhead of the traditional attribute-based strong designated verifier signature scheme is relatively large, an efficient attribute-based strong designated verifier signature scheme based on elliptic curve cryptography is proposed, as well as a security analysis of the new scheme given in the standard model under the difficulty of the elliptic curve discrete logarithm problem (ECDLP). On the one hand, the proposed scheme is based on elliptic curve cryptography and uses scalar multiplication on elliptic curves, which is computationally lighter, instead of bilinear pairing, which has a higher computational overhead in traditional attribute-based signature schemes. This reduces the computational overhead of signing and verification in the system, improves the efficiency of the system, and makes the scheme more suitable for resource-constrained cloud end-user scenarios. On the other hand, the proposed scheme uses LSSS (Linear Secret Sharing Schemes) access structure with stronger access policy expression, which is more efficient than the "And" gate or access tree access structure, making the computational efficiency of the proposed scheme meet the needs of resource-constrained cloud end-users.


Subject(s)
Computer Security , Algorithms , Humans
10.
Postgrad Med ; : 1-11, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38753519

ABSTRACT

OBJECTIVES: This study sought to investigate the relationship between the systemic inflammatory response index (SIRI) and bone mineral density (BMD), osteoporosis, and future fracture risk in elderly hypertensive patients. METHODS: Elderly hypertensive patients (age ≥60 years) who attended our hospital between January 2021 and December 2023 and completed BMD screening were included in the study. Analyses were performed with multivariate logistic and linear regression. RESULTS: The multiple linear regression indicated that SIRI levels were significantly negatively correlated with lumbar 1 BMD (ß = -0.15, 95% CI: -0.24, -0.05), lumbar 2 BMD (ß = -0.15, 95% CI: -0.24, -0.05), lumbar 3 BMD (ß = -1.35, 95% CI: -0.23, -0.02), lumbar 4 BMD (ß = -0.11, 95% CI: -0.30, -0.10), femur neck BMD (ß = -0.11, 95% CI: -0.18, -0.05) and Ward's triangle BMD (ß = -0.12, 95% CI: -0.20, -0.05) among elderly hypertensive patients, after fully adjusting for confounders. Furthermore, we observed that SIRI was positively associated with future fracture risk in elderly hypertensive patients. Specifically, SIRI was associated with an increased risk of major osteoporotic fractures (ß = 0.33) and hip fractures (ß = 0.25). The logistic regression analysis indicated that there is an association between the SIRI level and an increased risk of osteoporosis (OR = 1.60, 95% CI = 1.37, 1.87), after fully adjusting for confounders. CONCLUSIONS: Our findings indicate a potential association between SIRI and BMD, osteoporosis, and the risk of future fractures in elderly hypertensive patients. However, further studies are warranted to confirm these findings.

11.
BMC Public Health ; 24(1): 1309, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38745323

ABSTRACT

BACKGROUND: The National Drug Price Negotiation (NDPN) policy has entered a normalisation stage, aiming to alleviate, to some extent, the disease-related and economic burdens experienced by cancer patients. This study analysed the use and subsequent burden of anticancer medicines among cancer patients in a first-tier city in northeast China. METHODS: We assessed the usage of 64 negotiated anticancer medicines using the data on the actual drug deployment situation, the frequency of medical insurance claims and actual medication costs. The affordability of these medicines was measured using the catastrophic health expenditure (CHE) incidence and intensity of occurrence. Finally, we used the defined daily doses (DDDs) and defined daily doses cost (DDDc) as indicators to evaluate the actual use of these medicines in the region. RESULTS: During the study period, 63 of the 64 medicines were readily available. From the perspective of drug usage, the frequency of medical insurance claims for negotiated anticancer medicines and medication costs showed an increasing trend from 2018 to 2021. Cancer patients typically sought medical treatment at tertiary hospitals and purchased medicines at community pharmacies. The overall quantity and cost of medications for patients covered by the Urban Employee Basic Medical Insurance (UEBMI) were five times higher than those covered by the Urban and Rural Resident Medical Insurance (URRMI). The frequency of medical insurance claims and medication costs were highest for lung and breast cancer patients. Furthermore, from 2018 to 2021, CHE incidence showed a decreasing trend (2.85-1.60%) under urban patients' payment capability level, but an increasing trend (11.94%-18.42) under rural patients' payment capability level. The average occurrence intensities for urban (0.55-1.26 times) and rural (1.27-1.74 times) patients showed an increasing trend. From the perspective of drug utilisation, the overall DDD of negotiated anticancer medicines showed an increasing trend, while the DDDc exhibited a decreasing trend. CONCLUSION: This study demonstrates that access to drugs for urban cancer patients has improved. However, patients' medical behaviours are affected by some factors such as hospital level and type of medical insurance. In the future, the Chinese Department of Health Insurance Management should further improve its work in promoting the fairness of medical resource distribution and strengthen its supervision of the nation's health insurance funds.


