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1.
Brain Connect ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623770

RESUMO

PURPOSE: Persistent postural-perception dizziness (PPPD) is a chronic subjective form of dizziness characterized by the exacerbation of dizziness with active or passive movement, complex visual stimuli, and upright posture. Therefore, we aimed to analyze the resting-state functional magnetic resonance imaging (fMRI) in patients with PPPD using fractional amplitude of low-frequency fluctuation (fALFF) and voxel-mirrored homotopic connectivity (VMHC) and evaluate the correlation between abnormal regions in the brain and clinical features to investigate the pathogenesis of PPPD. METHODS: Thirty patients with PPPD (19 females and 11 males) and 30 healthy controls (HC) (18 females and 12 males) were closely matched for age and sex. The fALFF and VMHC methods were used to investigate differences in fMRI (BOLD sequences) between the PPPD and HC groups and to explore the associations between areas of functional abnormality and clinical characteristics (Dizziness, Anxiety, Depression, and Duration). RESULT: Compared to the HC group, patients with PPPD displayed different functional change patterns, with increased fALFF in the right precuneus and decreased VMHC in the bilateral precuneus. Additionally, patients with PPPD had a positive correlation between precuneus fALFF values and dizziness handicap inventory (DHI) scores, and a negative correlation between VMHC values and the disease duration. CONCLUSIONS: Precuneus dysfunction was observed in patients with PPPD. The fALFF values correlated with the degree of dizziness in PPPD, and changes in VMHC values were associated with the duration of dizziness, suggesting that fMRI changes in the precuneus of patients could be used as a potential imaging marker for PPPD.

2.
Phytomedicine ; 129: 155592, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38608597

RESUMO

BACKGROUND: Vascular smooth muscle cell (VSMC) proliferation and phenotypic switching are key mechanisms in the development of proliferative arterial diseases. Notably, reprogramming of the glucose metabolism pattern in VSMCs plays an important role in this process. PURPOSE: The aim of this study is to investigate the therapeutic potential and the mechanism underlying the effect of bergenin, an active compound found in Bergenia, in proliferative arterial diseases. METHODS: The effect of bergenin on proliferative arterial disease was evaluated using platelet-derived growth factor (PDGF)-stimulated VSMCs and a mouse model of carotid artery ligation. VSMC proliferation and phenotypic switching were evaluated in vitro using cell counting kit-8, 5-ethynyl-2-deoxyuridine incorporation, scratch, and transwell assays. Carotid artery neointimal hyperplasia was evaluated in vivo using hematoxylin and eosin staining and immunofluorescence. The expression of proliferation and VSMC contractile phenotype markers was evaluated using PCR and western blotting. RESULTS: Bergenin treatment inhibited PDGF-induced VSMC proliferation and phenotypic switching and reduced neointimal hyperplasia in the carotid artery ligation model. Additionally, bergenin partially reversed the PDGF-induced Warburg-like glucose metabolism pattern in VSMCs. RNA-sequencing data revealed that bergenin treatment significantly upregulated Ndufs2, an essential subunit of mitochondrial complex I. Ndufs2 knockdown attenuated the inhibitory effect of bergenin on PDGF-induced VSMC proliferation and phenotypic switching, and suppressed neointimal hyperplasia in vivo. Conversely, Ndufs2 overexpression enhanced the protective effect of bergenin. Moreover, Ndufs2 knockdown abrogated the effects of bergenin on the regulation of glucose metabolism in VSMCs. CONCLUSION: These findings suggest that bergenin is effective in alleviating proliferative arterial diseases. The reversal of the Warburg-like glucose metabolism pattern in VSMCs during proliferation and phenotypic switching may underlie this therapeutic mechanism.

4.
FASEB J ; 38(7): e23589, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38572594

RESUMO

Breast cancer antiestrogen resistance 4 (BCAR4) has been suggested that can modulate cell behavior, resulting in tumorigenesis and chemoresistance. However, the underlying mechanisms of BCAR4 in trastuzumab resistance (TR) is still elusive. Here, we explored the function and the underlying mechanism of BCAR4 involving in TR. We found that BCAR4 is significantly upregulated in trastuzumab-resistant BC cells. Knockdown of BCAR4 could sensitize the BC cells to trastuzumab and suppress epithelial-mesenchymal transition (EMT). Mechanically, BCAR4 promotes yes-associated protein 1 (YAP1) expression by competitively sponging miR-665, to activated TGF-ß signaling. Reciprocally, YAP1 could occupy the BCAR4 promoter to enhance its transcription, suggesting that there exists a positive feedback regulation between YAP1 and BCAR4. Targeting the BCAR4/miR-665/YAP1 axis may provide a novel insight of therapeutic approaches for TR in BC.


