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1.
Ann Clin Microbiol Antimicrob ; 23(1): 40, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702782

ABSTRACT

BACKGROUND: Pretomanid is a key component of new regimens for the treatment of drug-resistant tuberculosis (TB) which are being rolled out globally. However, there is limited information on the prevalence of pre-existing resistance to the drug. METHODS: To investigate pretomanid resistance rates in China and its underlying genetic basis, as well as to generate additional minimum inhibitory concentration (MIC) data for epidemiological cutoff (ECOFF)/breakpoint setting, we performed MIC determinations in the Mycobacterial Growth Indicator Tube™ (MGIT) system, followed by WGS analysis, on 475 Mycobacterium tuberculosis (MTB) isolated from Chinese TB patients between 2013 and 2020. RESULTS: We observed a pretomanid MIC distribution with a 99% ECOFF equal to 0.5 mg/L. Of the 15 isolates with MIC values > 0.5 mg/L, one (MIC = 1 mg/L) was identified as MTB lineage 1 (L1), a genotype previously reported to be intrinsically less susceptible to pretomanid, two were borderline resistant (MIC = 2-4 mg/L) and the remaining 12 isolates were highly resistant (MIC ≥ 16 mg/L) to the drug. Five resistant isolates did not harbor mutations in the known pretomanid resistant genes. CONCLUSIONS: Our results further support a breakpoint of 0.5 mg/L for a non-L1 MTB population, which is characteristic of China. Further, our data point to an unexpected high (14/475, 3%) pre-existing pretomanid resistance rate in the country, as well as to the existence of yet-to-be-discovered pretomanid resistance genes.


Subject(s)
Antitubercular Agents , Microbial Sensitivity Tests , Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , China/epidemiology , Humans , Antitubercular Agents/pharmacology , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Multidrug-Resistant/epidemiology , Prevalence , Nitroimidazoles/pharmacology , Genotype , Mutation , Whole Genome Sequencing
2.
One Health ; 18: 100735, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38711479

ABSTRACT

Background: Borrelia miyamotoi is a spirochete species transmitted via hard ticks. Following its discovery in Japan, this pathogen has been detected around the world, and is increasingly confirmed as a human pathogen causing febrile disease, namely relapsing fever. Its presence has been confirmed in the Northeast China. However, there is little information regarding the presence of B. miyamotoi and other hard-tick-borne relapsing fever spirochetes in southern China including Yunnan province, where tick and animal species are abundant and many people both inhabit and visit for recreation. Methods: For the present study, we collected samples of ticks, wildlife, and domestic animal hosts from different counties in Yunnan province. Nucleic acids from samples were extracted, and the presence of B. miyamotoi and other relapsing fever spirochetes was confirmed using polymerase chain reaction (PCR) for the 16S rRNA specific target gene fragment. The positive samples were then amplified for partial genome of the flaB and glpQ genes. Statistical differences in its distribution were analyzed by SPSS 20 software. Sequence of partial 16S rRNA, flaB and glpQ genome were analyzed and phylogenetic trees were constructed. Results: A total of 8260 samples including 2304 ticks, 4120 small mammals and 1836 blood of domestic animal hosts were collected for screening for infection of B. miyamotoi and other relapsing fever spirochetes. Cattle and sheep act as the main hosts and Rhipicephalus microplus, Haemaphysalis nepalensis, H. kolonini and Ixodes ovatus were identified as the important vector host with high prevalence or wide distribution. Only one Mus caroli (mouse) and one Sorex alpinus (shrew) were confirmed positive for relapsing fever spirochetes. Evidence of vertical transmission in ticks was also confirmed. Two known strains of B. miyamotoi and one novel relapsing fever spirochetes, B. theileri-like agent, were confirmed and described with their host adaptation, mutation, and potential risk of spreading and spillover for human beings. Conclusions: Our results provide new evidence of relapsing fever spirochetes in vector and animal hosts in Yunnan province based on large sample sizes, and offer guidance on further investigation, surveillance and monitoring of this pathogen.

