Association between psoriasis and asthma: a systematic review and bidirectional meta-analysis.

BACKGROUND: The risk of asthma in patients with psoriasis has been identified in previous studies, but the bidirectional association between the two has not been fully explored. METHODS: We thoroughly searched PubMed, Embase, and the Cochrane Library to find relevant observational studies published from the inception of these databases to October 2023. All the risk and bias assessments were analyzed by STATA 16.0. Where the heterogeneity was less than 50%, the fixed effect model was utilized. While where the level of heterogeneity was more than 50%, the random effect model was applied. Moreover, to identify publication bias, a visual funnel chart, and Egger's test were applied. RESULTS: A total of 12,396,911 participants from 16 studies, published between 2011 and 2023 were included in this meta-analysis. We found that psoriasis patients had a higher risk of developing asthma (OR = 1.48, 95%CI 1.28-1.68). Meanwhile, asthma patients also had a higher overall risk of developing psoriasis (OR = 1.33, 95%CI 1.23-1.44). In the subgroup analysis, we found that the type of study, age, and severity of the psoriasis were significant factors in the survey of asthma risk in psoriasis patients. CONCLUSIONS: In the present systematic review and meta-analysis, we found a bidirectional association between psoriasis and asthma with significantly increased risk. As a result, clinicians should make patients aware of the connection between the two, particularly adolescents or patients with moderate to severe psoriasis who need to be informed about the rising likelihood of developing asthma. TRIAL REGISTRATION: Registration number CRD42023390111 .

Dual modality intravascular catheter system combining pulse-sampling fluorescence lifetime imaging and polarization-sensitive optical coherence tomography.

The clinical management of coronary artery disease and the prevention of acute coronary syndromes require knowledge of the underlying atherosclerotic plaque pathobiology. Hybrid imaging modalities capable of comprehensive assessment of biochemical and morphological plaques features can address this need. Here we report the first implementation of an intravascular catheter system combining fluorescence lifetime imaging (FLIm) with polarization-sensitive optical coherence tomography (PSOCT). This system provides multi-scale assessment of plaque structure and composition via high spatial resolution morphology from OCT, polarimetry-derived tissue microstructure, and biochemical composition from FLIm, without requiring any molecular contrast agent. This result was achieved with a low profile (2.7 Fr) double-clad fiber (DCF) catheter and high speed (100 fps B-scan rate, 40 mm/s pullback speed) console. Use of a DCF and broadband rotary junction required extensive optimization to mitigate the reduction in OCT performance originating from additional reflections and multipath artifacts. This challenge was addressed by the development of a broad-band (UV-visible-IR), high return loss (47 dB) rotary junction. We demonstrate in phantoms, ex vivo swine coronary specimens and in vivo swine heart (percutaneous coronary access) that the FLIm-PSOCT catheter system can simultaneously acquire co-registered FLIm data over four distinct spectral bands (380/20 nm, 400/20 nm, 452/45 nm, 540/45 nm) and PSOCT backscattered intensity, birefringence, and depolarization. The unique ability to collect complementary information from tissue (e.g., morphology, extracellular matrix composition, inflammation) with a device suitable for percutaneous coronary intervention offers new opportunities for cardiovascular research and clinical diagnosis.

Pulse-sampling fluorescence lifetime imaging: evaluation of photon economy.

This Letter presents an experimental study comparing the photon rate and photon economy of pulse sampling fluorescence lifetime imaging (PS-FLIm) with the conventional time-correlated single photon counting (TCSPC) technique. We found that PS-FLIm has a significantly higher photon detection rate (200 MHz) compared with TCSPC (2-8 MHz) but lower photon economy (4-5 versus 1-1.3). The main factor contributing to the lower photon economy in PS-FLIm is laser pulse variability. These results demonstrate that PS-FLIm offers 25× faster imaging speed than TCSPC while maintaining room light rejection in clinical settings. This makes PS-FLIm a robust technique for clinical applications.

Restricted Phase Space Thermodynamics of Einstein-Power-Yang-Mills AdS Black Hole.