Assuntos
Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Humanos , Feminino , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , MicroRNAs/metabolismo , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica
5.
Hum Mol Genet ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557732

RESUMO

Lowe syndrome, a rare X-linked multisystem disorder presenting with major abnormalities in the eyes, kidneys, and central nervous system, is caused by mutations in OCRL gene (NG_008638.1). Encoding an inositol polyphosphate 5-phosphatase, OCRL catalyzes the hydrolysis of PI(4,5)P2 into PI4P. There are no effective targeted treatments for Lowe syndrome. Here, we demonstrate a novel gene therapy for Lowe syndrome in patient fibroblasts using an adenine base editor (ABE) that can efficiently correct pathogenic point mutations. We show that ABE8e-NG-based correction of a disease-causing mutation in a Lowe patient-derived fibroblast line containing R844X mutation in OCRL gene, restores OCRL expression at mRNA and protein levels. It also restores cellular abnormalities that are hallmarks of OCRL dysfunction, including defects in ciliogenesis, microtubule anchoring, α-actinin distribution, and F-actin network. The study indicates that ABE-mediated gene therapy is a feasible treatment for Lowe syndrome, laying the foundation for therapeutic application of ABE in the currently incurable disease.

6.
Appl Opt ; 63(8): 1947-1951, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38568633

RESUMO

Three samples whose growth temperatures were 450°C, 500°C, and 560°C for S E S A M 1, S E S A M 2, and S E S A M 3, respectively, were tested by femto-second time-resolved transient absorption spectroscopy. The results indicate that the carrier dynamics of excited state absorption were dominant, and the lifetimes of carriers trapped by defect levels were about tens of pico-seconds. To further study the influence of carrier dynamics and recovery time of samples by ion-implantation, B + ions of 80 and 130 KeV were implanted into the samples with dose of 1014/c m 2. The modified samples showed a dominance of ultra-fast carrier dynamics of ground-state bleaching and direct recombination, which lasted for hundreds of femto-seconds, over excited state absorption. Additionally, carrier fast trapping was observed to be competitive with the excited state absorption process. After ion-implantation, the carrier dynamics of carrier trapping were enhanced, which contributed to forming an ultra-short laser, while the carrier dynamics of absorption of the excited state were suppressed. The conclusion that defect levels were partially eliminated by B + ion-implantation can be drawn.

7.
Br J Ophthalmol ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38604620

RESUMO

AIMS: The aim of this study was to analyse the effective lens position (ELP) in patients with Marfan syndrome (MFS) and ectopia lentis (EL). METHODS: Patients with MFS undergoing lens removal and primary intraocular lens (IOL) implantation were enrolled in the study. The back-calculated ELP was obtained with the vergence formula and compared with the theoretical ELPs. The back-calculated ELP and ELP error were evaluated among demographic and biometric parameters, including axial length (AL), corneal curvature radius (CCR) and white-to-white (WTW). RESULTS: A total of 292 eyes from 200 patients were included. The back-calculated ELP was lower in patients undergoing scleral-fixated IOL than those receiving in-the-bag IOL implantation (4.54 (IQR 3.65-5.20) mm vs 4.98 (IQR 4.56-5.67) mm, p<0.001). The theoretical ELP of the SRK/T formula exhibited the highest accuracy, with no difference from the back-calculated ELP in patients undergoing in-the-bag IOL implantation (5.11 (IQR 4.83-5.65) mm vs 4.98 (IQR 4.56-5.67) mm, p=0.209). The ELP errors demonstrated significant correlations with refraction prediction error (PE): a 1 mm ELP error led to PE of 2.42D (AL<22 mm), 1.47D (22 mm≤AL<26 mm) and 0.54D (AL≥26 mm). Multivariate analysis revealed significant correlations of ELP with AL (b=0.43, p<0.001), CCR (b=-0.85, p<0.001) and WTW (b=0.41, p=0.004). CONCLUSION: This study provides novel insights into the origin of PE in patients with MFS and EL and potentially refines existing formulas.