Subject(s)
Antineoplastic Agents , Drug Costs , Insurance, Health , Humans , China , Antineoplastic Agents/economics , Antineoplastic Agents/therapeutic use , Drug Costs/statistics & numerical data , Insurance, Health/economics , Insurance, Health/statistics & numerical data , Neoplasms/drug therapy , Neoplasms/economics , Female , Male , Negotiating , Health Expenditures/statistics & numerical data , Middle Aged
12.
Article in English | MEDLINE | ID: mdl-38819328

ABSTRACT

OBJECTIVE: Robotic surgery is being increasingly used for colorectal cancer surgery. However, its utility versus laparoscopic surgery in older patients is unclear. We systematically examined evidence to assess the differences in short-term outcomes of robotic versus laparoscopic surgery for colorectal cancer in older patients. MATERIAL AND METHODS: Comparative studies published on PubMed, Web of Science, Embase, and CENTRAL databases were searched up to August 30th, 2023. RESULTS: Seven studies totaling 14,043 patients were included. Meta-analysis showed no difference in the operation time between the robotic and laparoscopic groups. Meta-analysis of ClavienDindo complications showed no difference between the robotic and laparoscopic groups for grades I and II or grades III and IV complications. Similarly, conversion to open surgery, reoperation rates and length of hospital stay were not significantly different between the two groups. Readmission rates and mortality rates were significantly lower with robotic surgery. CONCLUSION: This first meta-analysis comparing outcomes of robotic and laparoscopic surgery in older colorectal cancer patients shows that both approaches result in no difference in operating time, complication rates, conversion to open surgery, reoperation rates, and LOS. Scarce data shows that mortality and readmission rates may be lower with robotic surgery.

13.
JCI Insight ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38805402

ABSTRACT

BACKGROUND: Identifying patients with acute kidney injury (AKI) who are at higher risk of chronic kidney disease (CKD) progression at time of AKI diagnosis remains a major challenge in clinical practice. METHODS: Kidney transcriptome sequencing was applied to identify the top up-regulated genes in mice with AKI. The product of the top-ranked gene was identified in the tubular cells and urine both in mouse and human AKI. Data from two cohorts of patients with a prehospitalization estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73m2 who survived for at least 90 days after AKI were used to derive and validate multivariable prediction models. AKI to CKD progression was defined as a persistent eGFR < 60 ml/min/1.73m2 and with a minimum 25% reduction from baseline eGFR 90 days after AKI in patients with prehospitalization eGFR ≥ 60 ml/min/1.73m2. AKI to advanced CKD was defined by a sustained reduction of eGFR < 30 ml/min/1.73m2 90 days after AKI in those with prehospitalization eGFR 45-60 ml/min/1.73m2. RESULTS: Kidney cytokeratin 20 (CK20) was up-regulated in injured proximal tubular cells and detectable in urine within 7 days after AKI. High concentrations of urinary CK20 (uCK20) were independently associated with the severity of histological AKI and the risk of AKI to CKD or advanced CKD progression. In Test set, the AUC of uCK20 for predicting AKI to CKD or advanced CKD was 0.80, outperformed currently used biomarkers for detecting kidney tubular injury. Addition of uCK20 to an established clinical model improved the ability for predicting AKI-CKD progression with an AUC of 0.90, and largely improved the risk reclassification. CONCLUSION: This finding highlighted uCK20 as a useful predictor for AKI to CKD progression, and may provide a tool to early identify patients at high risk of CKD following AKI. FUNDING: The National Natural Science Foundation of China (Key Program).

14.
Int J Clin Pharm ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38814514

ABSTRACT

BACKGROUND: Camrelizumab combined with rivoceranib has been proven effective for treating unresectable hepatocellular carcinoma (uHCC). However, their higher prices than sorafenib could impose a substantial economic burden on patients. AIM: This study aimed to evaluate the relative cost-effectiveness of the combination of camrelizumab and rivoceranib versus sorafenib as first-line therapy for patients with uHCC from the perspective of the US and Chinese payers. METHOD: Using data from the CARES-310 trial, a partitioned survival model (PSM) was developed, considering the perspectives of the US and Chinese payers. The model employed a 15-year time horizon and a biweekly cycle. Direct medical costs and utility data were collected from previous studies and open-access databases. Primary outcomes included quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER). Price simulations, sensitivity analyses, and subgroup analyses were conducted. RESULTS: The ICER for the US and China was $122,388.62/QALY and $30,410.56/QALY, respectively, falling below the willingness-to-pay (WTP) thresholds of $150,000/QALY for the US and $35,898.87/QALY for China. Price simulations indicated the cost-effectiveness of camrelizumab plus rivoceranib when the price of camrelizumab (200 mg) remained below $6275.19 in the US and $558.09 in China. The primary determinant of cost-effectiveness in both regions was the cost of camrelizumab. CONCLUSION: The combination of camrelizumab and rivoceranib is a cost-effective first-line therapy for uHCC in both the US and China. Lowering their prices could significantly influence their cost-effectiveness and accessibility to patients. These findings will guide clinicians in treating uHCC and help decision-makers formulate value-based drug pricing strategies.