We consider the thermodynamics of the Einstein-power-Yang-Mills AdS black holes in the context of the gauge-gravity duality. Under this framework, Newton's gravitational constant and the cosmological constant are varied in the system. We rewrite the thermodynamic first law in a more extended form containing both the pressure and the central charge of the dual conformal field theory, i.e., the restricted phase transition formula. A novel phenomena arises: the dual quantity of pressure is the effective volume, not the geometric one. That leads to a new behavior of the Van de Waals-like phase transition for this system with the fixed central charge: the supercritical phase transition. From the Ehrenfest's scheme perspective, we check out the second-order phase transition of the EPYM AdS black hole. Furthermore the effect of the non-linear Yang-Mills parameter on these thermodynamic properties is also investigated.

Multimodal fluorescence lifetime imaging and optical coherence tomography for longitudinal monitoring of tissue-engineered cartilage maturation in a preclinical implantation model.

Significance: Cartilage tissue engineering is a promising strategy for effective curative therapies for treatment of osteoarthritis. However, tissue engineers depend predominantly on time-consuming, expensive, and destructive techniques as quality control to monitor the maturation of engineered cartilage. This practice can be impractical for large-scale biomanufacturing and prevents spatial and temporal monitoring of tissue growth, which is critical for the fabrication of clinically relevant-sized cartilage constructs. Nondestructive multimodal imaging techniques combining fluorescence lifetime imaging (FLIm) and optical coherence tomography (OCT) hold great potential to address this challenge. Aim: The feasibility of using multimodal FLIm-OCT for nondestructive, spatial, and temporal monitoring of self-assembled cartilage tissue maturation in a preclinical mouse model is investigated. Approach: Self-assembled cartilage constructs were developed for 4 weeks in vitro followed by 4 weeks of in vivo maturation in nude mice. Sterile and nondestructive in situ multispectral FLIm and OCT imaging were carried out at multiple time points ( t = 2 , 4, and 8 weeks) during tissue development. FLIm and 3D volumetric OCT images were reconstructed and used for the analysis of tissue biochemical homogeneity, morphology, and structural integrity. A biochemical homogeneity index was computed to characterize nonhomogeneous tissue growth at different time points. OCT images were validated against histology. Results: FLIm detects heterogenous extracellular matrix (ECM) growth of tissue-engineered cartilage. The outer edge of the tissue construct exhibited longer fluorescence lifetime in 375 to 410 and 450 to 485 nm spectral channels, indicating increase in collagen content. Significant ( p < 0.05 ) decrease of construct homogeneity index was observed between t = 2 weeks and t = 4 weeks. Both FLIm and OCT images revealed defects (voids) at the center of the tissue construct during in vitro culture ( t = 2 and 4 weeks). Cyst formation during in vivo culture was detected by OCT and confirmed with histology. Conclusions: The ability of multimodal FLIm-OCT to nondestructively monitor the heterogenous growth of engineered tissue constructs in situ is demonstrated. Spatial and temporal variation of construct ECM component was detected by FLIm. OCT reveals structural defects (voids and cysts). This multimodal approach has great potential to replace costly destructive tests in the manufacturing of tissue-engineered medical products, facilitating their clinical translation.

Intraoperative detection of IDH-mutant glioma using fluorescence lifetime imaging.

Identifying isocitrate dehydrogenase (IDH)-mutation and glioma subtype during surgery instead of days later can aid in modifying tumor resection strategies for better survival outcomes. We report intraoperative identification of IDH-mutant glioma (N = 12 patients) with a clinically compatible fluorescence lifetime imaging (FLIm) device (excitation: 355 nm; emission spectral bands: 390/40 nm, 470/28 nm, 542/50 nm). The fluorescence-derived parameters were analyzed to study the optical contrast between IDH-mutant tumors and surrounding brain tissue. IDH-mutant oligodendrogliomas exhibited shorter lifetimes (3.3 ± 0.1 ns) than IDH-mutant astrocytomas (4.1 ± 0.1 ns). Both IDH-mutant glioma subtypes had shorter lifetimes than white matter (4.6 ± 0.4 ns) but had comparable lifetimes to cortex. Lifetimes also increased with malignancy grade within IDH-mutant oligodendrogliomas (grade 2: 2.96 ± 0.08 ns, grade 3: 3.4 ± 0.3 ns) but not within IDH-mutant astrocytomas. The current results support the feasibility of FLIm as a surgical adjuvant for identifying IDH-mutant glioma tissue.

Non-destructive, continuous monitoring of biochemical, mechanical, and structural maturation in engineered tissue.