8.
J Surg Oncol ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38606525

RESUMO

BACKGROUND: Retroperitoneal partial nephrectomy (RLPN) is the premier treatment for localized renal tumors despite narrow operation space. Many efforts have been taken to facilitate the operation of RLPN, but the optimal resolution remains debatable. OBJECTIVE: To explore the feasibility of using Mini-lap to improve workspace and surgical vision in RLPN. DESIGN, SETTING, AND PARTICIPANTS: A multicenter retrospective review of 51 patients who underwent RLPN with Mini-lap from January 2018 to December 2020 was conducted. SURGICAL PROCEDURE: Standard RLPN under three poles was performed in all cases. We highlighted the usage of Mini-lap (Teleflex Minilap percutaneous Surgical System) as a novel retractor in RLPN. OUTCOME AND MEASUREMENTS AND STATICAL ANALYSIS: Demographics, preoperative, intraoperative, and postoperative outcomes were assessed. RESULTS AND LIMITATIONS: All 51 cases completed RLPN with three ports successfully and no conversion to open surgery. The mean diameter of tumors was (3.53 ± 1.05) cm, in which 62.7% (32/51) were located anteriorly. The operation time and warm ischemic time (WIT) were (86.7 ± 15.9) min and (25.6 ± 5) min respectively. Minor complications (Clavien grade 1-2) occurred in 6 cases. The limitations were small sample size, retrospective design, and absence of control. CONCLUSIONS: Mini-lap could be used as a mini-retractor in RLPN, sparing extra assistant ports, expanding workspace, and optimizing vision. PATIENT SUMMARY: With highlights of larger workspace and less instrument interference, mini-lap could be applied in retroperitoneal laparoscopic partial nephrectomy.

9.
Adv Healthc Mater ; : e2304488, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38588047

RESUMO

Transcatheter arterial chemoembolization (TACE) has proven effective in blocking tumor-supplied arteries and delivering localized chemotherapeutic treatment to combat tumors. However, traditional embolic TACE agents exhibit certain limitations, including insufficient chemotherapeutic drug-loading and sustained-release capabilities, non-biodegradability, susceptibility to aggregation, and unstable mechanical properties. This study introduces a novel approach to address these shortcomings by utilizing a complex coacervate as a liquid embolic agent for tumor chemoembolization. By mixing oppositely charged quaternized chitosan (QCS) and gum arabic (GA), a QCS/GA polymer complex coacervate with shear-thinning property is obtained. Furthermore, the incorporation of the contrast agent Iohexol (I) and the chemotherapeutic doxorubicin (DOX) into the coacervate leads to the development of an X-ray-opaque QCS/GA/I/DOX coacervate embolic agent capable of carrying drugs. This innovative formulation effectively embolizes the renal arteries without recanalization. More importantly, the QCS/GA/I/DOX coacervate can successfully embolize the supplying arteries of the VX2 tumors in rabbit ear and liver. Coacervates can locally release DOX to enhance its therapeutic effects, resulting in excellent antitumor efficacy. This coacervate embolic agent exhibits substantial potential for tumor chemoembolization due to its shear-thinning performance, excellent drug-loading and sustained-release capabilities, good biocompatibility, thrombogenicity, biodegradability, safe and effective embolic performance, and user-friendly application.

10.
Ageing Res Rev ; 96: 102286, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38561044

RESUMO

Chemokines and their corresponding receptors play crucial roles in orchestrating inflammatory and immune responses, particularly in the context of pathological conditions disrupting the internal environment. Among these receptors, CCR5 has garnered considerable attention due to its significant involvement in the inflammatory cascade, serving as a pivotal mediator of neuroinflammation and other inflammatory pathways associated with various diseases. However, a notable gap persists in comprehending the intricate mechanisms governing the interplay between CCR5 and its ligands across diverse and intricate inflammatory pathologies. Further exploration is warranted, especially concerning the inflammatory cascade instigated by immune cell infiltration and the precise binding sites within signaling pathways. This study aims to illuminate the regulatory axes modulating signaling pathways in inflammatory cells by providing a comprehensive overview of the pathogenic processes associated with CCR5 and its ligands across various disorders. The primary focus lies on investigating the pathomechanisms associated with CCR5 in disorders related to neuroinflammation, alongside the potential impact of aging on these processes and therapeutic interventions. The discourse culminates in addressing current challenges and envisaging potential future applications, advocating for innovative research endeavors to advance our comprehension of this realm.