3.
BMC Ophthalmol ; 24(1): 225, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38807037

ABSTRACT

BACKGROUND: We describe a case in which bilateral optic nerve infiltration and leukemic retinopathy were the initial signs of disease relapse in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+-ALL) with central nervous system (CNS) involvement. CASE PRESENTATION: A 65-year-old Asian female with Ph+-ALL in complete remission presented at our institution with symptoms of visual disturbance, central scotoma and pain with eye movement in both eyes for a 1-month duration. Ophthalmic examination revealed remarkable optic disc swelling with multiple flame-shaped peripapillary hemorrhages, retinal venous dilation and retinal hemorrhages in both eyes. She was subsequently referred to the treating oncologist and diagnosed with Ph+-ALL relapse with multiple relapsed diseases involving the bone marrow and CNS. After intrathecal (IT) therapy, her visual acuity dramatically improved, and her leukemic infiltrates decreased. CONCLUSIONS: To the best of our knowledge, this is the first case report of ALL relapse with CNS involvement presenting as bilateral optic nerve infiltration and leukemic retinopathy in an adult. Hence, we highlight the priority and sensitivity of ophthalmic examinations, as they are noninvasive methods for detecting leukemia relapse.


Subject(s)
Leukemic Infiltration , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Female , Aged , Leukemic Infiltration/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Optic Nerve/pathology , Optic Nerve/diagnostic imaging , Retinal Diseases/diagnosis , Retinal Diseases/etiology , Magnetic Resonance Imaging , Neoplasm Recurrence, Local , Visual Acuity/physiology
4.
Mol Neurobiol ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38767837

ABSTRACT

Cerebral ischemia-reperfusion injury produces excessive reactive oxygen and nitrogen species, including superoxide, nitric oxide, and peroxynitrite (ONOO-). We recently developed a new ONOO--triggered metal-free carbon monoxide donor (PCOD585), exhibiting a notable neuroprotective outcome on the rat middle cerebral artery occlusion model and rendering an exciting intervention opportunity toward ischemia-induced brain injuries. However, its therapeutic mechanism still needs to be addressed. In the pharmacological study, we found PCOD585 inhibited neuronal Bcl2/Bax/caspase-3 apoptosis pathway in the peri-infarcted area of stroke by scavenging ONOO-. ONOO- scavenging further led to decreased Acyl-CoA synthetase long-chain family member 4 and increased glutathione peroxidase 4, to minimize lipoperoxidation. Additionally, the carbon monoxide release upon the ONOO- reaction with PCOD585 further inhibited the neuronal Iron-dependent ferroptosis associated with ischemia-reperfusion. Such a synergistic neuroprotective mechanism of PCOD585 yields as potent a neuroprotective effect as Edaravone. Additionally, PCOD585 penetrates the blood-brain barrier and reduces the degradation of zonula occludens-1 by inhibiting matrix metalloproteinase-9, thereby protecting the integrity of the blood-brain barrier. Our study provides a new perspective for developing multi-functional compounds to treat ischemic stroke.

5.
J Orthop Surg Res ; 19(1): 308, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38773639

ABSTRACT

BACKGROUND: Intervertebral disc degeneration (IDD) is an increasingly important cause of low back pain (LBP) that results in substantial health and economic burdens. Inflammatory pathway activation and the production of reactive oxygen species (ROS) play vital roles in the progression of IDD. Several studies have suggested that phillyrin has a protective role and inhibits inflammation and the production of ROS. However, the role of phillyrin in IDD has not been confirmed. PURPOSE: The purpose of this study was to investigate the role of phillyrin in IDD and its mechanisms. STUDY DESIGN: To establish IDD models in vivo, ex-vivo, and in vitro to verify the function of phillyrin in IDD. METHOD: The effects of phillyrin on extracellular matrix (ECM) degeneration, inflammation, and oxidation in nucleus pulposus (NP) cells were assessed using immunoblotting and immunofluorescence analysis. Additionally, the impact of phillyrin administration on acupuncture-mediated intervertebral disc degeneration (IDD) in rats was evaluated using various techniques such as MRI, HE staining, S-O staining, and immunohistochemistry (IHC). RESULT: Pretreatment with phillyrin significantly inhibited the IL-1ß-mediated reduction in the degeneration of ECM and apoptosis by alleviating activation of the NF-κB inflammatory pathway and the generation of ROS. In addition, in vivo and ex-vivo experiments verified the protective effect of phillyrin against IDD. CONCLUSION: Phillyrin can attenuate the progression of IDD by reducing ROS production and activating inflammatory pathways.


