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2.
Front Neurosci ; 18: 1410988, 2024.
Article in English | MEDLINE | ID: mdl-38988773

ABSTRACT

Objective: In this study, we used a bibliometric and visual analysis to evaluate the characteristics of the 100 most cited articles on axon regeneration. Methods: The 100 most cited papers on axon regeneration published between 2003 and 2023 were identified by searching the Web of Science Core Collection database. The extracted data included the title, author, keywords, journal, publication year, country, and institution. A bibliometric analysis was subsequently undertaken. Results: The examined set of 100 papers collectively accumulated a total of 39,548 citations. The number of citations for each of the top 100 articles ranged from 215 to 1,604, with a median value of 326. The author with the most contributions to this collection was He, Zhigang, having authored eight papers. Most articles originated in the United States (n = 72), while Harvard University was the institution with the most cited manuscripts (n = 19). Keyword analysis unveiled several research hotspots, such as chondroitin sulfate proteoglycan, alternative activation, exosome, Schwann cells, axonal protein synthesis, electrical stimulation, therapeutic factors, and remyelination. Examination of keywords in the articles indicated that the most recent prominent keyword was "local delivery." Conclusion: This study offers bibliometric insights into axon regeneration, underscoring that the United States is a prominent leader in this field. Our analysis highlights the growing relevance of local delivery systems in axon regeneration. Although these systems have shown promise in preclinical models, challenges associated with long-term optimization, agent selection, and clinical translation remain. Nevertheless, the continued development of local delivery technologies represents a promising pathway for achieving axon regeneration; however, additional research is essential to fully realize their potential and thereby enhance patient outcomes.

3.
J Agric Food Chem ; 72(28): 15971-15984, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38959404

ABSTRACT

Myristicin (MYR) mainly occurs in nutmeg and belongs to alkoxy-substituted allylbenzenes, a class of potentially toxic natural chemicals. RNA interaction with MYR metabolites in vitro and in vivo has been investigated in order to gain a better understanding of MYR toxicities. We detected two guanosine adducts (GA1 and GA2), two adenosine adducts (AA1 and AA2), and two cytosine adducts (CA1 and CA2) by LC-MS/MS analysis of total RNA extracts from cultured primary mouse hepatocytes and liver tissues of mice after exposure to MYR. An order of nucleoside adductions was found to be GAs > AAs > CAs, and the result of density functional theory calculations was in agreement with that detected by the LC-MS/MS-based approach. In vitro and in vivo studies have shown that MYR was oxidized by cytochrome P450 enzymes to 1'-hydroxyl and 3'-hydroxyl metabolites, which were then sulfated by sulfotransferases (SULTs) to form sulfate esters. The resulting sulfates would react with the nucleosides by SN1 and/or SN2 reactions, resulting in RNA adduction. The modification may alter the biochemical properties of RNA and disrupt RNA functions, perhaps partially contributing to the toxicities of MYR.


Subject(s)
Activation, Metabolic , Allylbenzene Derivatives , Cytochrome P-450 Enzyme System , RNA , Sulfotransferases , Tandem Mass Spectrometry , Animals , Mice , Sulfotransferases/metabolism , Sulfotransferases/genetics , Sulfotransferases/chemistry , Cytochrome P-450 Enzyme System/metabolism , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/chemistry , Allylbenzene Derivatives/chemistry , Allylbenzene Derivatives/metabolism , RNA/metabolism , RNA/chemistry , Male , Hepatocytes/metabolism , Dioxolanes/metabolism , Dioxolanes/chemistry , Dioxolanes/toxicity , Liver/metabolism , Liver/enzymology , Disulfides/chemistry , Disulfides/metabolism , Myristica/chemistry , Myristica/metabolism
4.
Cell Metab ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38959897

ABSTRACT

A mechanistic connection between aging and development is largely unexplored. Through profiling age-related chromatin and transcriptional changes across 22 murine cell types, analyzed alongside previous mouse and human organismal maturation datasets, we uncovered a transcription factor binding site (TFBS) signature common to both processes. Early-life candidate cis-regulatory elements (cCREs), progressively losing accessibility during maturation and aging, are enriched for cell-type identity TFBSs. Conversely, cCREs gaining accessibility throughout life have a lower abundance of cell identity TFBSs but elevated activator protein 1 (AP-1) levels. We implicate TF redistribution toward these AP-1 TFBS-rich cCREs, in synergy with mild downregulation of cell identity TFs, as driving early-life cCRE accessibility loss and altering developmental and metabolic gene expression. Such remodeling can be triggered by elevating AP-1 or depleting repressive H3K27me3. We propose that AP-1-linked chromatin opening drives organismal maturation by disrupting cell identity TFBS-rich cCREs, thereby reprogramming transcriptome and cell function, a mechanism hijacked in aging through ongoing chromatin opening.