Assuntos
Doenças Neuroinflamatórias , Receptores CCR5 , Humanos , Receptores CCR5/metabolismo , Transdução de Sinais
11.
bioRxiv ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617277

RESUMO

Optineurin (OPTN) mutations are linked to amyotrophic lateral sclerosis (ALS) and normal tension glaucoma (NTG), but a relevant animal model is lacking, and the molecular mechanisms underlying neurodegeneration are unknown. We found that OPTN C-terminus truncation (OPTN∆C) causes late-onset neurodegeneration of retinal ganglion cells (RGCs), optic nerve (ON), and spinal cord motor neurons, preceded by a striking decrease of axonal mitochondria. Surprisingly, we discover that OPTN directly interacts with both microtubules and the mitochondrial transport complex TRAK1/KIF5B, stabilizing them for proper anterograde axonal mitochondrial transport, in a C-terminus dependent manner. Encouragingly, overexpressing OPTN/TRAK1/KIF5B reverses not only OPTN truncation-induced, but also ocular hypertension-induced neurodegeneration, and promotes striking ON regeneration. Therefore, in addition to generating new animal models for NTG and ALS, our results establish OPTN as a novel facilitator of the microtubule-dependent mitochondrial transport necessary for adequate axonal mitochondria delivery, and its loss as the likely molecular mechanism of neurodegeneration.

12.
Free Radic Biol Med ; 219: 64-75, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38604314

RESUMO

Cardiovascular diseases (CVDs) are the leading cause of death globally, resulting in a major health burden. Thus, an urgent need exists for exploring effective therapeutic targets to block progression of CVDs and improve patient prognoses. Immune and inflammatory responses are involved in the development of atherosclerosis, ischemic myocardial damage responses and repair, calcification, and stenosis of the aortic valve. These responses can involve both large and small blood vessels throughout the body, leading to increased blood pressure and end-organ damage. While exploring potential avenues for therapeutic intervention in CVDs, researchers have begun to focus on immune metabolism, where metabolic changes that occur in immune cells in response to exogenous or endogenous stimuli can influence immune cell effector responses and local immune signaling. Itaconate, an intermediate metabolite of the tricarboxylic acid (TCA) cycle, is related to pathophysiological processes, including cellular metabolism, oxidative stress, and inflammatory immune responses. The expression of immune response gene 1 (IRG1) is upregulated in activated macrophages, and this gene encodes an enzyme that catalyzes the production of itaconate from the TCA cycle intermediate, cis-aconitate. Itaconate and its derivatives have exerted cardioprotective effects through immune modulation in various disease models, such as ischemic heart disease, valvular heart disease, vascular disease, heart transplantation, and chemotherapy drug-induced cardiotoxicity, implying their therapeutic potential in CVDs. In this review, we delve into the associated signaling pathways through which itaconate exerts immunomodulatory effects, summarize its specific roles in CVDs, and explore emerging immunological therapeutic strategies for managing CVDs.

13.
Front Bioeng Biotechnol ; 12: 1362110, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38600950

RESUMO

Background: Previous studies have shown that the lateral femoral condyle ratio (LFCR) measured by X-ray has a significant relationship with the anterior cruciate ligament (ACL) injury. However, few relevant studies have been performed on LFCR measured by magnetic resonance imaging (MRI). Purpose: (1) To evaluate the relationship between LFCR measured by MRI and ACL injury or rerupture. (2) To compare the LFCR measured by MRI with existing bony morphological risk factors and screen out the most predictive risk factors for primary ACL injury or rerupture. Study Design: Cohort study; Level of evidence, 3. Methods: Totally 147 patients who underwent knee arthroscopic surgery from 2015 to 2019 with minimum follow-up of 48 months were retrospectively evaluated. Patients were placed into three groups: 1) the control group of patients with simple meniscus tears without ligament injury; 2) the primary noncontact ACL injury group; 3) ACL rerupture group (ACL reconstruction failure). The LFCR measured by MRI and other previous known risk factors associated with MRI (notch width index, medial tibial slope, lateral tibial slope, medial tibial depth, lateral tibial height) were performed to evaluate their predictive value for ACL injury and rerupture. All the risk factors with p < 0.01 according to univariate analysis were included in the logistic regression models. Receiver operating characteristic (ROC) curves were analyzed for sensitivity, specificity, cut-off, and area under the curve (AUC). Z tests were used to compare the AUC values. Results: The LFCR measured by MRI was obviously higher in primary ACL injury group (0.628 ± 0.020) and in ACL rerupture group (0.625 ± 0.021) than that in the control group (0.593 ± 0.030). The best risk factor was the LFCR with a cut-off of 0.602 (AUC, 0.818; 95% CI, 0.748-0.878; sensitivity, 90%; specificity, 66%). When combined with lateral tibial slope (cutoff, 7°) and lateral tibial height (cutoff, 3.6 mm), the diagnostic performance was improved significantly (AUC, 0.896; 95% CI, 0.890-0.950; sensitivity, 87%; specificity, 80%). Conclusion: The increased LFCR measured by MRI was associated with a significantly higher risk for ACL injury or rerupture. The combination of LFCR, lateral tibial slope and lateral tibial height were the most predictive risk factors. This may help clinicians identify susceptible individuals and allow precision approaches for better prevention, treatment and management of this disease.