Regulatory guidelines for tissue engineered products require stringent characterization during production and necessitate the development of novel, non-destructive methods to quantify key functional parameters for clinical translation. Traditional assessments of engineered tissues are destructive, expensive, and time consuming. Here, we introduce a non-destructive, inexpensive, and rapid sampling and analysis system that can continuously monitor the mechanical, biochemical, and structural properties of a single sample over extended periods of time. The label-free system combines the imaging modalities of fluorescent lifetime imaging and ultrasound backscatter microscopy through a fiber-based interface for sterile monitoring of tissue quality. We tested the multimodal system using tissue engineered articular cartilage as an experimental model. We identified strong correlations between optical and destructive testing. Combining FLIm and UBM results, we created a novel statistical model of tissue homogeneity that can be applied to tissue engineered constructs prior to implantation. Continuous monitoring of engineered tissues with this non-destructive system has the potential for in-process monitoring of tissue engineered products, reducing costs and improving quality controls in research, manufacturing, and clinical applications.

Dual-modality fluorescence lifetime imaging-optical coherence tomography intravascular catheter system with freeform catheter optics.

SIGNIFICANCE: Intravascular imaging is key to investigations into atherosclerotic plaque pathobiology and cardiovascular diagnostics overall. The development of multimodal imaging devices compatible with intracoronary applications has the potential to address limitations of currently available single-modality systems. AIM: We designed and characterized a robust, high performance multimodal imaging system that combines optical coherence tomography (OCT) and multispectral fluorescence lifetime imaging (FLIm) for intraluminal simultaneous assessment of structural and biochemical properties of coronary arteries. APPROACH: Several shortcomings of existing FLIm-OCT catheter systems are addressed by adopting key features, namely (1) a custom fiber optic rotary joint based on an air bearing, (2) a broadband catheter using a freeform reflective optics, and (3) integrated solid-state FLIm detectors. Improvements are quantified using a combination of experimental characterization and simulations. RESULTS: Excellent UV and IR coupling efficiencies and stability (IR: 75.7 % ± 0.4 % , UV: 45.7 % ± 0.35 % ) are achieved; high FLIm optical performance is obtained (UV beam FWHM: 50 µm) contemporaneously with excellent OCT beam quality (IR beam FWHM: 17 µm). High-quality FLIm OCT image of a human coronary artery specimen was acquired. CONCLUSION: The ability of this intravascular imaging system to provide comprehensive structural and biochemical properties will be valuable to further our understanding of plaque pathophysiology and improve cardiovascular diagnostics.

Prognostic significance of pyroptosis-related factors in lung adenocarcinoma.

Background: Numerous studies have revealed that the abnormal expression of pyroptosis-related genes is closely related to the prognosis of lung adenocarcinoma (LUAD); however, a comprehensive analysis has yet to be conducted. This study aimed to reveal the influence of pyroptosis-related genes on the prognosis of LUAD and establish a prognostic model based on those genes, in order to evaluate the prognosis of LUAD. Methods: The data of tumor and normal samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differential analysis was used to identify pyroptosis-related genes (obtained from the GeneCards database) that were differentially expressed (DE) in TCGA database. Univariate and stepwise multivariate Cox proportional hazards regression analyses were used to screen feature genes related to LUAD overall survival (OS) and construct gene signature. Gene set enrichment analysis (GSEA) was then performed to reveal potential functions related to gene signature. Finally, the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was used to reveal distinctions in each cell-subtype groups in the immune landscape of LUAD. Results: Overall, 26 DE genes (DEGs) associated with pyroptosis were obtained. Among them, 4 (MKI67, BTK, MST1, and TUBB6) were selected as prognostic genes and a 4-gene signature with a good prognostic performance in the TCGA and GEO was constructed. The gene signature was shown to be an independent prognostic factor of LUAD in subsequent analysis. Functional enrichment indicated that the 4-gene signature may participate in the tumorigenesis and development of LUAD through various pathways related to tumor progression to play a prognostic role in LUAD. Additionally, the results of the immune landscape indicated that the 4-gene signature may affect the prognosis of LUAD via cooperating with changes in the immune microenvironment. Conclusions: The key biomarkers and pathways identified in this study would deepen the comprehension of the molecular mechanism of pyroptosis in LUAD. More importantly, the 4-gene signature may serve as a novel potential prognostic model for LUAD.

First in patient assessment of brain tumor infiltrative margins using simultaneous time-resolved measurements of 5-ALA-induced PpIX fluorescence and tissue autofluorescence.