Subject(s)
Disease Progression , Intervertebral Disc Degeneration , NF-kappa B , Rats, Sprague-Dawley , Reactive Oxygen Species , Intervertebral Disc Degeneration/metabolism , Intervertebral Disc Degeneration/pathology , Animals , Reactive Oxygen Species/metabolism , NF-kappa B/metabolism , Rats , Male , Nucleus Pulposus/metabolism , Nucleus Pulposus/drug effects , Nucleus Pulposus/pathology , Signal Transduction/drug effects , Extracellular Matrix/metabolism , Extracellular Matrix/drug effects , Disease Models, Animal , Cells, Cultured , Humans , Apoptosis/drug effects
6.
Heliyon ; 10(9): e29805, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38694087

ABSTRACT

Abnormalities in pulmonary vasculature or technical issues during lung procurement can lead to an insufficient left atrial (LA) cuff in donors. However, surgeons frequently need to reconfigure these less-than-ideal lungs for transplantation. This case report introduces a novel technique for such reconstruction. The patient was a 35-year-old male diagnosed with pneumoconiosis for over a year. Due to progressive worsening dyspnoea leading to respiratory failure on multiple occasions, he was deemed a candidate for lung transplantation. While obtaining the donor's lung, an inadvertent short cut of the LA cuff around the left inferior pulmonary vein orifice resulted in the residual vein retracting into the pulmonary hilum. To overcome this, we employed the aortic arch for reconstruction, enabling the successful completion of the lung transplantation. On post-transplantation day 2, extracorporeal membrane oxygenation was no longer required. Mechanical ventilation ceased after 13 days, with the subsequent removal of a tracheostomy. The patient spent 35 days in the intensive care unit and 58 days in the hospital. Post-transplantation complications included primary graft dysfunction, acute kidney failure, pneumothorax in the transplanted lung, the clots in the inferior vena cava, and pneumonia. Remarkably, over a year of follow-up (19 months after lung transplantation), the patient reported no adverse events and had successfully returned to work. In this case, the aortic arch is an alternative for reconstructing an insufficient LA cuff.

7.
J Org Chem ; 89(10): 7225-7232, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38712792

ABSTRACT

Bispidine, a bridged bicyclic diamine, has been widely utilized as a rigid scaffold in chiral chelating ligands in asymmetric synthesis. In particular, a chiral bispidine-quinolizidine hybrid, such as sparteine, was utilized in asymmetric synthesis involving a metal, exhibiting superior catalytic activity. In this study, we report the design and synthesis of a series of sparteine-derived organocatalysts and the utilization of these catalysts in tandem Michael addition-cyclization reactions. These catalysts have shown excellent catalytic reactivity and enantioselectivity, and the corresponding dihydropyrano[c]chromenes have been prepared in ≤99% yield and ≤99% ee with a low catalyst loading. The recycled catalysts maintain a good catalytic performance even after four cycles, and a gram-scale reaction with a 1% catalyst loading is also performed, providing the product in 96% yield and 98% ee.