14.
Discov Oncol ; 15(1): 103, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573423

RESUMO

BACKGROUND: Soft tissue recurrence of giant cell tumor of bone (GCTB) is rare. This study aims to provide its prevalence, recurrent locations, risk factors, effective detection methods and a modified classification for this recurrence. METHODS: Patients with soft tissue recurrence after primary surgery for GCTB were screened from January 2003 to December 2022. General data, recurrence frequency, types according to an original classification (type-I: peripheral ossification; type-II: central ossification; type-III: without ossification), a modified classification with more detailed subtypes (type I-1: ≤ 1/2 peripheral ossification; type I-2: ≥ 1/2 peripheral ossification; type II-1: ≤ 1/2 central ossification; type II-2: ≥ 1/2 central ossification; type III: without ossification), locations, detection methods such as ultrasonography, X-ray, CT or MRI, Musculoskeletal Tumor Society (MSTS) scores were recorded. Multivariate regression analysis was conducted to identify risk factors for recurrence frequency. RESULTS: A total of 558 recurrent cases were identified from 2009 patients with GCTB. Among them, 32 were soft tissue recurrence. The total recurrence rate was 27.78% (558/2009). Soft tissue recurrence rate was 5.73% among 558 recurrent cases, and 1.59% among 2009 GCTB patients, respectively. After excluding one patient lost to follow-up, 10 males and 21 females with the mean age of 28.52 ± 9.93 (16-57) years were included. The definitive diagnosis of all recurrences was confirmed by postoperative pathology. The interval from primary surgery to the first recurrence was 23.23 ± 26.12 (2-27) months. Eight recurrences occurred from primary GCTB located at distal radius, followed by distal femur (6 cases). Recurrence occurred twice in 12 patients and 3 times in 7 patients. Twenty-seven recurrences were firstly detected by ultrasonography, followed by CT or X-ray (10 cases in each). Types at the first recurrence were 5 cases in type-I, 8 in type-II and 18 in type-III. According to the modified classification, 3 patients in type I-1, 2 in type I-2, 1 in type II-1, 7 in type II-2, and 18 in type III. The mean MSTS score was 26.62 ± 4.21 (14-30). Neither Campanacci grade nor recurrence type, modified classification and other characters, were identified as risk factors. CONCLUSIONS: Soft tissue recurrence of GCTB may recur for more than once and distal radius was the most common location of primary GCTB that would suffer a soft tissue recurrence. Ultrasonography was a useful method to detect the recurrence. Since no risk factors were discovered, a careful follow-up with ultrasonography was recommended.

15.
Adv Sci (Weinh) ; : e2309760, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582506

RESUMO

The treatment of tumors in developing countries, especially those with poor medical conditions, remains a significant challenge. Herein, a novel solvent-exchange strategy to prepare adhesive hydrogels for the concurrent treatment of tumors through synchronous ethanol ablation and local chemotherapy is reported. First, a poly (gallic acid-lipoic acid) (PGL) ethanol gel is prepared that can undergo solvent exchange with water to form a hydrogel in situ. PGL ethanol gel deposited on the wet tissue can form a hydrogel in situ to effectively repel interfacial water and establish a tight contact between the hydrogel and tissue. Additionally, the functional groups between the hydrogels and tissues can form covalent and non-covalent bonds, resulting in robust adhesion. Furthermore, this PGL ethanol gel demonstrates exceptional capacity to effectively load antitumor drugs, allowing for controlled and sustained release of the drugs locally and sustainably both in vitro and in vivo. In addition, the PGL ethanol gel can combine ethanol ablation and local chemotherapy to enhance the antitumor efficacy in vitro and in vivo. The PGL ethanol gel-derived hydrogel shows robust wet bioadhesion, drug loading, sustained release, good biocompatibility and biodegradability, easy preparation and usage, and cost-effectiveness, which make it a promising bioadhesive for diverse biomedical applications.