15.
Sci Rep ; 14(1): 10735, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730029

ABSTRACT

The humidity has often been measured through a single point sensor. Where, the humidity could be varied at different locations as well as depending on environmental conditions. The present paper developed the dual point humidity measuring sensor by using a polymer optical fiber (POF) based on a single illuminating fiber. The sensor's basic structure is to twist two fibers and bend them at a certain radius. However, the dual point sensor is developed through the cascading of twisted micro bend (TMB-1 and TMB-2). The twisting of fibers couples the light from one fiber to another fiber through the side coupling method. An increase in the humidity level leads to a change in the reflective index, which helps to get variation in coupled light intensity. To measure the humidity, the dual point sensors are placed into the control humidity chamber at two random positions. The power reading variation is significantly linear when the humidity level increases from 30 to 80%. The sensor has a fast response of about 1 s and a recovery time of about 4 s. Furthermore, the chemical coating is applied to improve the sensor's sensitivity. Between 30 and 80% range of humidity, the both sensors of dual point TMB-1 and TMB-2 have appropriate sensitivity and detection limits, which is about 680.8 nW/% and 763.9 nW/% and 1.37% and 1.98%, respectively. To measure the humidity at variable positions, the present dual points humidity sensor is well-stable, easy, and straightforward, which uses a less expensive method.

16.
Nat Commun ; 15(1): 3970, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730227

ABSTRACT

High-altitude hypoxia acclimatization requires whole-body physiological regulation in highland immigrants, but the underlying genetic mechanism has not been clarified. Here we use sheep as an animal model for low-to-high altitude translocation. We generate multi-omics data including whole-genome sequences, time-resolved bulk RNA-Seq, ATAC-Seq and single-cell RNA-Seq from multiple tissues as well as phenotypic data from 20 bio-indicators. We characterize transcriptional changes of all genes in each tissue, and examine multi-tissue temporal dynamics and transcriptional interactions among genes. Particularly, we identify critical functional genes regulating the short response to hypoxia in each tissue (e.g., PARG in the cerebellum and HMOX1 in the colon). We further identify TAD-constrained cis-regulatory elements, which suppress the transcriptional activity of most genes under hypoxia. Phenotypic and transcriptional evidence indicate that antenatal hypoxia could improve hypoxia tolerance in offspring. Furthermore, we provide time-series expression data of candidate genes associated with human mountain sickness (e.g., BMPR2) and high-altitude adaptation (e.g., HIF1A). Our study provides valuable resources and insights for future hypoxia-related studies in mammals.


Subject(s)
Altitude Sickness , Altitude , Gene Expression Regulation , Hypoxia , Animals , Altitude Sickness/genetics , Altitude Sickness/metabolism , Sheep , Hypoxia/genetics , Hypoxia/metabolism , Humans , Acclimatization/genetics , Transcription, Genetic , Single-Cell Analysis , Female , Multiomics
17.
Sensors (Basel) ; 24(9)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38732829

ABSTRACT

In 3D microsphere tracking, unlike in-plane motion that can be measured directly by a microscope, axial displacements are resolved by optical interference or a diffraction model. As a result, the axial results are affected by the environmental noise. The immunity to environmental noise increases with measurement accuracy and the signal-to-noise ratio (SNR). In compound digital holography microscopy (CDHM)-based measurements, precise identification of the tracking marker is critical to ensuring measurement precision. The reconstruction centering method (RCM) was proposed to suppress the drawbacks caused by installation errors and, at the same time, improve the correct identification of the tracking marker. The reconstructed center is considered to be the center of the microsphere, rather than the center of imaging in conventional digital holographic microscopy. This method was verified by simulation of rays tracing through microspheres and axial moving experiments. The axial displacements of silica microspheres with diameters of 5 µm and 10 µm were tested by CDHM in combination with the RCM. As a result, the SNR of the proposed method was improved by around 30%. In addition, the method was successfully applied to axial displacement measurements of overlapped microspheres with a resolution of 2 nm.