8.
J Am Chem Soc ; 146(19): 13536-13545, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38693624

ABSTRACT

Herein, we establish a remote hydrosulfonamidation (HSA) of alkenes using palladium catalysis, where N-fluoro-N-(fluoro-sulfonyl)-carbamate with a sulfur(VI) fluoride moiety is demonstrated as a good amidation reagent. The anti-Markovnikov HSA reaction of terminal alkenes and the remote HSA of internal alkenes are achieved to efficiently yield primary N-alkyl-N-(fluorosulfonyl)-carbamates. In addition, this protocol enables the high-value utilization of alkane by combining the dehydrogenation process. The generated N-alkyl products exhibit a unique reactivity of sulfur(VI) fluorides, which can be directly transferred to N-alkyl sulfamides or amines via the sulfur(VI) fluoride exchange reaction, thereby streamlining their synthesis. Moreover, a (pyridyl) benzazole-type ligand proved to be vital for the excellent chemo- and regioselectivities.

9.
Taiwan J Obstet Gynecol ; 63(3): 369-374, 2024 May.
Article in English | MEDLINE | ID: mdl-38802200

ABSTRACT

OBJECTIVE: To explore a precise association between tumor location and lymph node (LN) biopsy algorithm in uterine confined endometrial cancer (EC). MATERIALS AND METHODS: Patients with EC treated in the Department of Obstetrics and Gynecology, South Branch of Fujian Provincial Hospital were included in this observational retrospective study. Based on the procedure of treatment, patients were separated to stage I (2015.07-2019.09) and stage II (2019.09-2021.9). In each stage, patients were separated to high and low-risk group by the predicted results. Patients in the high-risk group received systematic lymphadenectomy in stage I and sentinel lymph node (SLN) dissection in stage II. The efficiency of lymph node metastasis (LNM) detection rates was compared between stage I and stage II cases. Precise lymph node biopsy algorithm was also constructed based on the outcomes of stage II. RESULTS: Overall, 43 patients, 28 in stage I and 15 in stage II, were included in the study. No recurrence or death cases had been found within follow-up terms. Based on the difference in the detection efficiency of LNM (p > 0.05), there was no difference between two stages. Thus, systematic lymphadenectomy and SLN biopsy provided similar success rates. The location of tumor site was also important for deciding whether pelvic or para-aortic SLN should be sampled for LNM. CONCLUSIONS: Precise SLN biopsy for EC confined to the uterus showed comparable LNM detection rate as systematic lymphadenectomy. EC location may be used to determine whether pelvic or para-aortic SLN sampling should be conducted for treatment.


Subject(s)
Endometrial Neoplasms , Lymph Node Excision , Lymph Nodes , Lymphatic Metastasis , Neoplasm Staging , Sentinel Lymph Node Biopsy , Humans , Female , Endometrial Neoplasms/pathology , Endometrial Neoplasms/surgery , Retrospective Studies , Middle Aged , Lymph Node Excision/methods , Lymphatic Metastasis/pathology , Sentinel Lymph Node Biopsy/methods , Aged , Lymph Nodes/pathology , Adult , Algorithms
10.
Front Pharmacol ; 15: 1407989, 2024.
Article in English | MEDLINE | ID: mdl-38769996

ABSTRACT

Osteosarcoma (OS) is notorious for its high malignancy, and conventional chemotherapy drugs, while killing tumor cells, often inflict significant harm on the patient's body. The tumor microenvironment of OS is characterized by high levels of hydrogen peroxide (H2O2). Leveraging this feature, we have developed Mg-ZIF nanoparticles, which incorporate magnesium (Mg) to confer robust peroxidase (POD)-like enzymatic activity. These Mg-ZIF nanozymes can generate highly lethal superoxide anions within tumor cells in a responsive manner, thereby achieving effective tumor destruction. Both in vitro and in situ OS models have corroborated the anti-tumor efficacy of Mg-ZIF nanozymes, while also validating their biosafety. The design of Mg-ZIF nanozymes opens a new avenue for the treatment of OS, offering a promising therapeutic strategy.