5.
Biomed Chromatogr ; : e5953, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965739

ABSTRACT

In the search for pharmaceutically active compounds from natural products, it is crucial and challenging to develop separation or purification methods that target not only structurally similar compounds but also those with specific pharmaceutical functions. The adsorption-based method is widely employed in this field and holds potential for this application, given the diverse range of functional monomers that can be chosen based on structural or functional selectivity. In this work, an imidazolium ionic liquid (IL) modified paper membrane was synthesized via microwave reaction. Caffeic acid (CA), with potential interactions with imidazolium IL and a representative component of phenolic acids in Taraxaci Herba, was chosen as a target compound. After optimization of synthesis and extraction parameters, the resulting extraction membrane could be used to quantitatively analyze CA at ng/ml level, and to extract CA's analogues from the sample matrix. Cheminformatics confirmed the presence of structural and functional similarity among these extracted compounds. This study offers a novel approach to preparing a readily synthesized extraction membrane capable of isolating compounds with structural and functional analogies, as well as developing a membrane solid-phase extraction-based analytical method for natural products.

6.
Sci Rep ; 14(1): 15512, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38969766

ABSTRACT

This article is aimed at discussing the combined effect of mineral admixture and servicing temperature, especially in cold environment, on the properties of magnesium phosphate repair mortar (MPM). The influence mechanism of fly ash content on the microstructure and performance of MPM were firstly investigated, and then the evolution rules in properties of fly ash modified MPM cured at - 20 °C, 0 °C, 20 °C and 40 °C were further revealed. The results show that the incorporation of fly ash has no significant effect on the setting time and fluidity of MPM. When MPM is modified with 10 wt% and 15 wt% fly ash, its mechanical properties, adhesive strength, water resistance, and volume stability are effectively improved. Fly ash reduces the crystallinity and continuity of struvite enriched in hardened MPM, and its particles are embedded among struvite and unreacted MgO. The compressive strength of MPM-10 cured for various ages increases with the elevating of curing temperature, while the flexural strength, interfacial bonding strength, strength retention and linear shrinkage exhibits the opposite laws. When cured at 0 °C and - 20 °C, MPM-10 still has good early strength, water resistance and interfacial bonding properties, which indicates that MPM-10 provides with an ability of emergency repair of cracked components served in cold environments.

7.
Bioorg Chem ; 151: 107652, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39024804

ABSTRACT

DNA methyltransferases (DNMTs) play a crucial role in genomic DNA methylation. In mammals, DNMTs regulate the dynamic patterns of DNA methylation in embryonic and adult cells. Abnormal functions of DNMTs are often indicative of cancers, including overall hypomethylation and partial hypermethylation of tumor suppressor genes (TSG), which accelerate the malignancy of tumors, worsen the condition of patients, and significantly exacerbate the difficulty of cancer treatment. Currently, nucleoside DNMT inhibitors such as Azacytidine and Decitabine have been approved by the FDA and EMA for the treatment of acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), and myelodysplastic syndrome (MDS). Therefore, targeting DNMTs is a very promising anti-tumor strategy. This review mainly summarizes the therapeutic effects of DNMT inhibitors on cancers. It aims to provide more possibilities for the treatment of cancers by discovering more DNMT inhibitors with high activity, high selectivity, and good drug-like properties in the future.