SIGNIFICANCE: 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is currently used for image-guided glioma resection. Typically, this widefield imaging method highlights the bulk of high-grade gliomas, but it underperforms at the infiltrating edge where PpIX fluorescence is not visible to the eyes. Fluorescence lifetime imaging (FLIm) has the potential to detect PpIX fluorescence below the visible detection threshold. Moreover, simultaneous acquisition of time-resolved nicotinamide adenine (phosphate) dinucleotide [NAD(P)H] fluorescence may provide metabolic information from the tumor environment to further improve overall tumor detection. AIM: We investigate the ability of pulse sampling, fiber-based FLIm to simultaneously image PpIX and NAD(P)H fluorescence of glioma infiltrative margins in patients. APPROACH: A mesoscopic fiber-based point-scanning FLIm device (355 nm pulses) was used to simultaneously resolve the fluorescence decay of PpIX (629/53 nm) and NAD(P)H (470/28 nm). The FLIm device enabled data acquisition at room light and rapid (<33 ms) augmentation of FLIm parameters on the surgical field-of-view. FLIm measurements from superficial tumors and tissue areas around the resection margins were performed on three glioblastoma patients in vivo following inspection of PpIX visible fluorescence with a conventional neurosurgical microscope. Microbiopsies were collected from FLIm imaged areas for histopathological evaluation. RESULTS: The average lifetime from PpIX and NAD(P)H fluorescence distinguished between tumor and surrounding tissue. FLIm measurements of resection margins presented a range of PpIX and NAD(P)H lifetime values (τPpIX   ∼ 3 to 14 ns, τNAD(P)H = 3 to 6 ns) associated with unaffected tissue and areas of low-density tumor infiltration. CONCLUSIONS: Intraoperative FLIm could simultaneously detect the emission of PpIX and NAD(P)H from patients in vivo during craniotomy procedures. This approach doubles as a clinical tool to identify tumor areas while performing tissue resection and as a research tool to study tumor microenvironmental changes in vivo. Intraoperative FLIm of 5-ALA-induced PpIX and tissue autofluorescence makes a promising surgical adjunct to guide tumor resection surgery.

Multispectral fluorescence lifetime imaging device with a silicon avalanche photodetector.

We report the design, development, and characterization of a novel multi-spectral fluorescence lifetime measurement device incorporating solid-state detectors and automated gain control. For every excitation pulse (∼1 µJ, 600 ps), this device records complete fluorescence decay from multiple spectral channels simultaneously within microseconds, using a dedicated UV enhanced avalanche photodetector and analog to digital convert (2.5 GS/s) in each channel. Fast (<2 ms) channel-wise dynamic range adjustment maximizes the signal-to-noise ratio. Fluorophores with known lifetime ranging from 0.5-6.0 ns were used to demonstrate the device accuracy. Current results show the clear benefits of this device compared to existing devices employing microchannel-plate photomultiplier tubes. This is demonstrated by 5-fold reduction of lifetime measurement variability in identical conditions, independent gain adjustment in each spectral band, and 4-times faster imaging speed. The use of solid-state detectors will also facilitate future improved performance and miniaturization of the instrument.

Traditional Chinese Medicine Xihuang Wan Inhibited Lewis Lung Carcinoma in a Syngeneic Model, Equivalent to Cytotoxic Chemotherapy, by Altering Multiple Signaling Pathways.

BACKGROUND/AIM: Xihuang Wan (XHW), a traditional Chinese medicine (TCM), has been used in China for a variety of cancers including lung cancer. The present study evaluated the efficacy of XHW on a Lewis lung mouse model and explored the potential mechanism via transcriptomics. MATERIALS AND METHODS: The mice were randomized into 6 groups: 1) untreated control (n=10); 2) low-dose XHW; 3) medium-dose XHW; 4) high-dose XHW; 5) cisplatin; and 6) untreated blank (n=4). Lewis lung carcinoma (LLC) cells were injected subcutaneously except for the 4 mice in the blank group. The body weight and tumor length and width were measured every 3 days. RNA-sequencing was performed on tumors in the high-dose XHW group and the control group. RESULTS: XHW inhibited the growth of LLC in a syngeneic mouse model, without toxicity, with equivalent efficacy to cisplatin. RNA-sequencing demonstrated that many signaling pathways were involved in XHW-mediated inhibition of LLC, including tumor necrosis factor, estrogen, cyclic guanosine 3', 5'-monophosphate-protein kinase G, apelin and the peroxisome proliferator-activated receptor signaling pathways. CONCLUSION: XHW inhibited LLC carcinoma through different pathways and shows clinical promise for patients who cannot tolerate platinum-based drugs.