11.
Nat Commun ; 15(1): 4270, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769299

ABSTRACT

Néel spin-orbit torque allows a charge current pulse to efficiently manipulate the Néel vector in antiferromagnets, which offers a unique opportunity for ultrahigh density information storage with high speed. However, the reciprocal process of Néel spin-orbit torque, the generation of ultrafast charge current in antiferromagnets has not been demonstrated. Here, we show the experimental observation of charge current generation in antiferromagnetic metallic Mn2Au thin films using ultrafast optical excitation. The ultrafast laser pulse excites antiferromagnetic magnons, resulting in instantaneous non-equilibrium spin polarization at the antiferromagnetic spin sublattices with broken spatial symmetry. Then the charge current is generated directly via spin-orbit fields at the two sublattices, which is termed as the reciprocal phenomenon of Néel spin-orbit torque, and the associated THz emission can be detected at room temperature. Besides the fundamental significance on the Onsager reciprocity, the observed magnonic charge current generation in antiferromagnet would advance the development of antiferromagnetic THz emitter.

12.
BMC Public Health ; 24(1): 1358, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769474

ABSTRACT

BACKGROUND: Understanding factors associated with antiretroviral treatment (ART) adherence is crucial for ART success among people living with HIV (PLHIV) in the "test and treat" era. Multiple psychosocial factors tend to coexist and have a syndemic effect on ART adherence. We aimed to explore factors associated with ART adherence and the syndemic effect of multiple psychosocial factors on ART adherence among PLHIV newly starting ART in Guangdong Province, China. METHODS: Newly diagnosed PLHIV from six cities in Guangdong Province were recruited between May 2018 and June 2019, and then followed up from May 2019 to August 2020. Baseline and follow-up data were collected from a questionnaire and the national HIV surveillance system, the follow-up data of which were analyzed in this study. A Center for Adherence Support Evaluation (CASE) index > 10 points was defined as optimal ART adherence, which was measured via participants' self-reported adherence during follow-up survey. Multivariable logistic regression was used to identify factors associated with ART adherence. Exploratory factor analysis (EFA) and multi-order latent variable structural equation modeling (SEM) were performed to explore the syndemic effect of multiple psychosocial factors on ART adherence. RESULTS: A total of 734 (68.53%) follow-up participants were finally included in this study among the 1071 baseline participants, of whom 91.28% (670/734) had self-reported optimal ART adherence. Unemployment (aOR = 1.75, 95%CI: 1.01-3.02), no medication reminder (aOR = 2.28, 95%CI: 1.09-4.74), low medication self-efficacy (aOR = 2.28, 95%CI: 1.27-4.10), low social cohesion (aOR = 1.82, 95%CI: 1.03-3.19), no social participation (aOR = 5.65, 95%CI: 1.71-18.63), and ART side effects (aOR = 0.46, 95%CI: 0.26-0.81) were barriers to optimal ART adherence. The EFA and second-order latent variable SEM showed a linear relationship (standardized coefficient = 0.43, P < 0.001) between ART adherence and the latent psychosocial (syndemic) factor, which consisted of the three latent factors of medication beliefs and self-efficacy (standardized coefficient = 0.65, P < 0.001), supportive environment (standardized coefficient = 0.50, P < 0.001), and negative emotions (standardized coefficient=-0.38, P < 0.01). The latent factors of medication beliefs and self-efficacy, supportive environment, and negative emotions explained 42.3%, 25.3%, and 14.1% of the variance in the latent psychosocial factor, respectively. CONCLUSIONS: About nine out of ten PLHIV on ART in Guangdong Province self-reported optimal ART adherence. However, more efforts should be made to address barriers to optimal ART adherence.