8.
Adv Mater ; : e2405275, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38897213

ABSTRACT

The development of minimally invasive surgery has greatly advanced precision tumor surgery, but sometimes suffers from restricted visualization of the surgical field, especially during the removal of abdominal tumors. A 3-D inspection of tumors could be achieved by intravenously injecting tumor-selective fluorescent probes, whereas most of which are unable to instantly distinguish tumors via in situ spraying, which is urgently needed in the process of surgery in a convenient manner. In this study, we have designed an injectable and sprayable fluorescent nanoprobe, termed Poly-g-BAT, to realize rapid tumor imaging in freshly dissected human colorectal tumors and animal models. Mechanistically, the incorporation of γ-glutamyl group facilitates the rapid internalization of Poly-g-BAT, and these internalized nanoprobes can be subsequently activated by intracellular NAD(P)H: quinone oxidoreductase-1 to release near-infrared fluorophores. As a result, Poly-g-BAT can achieve a superior tumor-to-normal ratio (TNR) up to 12.3 and enable a fast visualization (3 min after in situ spraying) of tumor boundaries in the xenograft tumor models, Apcmin/+ mice models and fresh human tumor tissues. In addition, Poly-g-BAT is capable of identifying minimal premalignant lesions via intravenous injection. This article is protected by copyright. All rights reserved.

9.
J Cardiothorac Surg ; 19(1): 398, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937786

ABSTRACT

PURPOSE: Symptom assessment based on patient-reported outcome (PRO) can correlate with disease severity, making it a potential tool for threshold alerts of postoperative complications. This study aimed to determine whether shortness of breath (SOB) scores on the day of discharge could predict the development of post-discharge complications in patients who underwent lung cancer surgery. METHODS: Patients were from a study of a dynamic perioperative rehabilitation cohort of lung cancer patients focusing on patient-reported outcomes. Patients were assessed using the Perioperative Symptom Assessment Scale for Lung surgery (PSA-Lung). Logistic regression model was used to examine the potential association between SOB on the day of discharge and complications within 3 months after discharge. The post-discharge complications were taken as the anchor variable to determine the optimal cutpoint for SOB on the day of discharge. RESULTS: Complications within 3 months post-discharge occurred in 71 (10.84%) of 655 patients. Logistic regression analysis revealed that being female (OR 1.764, 95% CI 1.006-3.092, P < 0.05) and having two chest tubes (OR 2.026, 95% CI 1.107-3.710, P < 0.05) were significantly associated with post-discharge complications. Additionally, the SOB score on the day of discharge (OR 1.125, 95% CI 1.012-1.250, P < 0.05) was a significant predictor. The optimal SOB cutpoint was 5 (on a scale of 0-10). Patients with an SOB score ≥ 5 at discharge experienced a lower quality of life 1 month later compared to those with SOB score<5 at discharge (73 [50-86] vs. 81 [65-91], P < 0.05). CONCLUSION: SOB on the day of discharge may serve as an early warning sign for the timely detection of 3 month post-discharge complications.


Subject(s)
Dyspnea , Lung Neoplasms , Patient Discharge , Postoperative Complications , Humans , Female , Male , Lung Neoplasms/surgery , Dyspnea/etiology , Aged , Middle Aged , Pneumonectomy/adverse effects
10.
Nat Biotechnol ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38839873

ABSTRACT

Porphyrins and their derivatives find extensive applications in medicine, food, energy and materials. In this study, we produced porphyrin compounds by combining Rhodobacter sphaeroides as an efficient cell factory with enzymatic catalysis. Genome-wide CRISPRi-based screening in R. sphaeroides identifies hemN as a target for improved coproporphyrin III (CPIII) production, and exploiting phosphorylation of PrrA further improves the production of bioactive CPIII to 16.5 g L-1 by fed-batch fermentation. Subsequent screening and engineering high-activity metal chelatases and coproheme decarboxylase results in the synthesis of various metalloporphyrins, including heme and the anti-tumor agent zincphyrin. After pilot-scale fermentation (200 L) and setting up the purification process for CPIII (purity >95%), we scaled up the production of heme and zincphyrin through enzymatic catalysis in a 5-L bioreactor, with CPIII achieving respective enzyme conversion rates of 63% and 98% and yielding 10.8 g L-1 and 21.3 g L-1, respectively. Our strategy offers a solution for high-yield bioproduction of heme and other valuable porphyrins with substantial industrial and medical applications.