Mesoscopic fluorescence lifetime imaging: Fundamental principles, clinical applications and future directions.

Fluorescence lifetime imaging (FLIm) is an optical spectroscopic imaging technique capable of real-time assessments of tissue properties in clinical settings. Label-free FLIm is sensitive to changes in tissue structure and biochemistry resulting from pathological conditions, thus providing optical contrast to identify and monitor the progression of disease. Technical and methodological advances over the last two decades have enabled the development of FLIm instrumentation for real-time, in situ, mesoscopic imaging compatible with standard clinical workflows. Herein, we review the fundamental working principles of mesoscopic FLIm, discuss the technical characteristics of current clinical FLIm instrumentation, highlight the most commonly used analytical methods to interpret fluorescence lifetime data and discuss the recent applications of FLIm in surgical oncology and cardiovascular diagnostics. Finally, we conclude with an outlook on the future directions of clinical FLIm.

FLIm-Guided Raman Imaging to Study Cross-Linking and Calcification of Bovine Pericardium.

Bovine pericardium (BP) is a vascular biomaterial used in cardiovascular surgery that is typically cross-linked for masking antigenicity and enhance stability. There is a need for biochemical evaluation of the tissue properties prior to implantation to ensure that quality and reliability standards are met. Here, engineered antigen removed BP (ARBP) that was cross-linked with 0.2% and 0.6% glutaraldehyde (GA), and further calcified in vitro to simulate graft calcifications upon implantation was characterized nondestructively using fluorescence lifetime imaging (FLIm) to identify regions of interest which were then assessed by Raman spectroscopy. We observed that the tissue fluorescence lifetime shortened, and that Raman bands at 856, 935, 1282, and 1682 cm-1 decreased, and at 1032 and 1627 cm-1 increased with increasing GA cross-linking. Independent classification analysis based on fluorescence lifetime and on Raman spectra discriminated between GA-ARBP and untreated ARBP with an accuracy of 91% and 66%, respectively. Pearson's correlation analysis showed a strong correlation between pyridinium cross-links measured with high-performance liquid chromatography and fluorescence lifetime measured at 380-400 nm (R = -0.76, p = 0.00094), as well as Raman bands at 856 cm-1 for hydroxy-proline (R = -0.68, p = 0.0056) and at 1032 cm-1 for hydroxy-pyridinium (R = 0.74, p = 0.0016). Calcified areas of GA cross-linked tissue showed characteristic hydroxyapatite (959 and 1038 cm-1) bands in the Raman spectrum and fluorescence lifetime shortened by 0.4 ns compared to uncalcified regions. FLIm-guided Raman imaging could rapidly identify degrees of cross-linking and detected calcified regions with high chemical specificity, an ability that can be used to monitor tissue engineering processes for applications in regenerative medicine.

Multiscale, multispectral fluorescence lifetime imaging using a double-clad fiber.

Fiber-based imaging of tissue autofluorescence using ultraviolet (UV) excitation is a highly flexible tool used to probe structure and composition. In this Letter, we report, to the best of our knowledge, the first results from a single-fiber imaging system employing a custom double-clad fiber to acquire multispectral fluorescence lifetime images at two distinct spatial resolutions. We characterize the lateral point spread function and fluorescent background of the system and show how enhanced resolution can identify features such as trabeculae in ex vivo murine bone samples.

Non-destructive detection of matrix stabilization correlates with enhanced mechanical properties of self-assembled articular cartilage.