Subject(s)
HIV Infections , Medication Adherence , Humans , HIV Infections/drug therapy , HIV Infections/psychology , China/epidemiology , Male , Female , Adult , Cross-Sectional Studies , Medication Adherence/statistics & numerical data , Medication Adherence/psychology , Middle Aged , Anti-Retroviral Agents/therapeutic use , Surveys and Questionnaires , Anti-HIV Agents/therapeutic use , Young Adult
13.
Nanotechnology ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38768574

ABSTRACT

The development of 6G networks has promoted related research based on terahertz communication. As submillimeter radiation, signal transportation via terahertz waves has several superior properties, including non-ionizing and easy penetration of non-metallic materials. This paper provides an overview of different terahertz detectors based on various mechanisms. Additionally, the detailed fabrication process, structural design, and the improvement strategies are summarized. Following that, it is essential and necessary to prevent the practical signal from noise, and methods such as wavelet transform, UM-MIMO and decoding have been introduced. This paper highlights the detection process of the terahertz wave system and signal processing after the collection of signal data. .

15.
Eur J Med Res ; 29(1): 257, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38689322

ABSTRACT

BACKGROUND: This study aimed to explore the expression, molecular mechanism and its biological function of potassium two pore domain channel subfamily K member 1 (KCNK1) in bladder cancer (BC). METHODS: We integrated large numbers of external samples (n = 1486) to assess KCNK1 mRNA expression levels and collected in-house samples (n = 245) for immunohistochemistry (IHC) experiments to validate at the KCNK1 protein level. Single-cell RNA sequencing (scRNA-seq) analysis was performed to further assess KCNK1 expression and cellular communication. The transcriptional regulatory mechanisms of KCNK1 expression were explored by ChIP-seq, ATAC-seq and ChIA-PET data. Highly expressed co-expressed genes (HECEGs) of KCNK1 were used to explore potential signalling pathways. Furthermore, the immunoassay, clinical significance and molecular docking of KCNK1 were calculated. RESULTS: KCNK1 mRNA was significantly overexpressed in BC (SMD = 0.58, 95% CI [0.05; 1.11]), validated at the protein level (p < 0.0001). Upregulated KCNK1 mRNA exhibited highly distinguishing ability between BC and control samples (AUC = 0.82 [0.78-0.85]). Further, scRNA-seq analysis revealed that KCNK1 expression was predominantly clustered in BC epithelial cells and tended to increase with cellular differentiation. BC epithelial cells were involved in cellular communication mainly through the MK signalling pathway. Secondly, the KCNK1 transcription start site (TSS) showed promoter-enhancer interactions in three-dimensional space, while being transcriptionally regulated by GRHL2 and FOXA1. Most of the KCNK1 HECEGs were enriched in cell cycle-related signalling pathways. KCNK1 was mainly involved in cellular metabolism-related pathways and regulated cell membrane potassium channel activity. KCNK1 expression was associated with the level of infiltration of various immune cells. Immunotherapy and chemotherapy (docetaxel, paclitaxel and vinblastine) were more effective in BC patients in the high KCNK1 expression group. KCNK1 expression correlated with age, pathology grade and pathologic_M in BC patients. CONCLUSIONS: KCNK1 was significantly overexpressed in BC. A complex and sophisticated three-dimensional spatial transcriptional regulatory network existed in the KCNK1 TSS and promoted the upregulated of KCNK1 expression. The high expression of KCNK1 might be involved in the cell cycle, cellular metabolism, and tumour microenvironment through the regulation of potassium channels, and ultimately contributed to the deterioration of BC.


Subject(s)
Gene Expression Regulation, Neoplastic , Potassium Channels, Tandem Pore Domain , Urinary Bladder Neoplasms , Humans , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Molecular Docking Simulation , Potassium Channels, Tandem Pore Domain/genetics , Potassium Channels, Tandem Pore Domain/metabolism , Signal Transduction , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology
16.
ACS Chem Neurosci ; 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38634698