11.
Environ Health Perspect ; 132(6): 67008, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38889166

ABSTRACT

BACKGROUND: Accumulating evidence suggests that domestic water hardness is linked to health outcomes, but its association to all-cause and cause-specific cancers warrants investigation. OBJECTIVE: The aim of this study was to investigate the association of domestic hard water with all-cause and cause-specific cancers. METHODS: In the prospective cohort study, a total of 447,996 participants from UK Biobank who were free of cancer at baseline were included and followed up for 16 y. All-cause and 22 common cause-specific cancer diagnoses were ascertained using hospital inpatient records and self-reported data until 30 November 2022. Domestic water hardness, measured by CaCO3 concentrations, was obtained from the local water supply companies across England, Scotland, and Wales in 2005. Data were analyzed using Cox proportional hazard models, with adjustments for known measured confounders, including demographic, socioeconomic, clinical, biochemical, lifestyle, and environmental factors. RESULTS: Over a median follow-up of 13.6 y (range: 12.7-14.4 y), 58,028 all-cause cancer events were documented. A U-shaped relationship between domestic water hardness and all-cause cancers was observed (p for nonlinearity <0.001). In comparison with individuals exposed to soft water (0-60mg/L), the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause cancer were 1.00 (95% CI: 0.98, 1.02) for those exposed to moderate hard water (>60-120mg/L), 0.88 (95% CI: 0.84, 0.91) for those exposed to hard water (>120-180mg/L) and 1.06 (95% CI: 1.04, 1.08) for those exposed to very hard water (>180mg/L). Additionally, domestic water hardness was associated with 11 of 22 cause-specific cancers, including cancers of the esophagus, stomach, colorectal tract, lung, breast, prostate, and bladder, as well as non-Hodgkin lymphoma, multiple myeloma, malignant melanoma, and hematological malignancies. Moreover, we observed a positive linear relationship between water hardness and bladder cancer. DISCUSSION: Our findings suggest that domestic water hardness was associated with all-cause and multiple cause-specific cancers. Findings from the UK Biobank support a potentially beneficial association between hard water and the incidence of all-cause cancer. However, very hard water may increase the risk of all-cause cancer. https://doi.org/10.1289/EHP13606.


Subject(s)
Neoplasms , Humans , Neoplasms/epidemiology , Neoplasms/chemically induced , Prospective Studies , Male , Female , Middle Aged , United Kingdom/epidemiology , Aged , Water Supply/statistics & numerical data , Adult , Biological Specimen Banks , Proportional Hazards Models , Environmental Exposure/statistics & numerical data , UK Biobank
12.
Comput Methods Programs Biomed ; 254: 108284, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38924799

ABSTRACT

BACKGROUND: Coronary perfusion pressure (CPP) indicates spontaneous return of circulation and is recommended for high-quality cardiopulmonary resuscitation (CPR). This study aimed to investigate a method for non-invasive estimation of CPP using electrocardiography (ECG) and photoplethysmography (PPG) during CPR. METHODS: Nine pigs were used in this study. ECG, PPG, invasive arterial blood pressure (ABP), and right atrial pressure (RAP) signals were simultaneously recorded. The CPPs were estimated using three datasets: (a) ECG, (b) PPG, and (c) ECG and PPG, and were compared with invasively measured CPPs. Four machine-learning algorithms, namely support vector regression, random forest (RF), K-nearest neighbor, and gradient-boosted regression tree, were used for estimation of CPP. RESULTS: The RF model with a combined ECG and PPG dataset achieved better estimation of CPP than the other algorithms. Specifically, the mean absolute error was 4.49 mmHg, the root mean square error was 6.15 mm Hg, and the adjusted R2 was 0.75. A strong correlation was found between the non-invasive estimation and invasive measurement of CPP (r = 0.88), which supported our hypothesis that machine-learning-based analysis of ECG and PPG parameters can provide a non-invasive estimation of CPP for CPR. CONCLUSIONS: This study proposes a novel estimation of CPP using ECG and PPG with machine-learning-based algorithms. Non-invasively estimated CPP showed a high correlation with invasively measured CPP and may serve as an easy-to-use physiological indicator for high-quality CPR treatment.

13.
J Med Chem ; 67(13): 11326-11353, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38913763

ABSTRACT

BRD9 is a pivotal epigenetic factor involved in cancers and inflammatory diseases. Still, the limited selectivity and poor phenotypic activity of targeted agents make it an atypically undruggable target. PROTAC offers an alternative strategy for overcoming the issue. In this study, we explored diverse E3 ligase ligands for the contribution of BRD9 PROTAC degradation. Through molecular docking, binding affinity analysis, and structure-activity relationship study, we identified a highly potent PROTAC E5, with excellent BRD9 degradation (DC50 = 16 pM) and antiproliferation in MV4-11 cells (IC50 = 0.27 nM) and OCI-LY10 cells (IC50 = 1.04 nM). E5 can selectively degrade BRD9 and induce cell cycle arrest and apoptosis. Moreover, the therapeutic efficacy of E5 was confirmed in xenograft tumor models, accompanied by further RNA-seq analysis. Therefore, these results may pave the way and provide the reference for the discovery and investigation of highly effective PROTAC degraders.