16.
J Orthop Translat ; 45: 10-23, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38434180

RESUMO

Background: Treatment of chronic osteomyelitis (bone infection) remains a clinical challenge; in particular, it requires enhanced delivery of antibiotic drugs for the treatment of intracellular Staphylococcus aureus (S. aureus), which prevents infection recurrence and resistance. Previous studies have found that noninvasive shock waves used to treat musculoskeletal diseases can alter cell permeability, however, it is unclear whether shock waves alter cell membrane permeability in chronic osteomyelitis. Furthermore, it remains unknown whether such changes in permeability promote the entry of antibiotics into osteoblasts to exert antibacterial effects. Methods: In our study, trypan blue staining was used to determine the shock wave parameters that had no obvious damage to the osteoblast model; the effect of shocks waves on the cell membrane permeability of osteoblast model was detected by BODIPY®FL vancomycin; high performance liquid chromatography-mass spectrometry (HLPC-MS) was used to detect the effect of shock wave on the entry of antibiotics into the osteoblast model; plate colony counting method was used to detect the clearance effect of shock wave assisted antibiotics on S. aureus in the osteoblast model. To explore the mechanism, the effect of different pulses of shock waves on S. aureus was examined by plate colony counting method, besides, P2X7 receptor in osteoblast was detected by immunofluorescence and the extracellular ATP levels was detected. Furthermore, the effect of P2X7 receptor antagonists KN-62 or A740003 on the intracellular antibacterial activity of shock-assisted antibiotics was observed. Then, we used S. aureus to establish a rat model of chronic tibial osteomyelitis and investigated the efficacy and safety of shock-wave assisted antibiotics in the treatment of chronic osteomyelitis in rats. Results: The viability of the osteoblast models of intracellular S. aureus infection was not significantly affected by the application of up to 400 shock wave pulses at 0.21 mJ/mm2. Surprisingly, the delivery of BODIPY®FL vancomycin to osteoblast model cells was markedly enhanced by this shock wave treatment. Furthermore, the shock wave therapy increased the delivery of hydrophilic antibiotics (vancomycin and cefuroxime sodium), but not lipophilic antibiotics (rifampicin and levofloxacin), which improved the intracellular antibacterial effect. Afterwards, we discovered that shock wave treatment increased the extracellular concentration of ATP (the P2X7 receptor activator), while KN-62 or A740003, a P2X7 receptor inhibitor, decreased intracellular antibacterial activity. We then found that 0.1 mL of 1 × 1011 CFU/mL ATCC25923 S. aureus was suitable for modeling chronic osteomyelitis in rats. Besides, the shock wave-assisted vancomycin treatment with the strongest antibacterial and osteogenic effects among the tested treatments was confirmed in vivo by imaging examination, microbiological cultures, and histopathology, with favorable safety. Conclusions: Our results suggest that shock waves can promote the entry of antibiotics into osteoblasts for antibacteria by changing the cell membrane permeability in a P2X7 receptor-dependent manner. Besides, considering antibacterial and osteogenic efficiency and a high degree of safety in rat osteomyelitis model, shock wave-assisted vancomycin treatment may thus represent a possible adjuvant therapy for chronic osteomyelitis.