Tissue engineers rely on expensive, time-consuming, and destructive techniques to monitor the composition, microstructure, and function of engineered tissue equivalents. A non-destructive solution to monitor tissue quality and maturation would greatly reduce costs and accelerate the development of tissue-engineered products. The objectives of this study were to (a) determine whether matrix stabilization with exogenous lysyl oxidase-like protein-2 (LOXL2) with recombinant hyaluronan and proteoglycan link protein-1 (LINK) would result in increased compressive and tensile properties in self-assembled articular cartilage constructs, (b) evaluate whether label-free, non-destructive fluorescence lifetime imaging (FLIm) could be used to infer changes in both biochemical composition and biomechanical properties, (c) form quantitative relationships between destructive and non-destructive measurements to determine whether the strength of these correlations is sufficient to replace destructive testing methods, and (d) determine whether support vector machine (SVM) learning can predict LOXL2-induced collagen crosslinking. The combination of exogenous LOXL2 and LINK proteins created a synergistic 4.9-fold increase in collagen crosslinking density and an 8.3-fold increase in tensile strength as compared with control (CTL). Compressive relaxation modulus was increased 5.9-fold with addition of LOXL2 and 3.4-fold with combined treatments over CTL. FLIm parameters had strong and significant correlations with tensile properties (R2  = 0.82; p < 0.001) and compressive properties (R2  = 0.59; p < 0.001). SVM learning based on FLIm-derived parameters was capable of automating tissue maturation assessment with a discriminant ability of 98.4%. These results showed marked improvements in mechanical properties with matrix stabilization and suggest that FLIm-based tools have great potential for the non-destructive assessment of tissue-engineered cartilage.

Detection of glycosaminoglycan loss in articular cartilage by fluorescence lifetime imaging.

Glycosaminoglycan (GAG) loss is an early marker of osteoarthritis, which is a clinical late stage disease that affects millions of people worldwide. The goal of our study was to evaluate the ability of a fiber-based fluorescence lifetime imaging (FLIm) technique to detect GAG loss in articular cartilage. Native bovine cartilage explants (n = 20) were exposed to 0 (control), 0.5 (low), or 1 U / mL (high) concentrations of chondroitinase ABC (cABC) to create samples with different levels of GAG loss. FLIm assessment (excitation: 355 nm; detection: channel 1: 375 to 410 nm, channel 2: 450 to 485 nm, channel 3: 530 to 565 nm) was conducted on depth-resolved cross-sections of the cartilage sample. FLIm images, validated with histology, revealed that loss of GAG resulted in a decrease of fluorescence lifetime values in channel 2 (Δ = 0.44 ns, p < 0.05) and channel 3 (Δ = 0.75 ns, p < 0.01) compared to control samples (channel 2: 6.34 ns; channel 3: 5.22 ns). Fluorescence intensity ratio values were lower in channel 1 (37%, p < 0.0001) and channel 2 (31% decrease, p < 0.0001) and higher in channel 3 (23%, p < 0.0001) relative to control samples. These results show that FLIm can detect the loss of GAG in articular cartilage and support further investigation into the feasibility of in vivo FLIm arthroscopy.

Histone Deacetylase 1 Inhibition Protects Against Hypoxia-Induced Swelling in H9c2 Cardiomyocytes Through Regulating Cell Stiffness.

BACKGROUND: The process of cardiomyocyte swelling involves changes of biomechanical properties and profiles of cellular genes. Although many genes have been proved to regulate cell edema of cardiomyocyte, the mechanisms involved in this event, as well as the biomechanical properties of swelling cell, remain unknown.Methods and Results:Whether histone deacetylase 1 (HDAC1) inhibition protects against hypoxia-induced H9c2 cardiomyocyte swelling is examined in this study. Hypoxia-induced changes in the biomechanical properties and cytoskeletal structure that are relevant to cell swelling were also determined. H9c2 cells were treated under a chemical hypoxia situation (cobalt chloride) with HDAC1 inhibition (chemical inhibitor or siRNA) for 5 h, followed by in vitro biological and mechanical characterization. The results showed that expression of HDAC1 instead of HDAC4 was upregulated by chemical hypoxia. HDAC1 inhibition protects H9c2 cells against chemical hypoxia-induced hypoxic injury and cell swelling. HDAC1 inhibition improved cell viability, decreased lactate dehydrogenase leakage, cell apoptosis, malondialdehyde concentration, cell volume, and particles on the cell surface, and increased superoxide dismutase activity. Moreover, chemical hypoxia induced a decrease of Young's modulus, accompanied by alterations in the integrity of acetylated histone and organization of the cytoskeletal network. HDAC1 inhibition significantly reversed these processes. CONCLUSIONS: Based on the ideal physical model, HDAC1 inhibition protects against hypoxia-induced swelling in H9c2 cardiomyocytes through enhancing cell stiffness. Overall, HDAC1 is a potential therapeutic target for myocardial edema.