Subject(s)
Antineoplastic Agents , Cell Proliferation , Molecular Docking Simulation , Ubiquitin-Protein Ligases , Humans , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Structure-Activity Relationship , Cell Proliferation/drug effects , Ubiquitin-Protein Ligases/metabolism , Cell Line, Tumor , Mice , Drug Discovery , Hematologic Neoplasms/drug therapy , Hematologic Neoplasms/pathology , Hematologic Neoplasms/metabolism , Transcription Factors/metabolism , Transcription Factors/antagonists & inhibitors , Apoptosis/drug effects , Proteolysis/drug effects , Mice, Nude , Mice, Inbred BALB C , Xenograft Model Antitumor Assays , Drug Screening Assays, Antitumor , Bromodomain Containing Proteins
14.
Drug Metab Dispos ; 52(8): 911-918, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38849209

ABSTRACT

Arsenite is an important heavy metal. Some Chinese traditional medicines contain significant amounts of arsenite. The aim of this study was to investigate subacute exposure of arsenite on activities of cytochrome P450 enzymes and pharmacokinetic behaviors of drugs in rats. Midazolam, tolbutamide, metoprolol, omeprazole, caffeine, and chlorzoxazone, the probe substrates for cytochrome P450 (CYP) s3A, 2C6, 2D, 2C11, 1A, and 2E, were selected as probe drugs for the pharmacokinetic study. Significant decreases in areas under the curves of probe substrates were observed in rats after consecutive 30-day exposure to As at 12 mg/kg. Microsomal incubation study showed that the subacute exposure to arsenite resulted in little change in effects on the activities of P450 enzymes examined. However, everted gut sac study demonstrated that such exposure induced significant decreases in intestinal absorption of these drugs by both passive diffusion and carrier-mediated transport. In addition, in vivo study showed that the arsenite exposure decreased the rate of peristaltic propulsion. The decreases in intestinal permeability of the probe drugs and peristaltic propulsion rate most likely resulted in the observed decreases in the internal exposure of the probe drugs. Exposure to arsenite may lead to the reduction of the efficiencies of pharmaceutical agents coadministered resulting from the observed drug-drug interactions. SIGNIFICANCE STATEMENT: Exposure to arsenite may lead to the reduction of the efficiencies of pharmaceutical agents coadministered resulting from the observed drug-drug interactions. The present study, we found that P450 enzyme probe drug exposure was reduced in arsenic-exposed animals (areas under the curve) and the intestinal absorption of the drug was reduced in the animals. Subacute arsenic exposure tends to cause damage to intestinal function, which leads to reduced drug absorption.


Subject(s)
Arsenites , Cytochrome P-450 Enzyme System , Drug Interactions , Rats, Sprague-Dawley , Animals , Arsenites/toxicity , Arsenites/pharmacokinetics , Male , Rats , Cytochrome P-450 Enzyme System/metabolism , Intestinal Absorption/drug effects , Microsomes, Liver/drug effects , Microsomes, Liver/metabolism , Omeprazole/pharmacology , Omeprazole/pharmacokinetics , Midazolam/pharmacokinetics , Caffeine/pharmacokinetics , Chlorzoxazone/pharmacokinetics , Metoprolol/pharmacokinetics , Metoprolol/pharmacology , Tolbutamide/pharmacokinetics , Sodium Compounds/toxicity , Sodium Compounds/pharmacokinetics
15.
Orthop Surg ; 16(7): 1744-1750, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38828747

ABSTRACT

BACKGROUND: Surgical treatment for hinge failure in mega-prosthesis continues to be a challenge. This study introduces a new method for treating hinge failure by using a unilateral prosthesis and hinge revision. CASE PRESENTATION: We here present two patients who underwent mega-prosthesis reconstruction after resection of osteosarcoma in the distal femur. To address the issue of knee hyperextension after mega-prosthesis reconstruction, one patient underwent three revision surgeries, two surgeries were performed using the original hinge, and one surgery involved a newly designed hinge. To resolve the problem of dislocation, one patient underwent three revisions, with the first two revisions not involving hinge replacement and the third revision involving a newly designed hinge. Two replacements of unilateral prosthesis and hinge renovations were successful. CONCLUSIONS: Unilateral prosthesis and newly designed hinge device revision are effective in treating the failure of old-fashioned mega-prosthesis hinges.