ABSTRACT

Neuronal death resulting from ischemic stroke is the primary cause of adult mortality and disability, and effective neuroprotective agents for poststroke intervention are still lacking. Remote ischemic postconditioning (RIPostC) has demonstrated significant protective effects against ischemia in various organs; however, the specific mechanisms are not fully understood. This study investigated the potential neuroprotective mechanisms of RIPostC in the context of ischemic stroke. Using a rat model of middle cerebral artery occlusion, we found that RIPostC mitigated neurological damage, improved movement in the open-field test, and protected against neuronal apoptosis. In terms of energy metabolism, RIPostC enhanced ATP levels, suppressed lactate content, and increased the production of ketone bodies (KBs). In the ferroptosis assay, RIPostC protected against lipoperoxidation, reversed the reduction of glutathione peroxidase 4 (GPX4), and mitigated the excessive expression of long-chain acyl-CoA synthetase family member 4 (ACSL4). In oxygen-glucose deprivation/reoxygenation-treated HT22 cells, KBs maintained GPX4 levels, suppressed ACSL4 expression, and preserved the mitochondrial cristae number. However, the effect of KBs on the expression of GPX4, ACSL4, and the number of mitochondrial cristae was blocked by erastin. Moreover, both RIPostC and KBs reduced total iron and ferrous ion content by repressing iron transporters both in vitro and in vivo. In conclusion, KBs-induced mitigation of ferroptosis could represent a new therapeutic mechanism for RIPostC in treating stroke.

17.
Adv Healthc Mater ; : e2400717, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649143

ABSTRACT

Chronic local inflammation and excessive cell apoptosis in nucleus pulposus (NP) tissue are the main causes of intervertebral disc degeneration (IDD). Stimuli-responsive hydrogels have great potential in the treatment of IDD by facilitating localized and controlled drug delivery. Herein, an injectable drug-loaded dual stimuli-responsive adhesive hydrogel for microenvironmental regulation of IDD, is developed. The gelatin methacryloyl is functionalized with phenylboronic acid groups to enhance drug loading capacity and enable dual stimuli-responsive behavior, while the incorporation of oxidized hyaluronic acid further improves the adhesive properties. The prepared hydrogel exhibits an enhanced drug loading capacity for diol-containing drugs, pH- and reactive oxygen species (ROS)-responsive behaviors, excellent radical scavenging efficiency, potent antibacterial activity, and favorable biocompatibility. Furthermore, the hydrogel shows a beneficial protective efficacy on NP cells within an in vitro oxidative stress microenvironment. The in vivo results demonstrate the hydrogel's excellent therapeutic effect on treating IDD by maintaining water retention, restoring disc height, and promoting NP regeneration, indicating that this hydrogel holds great potential as a promising therapeutic approach for regulating the microenvironment and alleviating the progression of IDD.

18.
Sci Rep ; 14(1): 9520, 2024 04 25.
Article in English | MEDLINE | ID: mdl-38664452

ABSTRACT

The link between neonatal jaundice and urinary tract infection (UTI) remains debated, with congenital kidney and urinary tract anomalies (CAKUT) potentially playing a role. This population-based study aimed to analyze the correlations between neonatal jaundice, CAKUT, and concomitant UTI. The study cohort consisted of 2,078,122 live births from 2004 to 2014. We linked several population-based datasets in Taiwan to identify infants with unexplained neonatal jaundice and their mothers. The primary outcome was the rate of CAKUT occurring within 3 years after delivery, and the presence of concomitant UTI during neonatal jaundice hospitalization. Infants with neonatal jaundice had a significantly higher risk of CAKUT (adjusted odds ratio [aOR] 1.24, 95% confidence interval [CI] 1.11-1.39) during early childhood. Among the subtypes of CAKUT, obstructive uropathy, vesicoureteral reflux and other CAKUT were associated with an increased risk of neonatal jaundice. Infants who underwent intensive phototherapy, had a late diagnosis (> 14 days of postnatal age) or underwent a prolonged duration of phototherapy (> 3 days) exhibited a higher risk of concomitant UTI compared to other infants with jaundice. Our findings indicate a notable association between neonatal jaundice and increased risks of UTIs in the context of CAKUT. This study underscore the importance of vigilant monitoring and timely interventions for neonates presenting with jaundice, while acknowledging the complexity and variability in the progression of CAKUT and its potential connection to UTIs.