18.
Exp Neurol ; : 114841, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38821198

ABSTRACT

Alzheimer's disease (AD) is the most prevalent type of dementia, and its causes are currently diverse and not fully understood. In a previous study, we discovered that short-term treatment with miracle fruit seed (MFS) had a therapeutic effect on AD model mice, however, the precise mechanism behind this effect remains unclear. In this research, we aimed to establish the efficacy and safety of long-term use of MFS in AD model mice. A variety of cytokines and chemokines have been implicated in the development of AD. Previous studies have validated a correlation between the expression levels of C-X-C chemokine receptor type 4 (CXCR4) and disease severity in AD. In this research, we observed an upregulation of CXCR4 expression 1n hippocampal tissues in the AD model group, which was then reversed after MFS treatment. Moreover, CXCR4 knockout resulted in improved cognitive function in AD model mice, and MFS showed the ability to regulate CXCR4 expression. Finally, our findings indicate that CXCR4 knockout and long-term MFS treatment produce comparable effects in treating AD model mice. In conclusion, this research demonstrates that therapeutic efficacy and safety of long-term use in AD model mice. MFS treatment and the subsequent reduction of CXCR4 expression exhibit a neuroprotective role in the brain, highlighting their potential as therapeutic targets for AD.

19.
Article in English | MEDLINE | ID: mdl-38822119

ABSTRACT

The purpose of this study is to explore the potential molecular mechanism of Bidentis Bipinnatae Herba against gastric cancer by using network pharmacology methods, molecular docking, and cellular experimental validation. Medicinal plants related to gastric cancer were queried through TCMSP, SymMap, and Herb databases. The TCSMP database (drug-likeness ≥ 0.18) was used to retrieve the bioactive constituents. TCSMP, SwissTargetPrediction, and Herb databases were used to retrieve the target genes, and Cytoscape software was used to construct the "active ingredient-target" network. After protein interaction analysis using String 11.0 platform, the hub genes were screened using CytoHubba. The obtained hub genes were uploaded to the cBioPortal for pathway enrichment. The genes involved in gastric cancer-related RTK-RAS pathway were molecularly docked and experimentally validated. Bidentis Bipinnatae Herba was common to TCMSP, SymMap, and Herb databases. A total of nine active ingredients were obtained in Bidentis Bipinnatae Herba, acting on 192 targets. Seven hub genes were obtained from these target genes and enriched in the RTK-RAS pathway in gastric cancer. MAPK1 and EGFR had good molecular docking results with their corresponding chemicals. Cellular experiments showed that the treatment of luteolin, quercetin, and Okanin reduced the expression of EGFR in AGS cells; the treatment of luteolin and quercetin could reduce the expression of MAPK1. Bidentis Bipinnatae Herba contained active components, which may be anti-gastric cancer in a multi-target (MAPK1 and EGFR) manner.

20.
BMC Genomics ; 25(1): 539, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822248

ABSTRACT

Squamous promoter binding protein-like (SPL) genes encode plant-specific transcription factors (TFs) that play essential roles in modulating plant growth, development, and stress response. Pea (Pisum sativum L.) is a coarse grain crop of great importance in food production, biodiversity conservation and molecular genetic research, providing genetic information and nutritional resources for improving agricultural production and promoting human health. However, only limited researches on the structure and functions of SPL genes exist in pea (PsSPLs). In this study, we identified 22 PsSPLs and conducted a genome-wide analysis of their physical characteristics, chromosome distribution, gene structure, phylogenetic evolution and gene expression patterns. As a result, the PsSPLs were unevenly distributed on the seven chromosomes of pea and harbored the SBP domain, which is composed of approximately 76 amino acid residues. The phylogenetic analysis revealed that the PsSPLs clustered into eight subfamilies and showed high homology with SPL genes in soybean. Further analysis showed the presence of segmental duplications in the PsSPLs. The expression patterns of 22 PsSPLs at different tissues, developmental stages and under various stimulus conditions were evaluated by qRT-PCR method. It was found that the expression patterns of PsSPLs from the same subfamily were similar in different tissues, the transcripts of most PsSPLs reached the maximum peak value at 14 days after anthesis in the pod. Abiotic stresses can cause significantly up-regulated PsSPL19 expression with spatiotemporal specificity, in addition, four plant hormones can cause the up-regulated expression of most PsSPLs including PsSPL19 in a time-dependent manner. Therefore, PsSPL19 could be a key candidate gene for signal transduction during pea growth and development, pod formation, abiotic stress and plant hormone response. Our findings should provide insights for the elucidating of development regulation mechanism and breeding for resistance to abiotic stress pea.


Subject(s)
Gene Expression Regulation, Plant , Phylogeny , Pisum sativum , Plant Proteins , Stress, Physiological , Transcription Factors , Pisum sativum/genetics , Pisum sativum/growth & development , Stress, Physiological/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Genome, Plant , Multigene Family , Gene Expression Profiling , Chromosomes, Plant/genetics
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