Subject(s)
Osteosarcoma , Prosthesis Design , Prosthesis Failure , Reoperation , Humans , Male , Osteosarcoma/surgery , Female , Knee Prosthesis , Arthroplasty, Replacement, Knee/instrumentation , Arthroplasty, Replacement, Knee/methods , Femoral Neoplasms/surgery , Adult
16.
Int Immunopharmacol ; 137: 112498, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-38908079

ABSTRACT

The neuroinflammatory response triggered by cerebral ischemia-reperfusion injury (CIRI) is characterized by the upsurge of pro-inflammatory cytokines, including TNF-α, IL-1ß, and IL-6, which promote leukocyte infiltration and subsequent accumulation in the ischemic zone. This accumulation further intensifies inflammation and aggravates ischemic damage. Certolizumab pegol (CZP), a monoclonal antibody targeting TNF-α, is widely used in treating various inflammatory diseases. This study explored the therapeutic potential of CZP in a mouse model of CIRI, induced by middle cerebral artery occlusion (MCAO), focusing on its influence on the microglial inflammatory response. In vitro analyses revealed that CZP markedly inhibits TNF-α-stimulated inflammation in primary microglia with an EC50 of 1.743 ng/mL. In vivo, MCAO mice treated with CZP (10 µg/mouse, i.p.) for 3 days showed reduced infarct volume, partially improved neurological function, and diminished blood-brain barrierdisruption. Additionally, CZP treatment curtailed microglial activation and the release of pro-inflammatory mediators in the early stages of stroke. It also favorably modulated microglial M1/M2 polarization, rebalanced Th17/Treg cells dynamics, and inhibited Caspase-8-mediated GSDMD cleavage, preventing microglial pyroptosis. Collectively, this study described that the treatment with CZP reversed damaging process caused by CIRI, offering a promising therapeutic strategy for the treatment of ischemic stroke.


Subject(s)
Certolizumab Pegol , Infarction, Middle Cerebral Artery , Mice, Inbred C57BL , Microglia , Reperfusion Injury , Tumor Necrosis Factor-alpha , Animals , Reperfusion Injury/drug therapy , Certolizumab Pegol/therapeutic use , Certolizumab Pegol/pharmacology , Male , Mice , Microglia/drug effects , Tumor Necrosis Factor-alpha/metabolism , Infarction, Middle Cerebral Artery/drug therapy , Disease Models, Animal , Brain Ischemia/drug therapy , Cells, Cultured , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Humans , Brain/drug effects , Brain/pathology , Brain/metabolism , Cytokines/metabolism
17.
Apoptosis ; 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38853201

ABSTRACT

This study delivers a thorough analysis of long non-coding RNAs (lncRNAs) in regulating programmed cell death (PCD), vital for neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD). We propose a new framework PCDLnc, and identified 20 significant lncRNAs, including HEIH, SNHG15, and SNHG5, associated with PCD gene sets, which were known for roles in proliferation and apoptosis in neurodegenerative diseases. By using GREAT software, we identified regulatory functions of top lncRNAs in different neurodegenerative diseases. Moreover, lncRNAs cis-regulated mRNAs linked to neurodegeneration, including JAK2, AKT1, EGFR, CDC42, SNCA, and ADIPOQ, highlighting their therapeutic potential in neurodegenerative diseases. A further exploration into the differential expression of mRNA identified by PCDLnc revealed a role in apoptosis, ferroptosis and autophagy. Additionally, protein-protein interaction (PPI) network analysis exposed abnormal interactions among key genes, despite their consistent expression levels between disease and normal samples. The randomforest model effectively distinguished between disease samples, indicating a high level of accuracy. Shared gene subsets in AD and PD might serve as potential biomarkers, along with disease-specific gene sets. Besides, we also found the strong relationship between AD and immune infiltration. This research highlights the role of lncRNAs and their associated genes in PCD in neurodegenerative diseases, offering potential therapeutic targets and diagnostic markers for future study and clinical application.