17.
Medicine (Baltimore) ; 103(10): e37413, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457553

RESUMO

BACKGROUND: Myocardial infarction (MI) is a cardiovascular disease that seriously threatens human health. However, an immune-related competitive endogenous RNA (ceRNA) network has not been reported in MI. METHODS: The GSE66360, GSE19339, GSE97320, GSE61741, and GSE168281 datasets were acquired from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRNAs) from MI patients and healthy controls were screened and an immune-related ceRNA network was constructed. Furthermore, the key long noncoding RNAs(lncRNAs) highly related to the immune mechanism of MI were identified utilizing the random walk with restart algorithm. Finally, the expression of the hub genes was further verified in the GSE66360, GSE19339, and GSE97320 datasets, and quantitativereal-time polymerase chain reaction (qRT-PCR) was performed for the MI patients and healthy controls. RESULTS: A total of 184 differentially expressed immune-related genes(DE-IRGs) and 432 DE-miRNAs were obtained, and an immune-related ceRNA network comprising 1421 lncRNAs, 61 DE-miRNAs, and 139 DE-IRGs was constructed. According to the order of stress, betweenness, and closeness, NEAT1, KCNQ1OT1, and XIST were identified as key lncRNAs. Moreover, random walk with restart analysis also suggested that NEAT1, KCNQ1OT1, and XIST are key lncRNAs. Subsequently, a ceRNA network of 10 hub genes and 3 lncRNAs was constructed. Finally, we found that the expression of FCER1G and TYROBP significantly differed between MI patients and control individuals in the GSE66360, GSE19339, and GSE97320 datasets. qRT-PCR revealed that the expression of NEAT1, KCNQ1OT1, XIST, FCER1G, and TYROBP was significantly elevated in MI tissue samples compared to healthy control tissue samples. CONCLUSION: NEAT1, KCNQ1OT1, XIST, FCER1G, and TYROBP are involved in MI and can be used as molecular biomarkers for the screening and diagnosis of MI. Furthermore, the immune system plays an essential role in the onset and progression of MI.


Assuntos
MicroRNAs , Infarto do Miocárdio , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , 60414 , MicroRNAs/genética , Infarto do Miocárdio/genética , Algoritmos , Redes Reguladoras de Genes
18.
Pestic Biochem Physiol ; 199: 105768, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38458677

RESUMO

Plant pathogenic bacteria can cause numerous diseases for higher plants and result in severe reduction of crop yield. Introduction of new bactericides can always effectively control these plant diseases. Benziothiazolinone (BIT) is a novel fungicide registered in China for the control of plant fungal diseases, however, its anti-bacterial activity is not well studied. The results of activity tests showed that BIT exhibited stronger inhibitory activity against bacteria, particularly for Xanthomonas oryzae pv. oryzae (Xoo) (EC50 = 0.17 µg/mL), which was superior than that of the tested fungi in vitro. BIT also exhibited excellent protective and curative activity against rice bacterial leaf blight (BLB) caused by Xoo with the control efficacies of 71.37% and 91.64% at 600 µg/mL, respectively. After treatment with BIT, Xoo cell surface became wrinkled and the cell shape was distorted with extruding cellular content. It was also found that BIT decreased DNA synthesis and affected the biofilm formation and motility of Xoo cells. However, no significant change in the protein content was observed. Moreover, the results of quantitative real-time PCR also showed that expressions of several genes related to DNA synthesis, biofilm formation and motility of Xoo cells were down- or up-regulated, which further proved the anti-bacterial activity of BIT in influencing the biological properties of Xoo. Additionally, BIT also enhanced the activity of phenylalanine ammonia lyase (PAL), a plant defense enzyme. Taken together, benziothiazolinone might be served as an alternative candidate for the control of BLB.


Assuntos
Oryza , Xanthomonas , Antibacterianos/farmacologia , DNA , China , Oryza/metabolismo , Doenças das Plantas/prevenção & controle , Doenças das Plantas/microbiologia
20.
Sensors (Basel) ; 24(6)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38544264

RESUMO

Imaging using scattering media is a very important yet challenging technology. As one of the most widely used scattering imaging methods, speckle autocorrelation technology has important applications in several fields. However, traditional speckle autocorrelation imaging methods usually use iterative phase recovery algorithms to obtain the Fourier phase of hidden objects, posing issues such as large data calculation volumes and uncertain reconstruction results. Here, we propose a single-shot scattering imaging method based on the bispectrum truncation method. The bispectrum analysis is utilized for hidden object phase recovery, the truncation method is used to avoid the computation of redundant data when calculating the bispectrum data, and the method is experimentally verified. The experimental results show that our method does not require uncertain iterative calculations and can reduce the bispectrum data computation by more than 80% by adjusting the truncation factor without damaging the imaging quality, which greatly improves imaging efficiency. This method paves the way for rapid imaging through scattering media and brings benefits for imaging in dynamic situations.

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