Subject(s)
Jaundice, Neonatal , Urinary Tract Infections , Vesico-Ureteral Reflux , Humans , Urinary Tract Infections/complications , Urinary Tract Infections/epidemiology , Jaundice, Neonatal/epidemiology , Jaundice, Neonatal/complications , Jaundice, Neonatal/etiology , Female , Infant, Newborn , Male , Taiwan/epidemiology , Risk Factors , Kidney/abnormalities , Infant , Urinary Tract/abnormalities , Urogenital Abnormalities/complications , Urogenital Abnormalities/epidemiology
19.
Oncol Rep ; 51(6)2024 06.
Article in English | MEDLINE | ID: mdl-38666534

ABSTRACT

Even under aerobic conditions, tumor cells can reprogram their metabolism to preferentially metabolize glucose into lactic acid. This abnormal metabolic pattern, known as the 'Warburg' effect or aerobic glycolysis, promotes cancer progression. Long non­coding RNAs (lncRNAs) are RNAs that are >200 nucleotides in length and do not have protein­coding capabilities. However, these RNAs play a key role in tumor development. There is increasing evidence to indicate that lncRNAs regulate glucose metabolism in tumor cells by affecting metabolic enzymes and some signaling pathways, thereby regulating the occurrence and progression of hepatocellular carcinoma (HCC). Therefore, it is crucial to understand which lncRNAs play a regulatory role in HCC glycolysis and to determine the related molecular mechanisms. The present review summarized and discussed the functions of lncRNAs, focusing on the regulatory mechanisms of lncRNAs in the process of glycolysis in HCC. In addition, the present review suggests the importance of lncRNAs as future therapeutic targets for antitumor cell metabolism.


Subject(s)
Carcinoma, Hepatocellular , Gene Expression Regulation, Neoplastic , Liver Neoplasms , RNA, Long Noncoding , Warburg Effect, Oncologic , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Glycolysis/genetics , Signal Transduction
20.
Nanoscale ; 16(20): 9770-9780, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38597919

ABSTRACT

Prussian blue nanoparticles exhibit the potential to be employed in bioanalytical applications due to their robust stability, peroxidase-like catalytic functionality, straightforward synthesis, and biocompatibility. An efficient approach is presented for the synthesis of nucleic acid-modified Prussian blue nanoparticles (DNA-PBNPs), utilizing nanoparticle porosity to adsorb nucleic acids (polyT). This strategic adsorption leads to the exposure of nucleic acid sequences on the particle surface while retaining catalytic activity. DNA-PBNPs further couple with functional nucleic acid sequences and aptamers through complementary base pairing to act as transducers in biosensors and amplify signal acquisition. Subsequently, we integrated a copper ion-dependent DNAzyme (Cu2+-DNAzyme) and a vascular endothelial growth factor aptamer (VEGF aptamer) onto screen-printed electrodes to serve as recognition elements for analytes. Significantly, our approach leverages DNA-PBNPs as a superior alternative to traditional enzyme-linked antibodies in electrochemical biosensors, thereby enhancing both the efficiency and adaptability of these devices. Our study conclusively demonstrates the application of DNA-PBNPs in two different biosensing paradigms: the sensitive detection of copper ions and vascular endothelial growth factor (VEGF). These results indicate the promising potential of DNA-modified Prussian blue nanoparticles in advancing bioanalytical sensing technologies.


Subject(s)
Biosensing Techniques , Copper , DNA, Catalytic , DNA , Electrochemical Techniques , Ferrocyanides , Vascular Endothelial Growth Factor A , Ferrocyanides/chemistry , Biosensing Techniques/methods , DNA, Catalytic/chemistry , Vascular Endothelial Growth Factor A/analysis , Copper/chemistry , DNA/chemistry , Aptamers, Nucleotide/chemistry , Nanoparticles/chemistry , Humans , Electrodes
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