18.
Nanomedicine ; 60: 102757, 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38889854

ABSTRACT

Surgical site infection (SSI) significantly affects patient recovery time, health outcomes and quality of life which is closely associated with the use of implants or mesh. Sutures are the most frequently used implants that play a significant role in the development of SSI. Studies have demonstrated that the administration of effective bactericidal and anti-inflammatory treatments can significantly decrease the incidence of SSI. To address this concern, a versatile suture was engineered by coating MoO3-X nanodots in this study. The incorporation of MoO3-X nanodots endowed the suture with desirable antibacterial and anti-inflammatory properties that were evaluated in in vitro and in vivo experiments. The results showed its remarkable ability to facilitate wound healing and prevent SSI through its dual action of combating bacterial infection and reducing inflammation. These findings highlight the promising potential of this multifunctional surgical suture as a versatile tool to promote better outcomes in surgical procedures.

19.
Food Sci Nutr ; 12(6): 4435-4442, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38873477

ABSTRACT

4-Hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF) is a flavor compound widely found in natural products and is used in food as a flavor-enhancing agent. Quinone oxidoreductase (QOR) was verified as a key enzyme to synthesize HDMF in strawberry, while its impact on HDMF production by Zygosaccharomyces rouxii was still unknown. The QOR gene was cloned and overexpressed in Z. rouxii, and its impact on HDMF production by Z. rouxii was then further analyzed. At the same time, it is expected to obtain engineered strains of Z. rouxii with high HDMF production. The results showed that the engineered strains of Z. rouxii exhibit different levels of QOR gene expression and HDMF production; among them, the QOR6 strain exhibiting the highest gene expression level and HDMF production was named as ZrQOR. The HDMF production of the ZrQOR strain was significantly higher than that of wild-type Z. rouxii at 3 and 5 days of culture, with 1.41-fold and 1.08-fold increases, respectively. At 3 days of fermentation, the highest HDMF yield of ZrQOR strain was obtained (2.75 mg/L), 2 days ahead of the reported highest HDMF production by Z. rouxii. At 3, 5, and 7 days, QOR gene expression was 4.8-fold, 3.3-fold, and 5.6-fold higher in the ZrQOR strain than in the wild-type Z. rouxii, respectively. Therefore, overexpression of the QOR gene facilitates HDMF synthesis. The genetic stability of the 0-20 generation ZrQOR strain was stable, and there was no significant difference in colony shape, QOR expression, or HDMF production compared to the wild type. In this study, the genetic engineering Z. rouxii strain was used to improve HDMF production. This research has laid the groundwork for further industrial production of HDMF via microbial synthesis.

20.
Clin Oral Investig ; 28(7): 375, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38878120

ABSTRACT

OBJECTIVE: To investigate the impact of mineralized dentin matrix (MDM) on the prognosis on bone regeneration and migration of retained roots after coronectomy. MATERIALS AND METHODS: Patients were divided into three groups based on the type of bone graft after coronectomy: Group C (n = 20, collagen), Group T (n = 20, tricalcium phosphate (TCP) + collagen), and Group D (n = 20, MDM + collagen). CBCT scans, conducted immediately and 6 months after surgery, were analyzed using digital software. Primary outcomes, including changes in bone defect depth and retained root migration distance, were evaluated 6 months after surgery. RESULTS: After 6 months, both Groups D and T exhibited greater reduction of the bone defect and lesser retained root migration than Group C (p < 0.001). Group D had greater regenerated bone volume in the distal 2 mm (73 mm3 vs. 57 mm3, p = 0.011) and lesser root migration (2.18 mm vs. 2.96 mm, p < 0.001) than Group T. The proportion of completely bone embedded retained roots was also greater in Group D than in Group C (70.0% vs. 42.1%, p = 0.003). CONCLUSIONS: MDM is an appropriate graft material for improving bone defect healing and reducing retained root migration after coronectomy. CLINICAL RELEVANCE: MDM is an autogenous material prepared chairside, which can significantly improve bone healing and reduce the risk of retained root re-eruption. MDM holds promise as a routine bone substitute material after M3M coronectomy.


Subject(s)
Bone Regeneration , Calcium Phosphates , Collagen , Cone-Beam Computed Tomography , Dentin , Humans , Male , Female , Calcium Phosphates/therapeutic use , Prognosis , Middle Aged , Collagen/therapeutic use , Bone Regeneration/drug effects , Tooth Root/diagnostic imaging , Tooth Root/surgery , Adult , Tooth Crown/surgery , Treatment Outcome , Bone Transplantation/methods , Bone Substitutes/therapeutic use
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