Epithelial Cells Research Articles

Hydrogel dressings on neurotrophic keratitis in an experimental animal model

AIM: To investigate the therapeutic effects of hydrogel dressings on neurotrophic keratitis in rats. METHODS: Male Wistar rats, aged 42–56d, were randomly divided into control, experimental, and treatment groups, each consisting of five rats. The experimental and treatment groups underwent neurotrophic keratitis modeling in both eyes. After successful modeling, biomedical hydrogels formed with polyvinyl alcohol and polyvinyl pyrrolidone were used in treatment group for 7d. Ocular irritation response and keratitis index scores, Schirmer’s test, tear film break-up time (BUT), sodium fluorescein staining, and hematoxylin and eosin (HE) staining were used to evaluate the effectiveness of the treatment. RESULTS: The neurotrophic keratitis model was successfully established in rats with severe ophthalmic nerve injury, characterized by keratitis, ocular irritation, reduced tear secretion measured by decreased BUT and Schirmer test values, corneal epithelial loss, and disorganized collagen fibers in the stromal layer. Following treatment with hydrogel dressings, significant improvements were observed in keratitis scores and ocular irritation symptoms in model eyes. Although the recovery of tear secretion, as measured by the Schirmer’s test, did not show statistical differences, BUT was significantly prolonged. Fluorescein staining confirmed a reduction in the extent of corneal epithelial loss after treatment. HE staining revealed the restoration of the structural disorder in both the epithelial and stromal layers to a certain extent. CONCLUSION: Hydrogel dressing reduces ocular surface irritation, improves tear film stability, and promotes the repair and restoration of damaged epithelial cells by maintaining a moist and clean environment on the ocular surface in the rat model.

Targeted inhibition of m6A demethylase FTO by FB23 attenuates allergic inflammation in the airway epithelium.

Epithelial cells play a crucial role in asthma, contributing to chronic inflammation and airway hyperresponsiveness. m6A modification, which involves key proteins such as the demethylase fat mass and obesity-associated protein (FTO), is crucial in the regulation of various diseases, including asthma. However, the role of FTO in epithelial cells and the development of asthma remains unclear. In this study, we investigated the demethylase activity of FTO using a small-molecule inhibitor FB23 in epithelial cells and allergic inflammation invivo and invitro. We examined the FTO-regulated transcriptome-wide m6A profiling by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq under FB23 treatment and allergic inflammation conditions. Immunofluorescence staining was performed to assess the tissue-specific expression of FTO in asthmatic bronchial mucosa. We demonstrated that FB23 alleviated allergic inflammation in IL-4/IL-13-treated epithelial cells and house dust mite (HDM)-induced allergic airway inflammation mouse model. The demethylase activity of FTO contributed to the regulation of TNF-α signaling via NF-κB and epithelial-mesenchymal transition-related pathways under allergic inflammation conditions in epithelial cells. FTO was expressed in epithelial, submucosal gland, and smooth muscle cells in human bronchial mucosa. In conclusion, FB23-induced inhibition of FTO alleviates allergic inflammation in epithelial cells and HDM-induced mice, potentially through diverse cellular processes and epithelial-mesenchymal transition signaling pathways, suggesting that FTO is a potential therapeutic target in asthma management.

Comprehensive single-cell analysis deciphered microenvironmental dynamics and immune regulator olfactomedin 4 in pathogenesis of gallbladder cancer

ObjectiveElucidating complex ecosystems and molecular features of gallbladder cancer (GBC) and benign gallbladder diseases is pivotal to proactive cancer prevention and optimal therapeutic intervention.DesignWe performed single-cell transcriptome analysis on 230...

In vitro anticancer, antioxidant, cytotoxic activity and phytochemical characterization of Inula viscosa L. essential oil against colorectal cancer cell line HCT-116

Human colorectal cancer cell line (HCT116) cells are adherent epithelial cells derived from the human colorectal carcinoma cell line commonly used to study inflammatory responses in colonic epithelial cells. This study aimed to evaluate the protective effects of Inula viscosa essential oil (IVEO), an effective antioxidant compound with a radical scavenging activity in vitro using HCT-116 cells. The chemical composition of hydrodistilled IVEO was analyzed by GC-FID and GC-MS systems. The major compounds of essential oil were borneol acetate (51.54%) and borneol (21.17%). The cytotoxicity was determined using the colorimetric MTT assay for 24 h, and 48 h. Malondialdehyde (MDA) level, some enzymes activities including catalase (CAT) and superoxide dismutase (SOD) were measured in the HCT 116 cells both with and without IVEO treatment. In this study, there was a significant decrease in activities of cellular SOD and CAT, increased in the MDA levels in the cells treated with IVEO. These result indicate that IVEO can serve as an agent with strong potential to be utilized for the development of colorectal cancer chemoprevention. However, further molecular investi-gation is required to understand the molecular bearings of IVEO.

T cell receptor clonotype in tumor microenvironment contributes to intratumoral signaling network in patients with colorectal cancer.

Single-cell RNA sequencing (scRNA-seq) has contributed to understanding cellular heterogeneity and immune profiling in cancer. The aim of the study was to investigate gene expression and immune profiling in colorectal cancer (CRC) using scRNA-seq. We analyzed single-cell gene expression and T cell receptor (TCR) sequences in 30 pairs of CRC and matched normal tissue. Intratumoral lymphocytes were measured with digital image analysis. CRC had more T cells, epithelial cells, and myeloid cells than normal colorectal tissue. CRCs with microsatellite instability had more abundant T cells than those without microsatellite instability. Immune cell compositions of CRC and normal colorectal tissue were inversely correlated. CD4 + or CD8 + proliferating T cells, CD4 + effector memory T cells, CD8 + naïve T cells, and regulatory T cells of CRC showed higher TCR clonal expansion. Tumor epithelial cells interacted with immune cells more strongly than normal. T cells, myeloid cells, and fibroblasts from CRCs of expanded T cell clonotypes showed increased expression of genes related to TNF and NFKB signaling and T cell activation. CRCs of expanded T cell clonotypes also showed stronger cellular interactions among immune cells, fibroblasts, and endothelial cells. Pro-inflammatory CXCL and TNF signaling were activated in CRCs of expanded T cell clonotype. In conclusion, scRNA-seq analysis revealed different immune cell compositions, differential gene expression, and diverse TCR clonotype dynamics in CRC. TCR clonality expansion is associated with immune activation through T cell signaling and chemokine signaling. Patients with CRCs of expanded clonotype can be promising candidates for immunotherapy.

Altered expression and localization of nuclear envelope proteins in a prostate cancer cell system.

The nuclear envelope (NE), which is composed of the outer and inner nuclear membranes, the nuclear pore complex and the nuclear lamina, regulates a plethora of cellular processes, including those that restrict cancer development (genomic stability, cell cycle regulation, and cell migration). Thus, impaired NE is functionally related to tumorigenesis, and monitoring of NE alterations is used to diagnose cancer. However, the chronology of NE changes occurring during cancer evolution and the connection between them remained to be precisely defined, due to the lack of appropriate cell models. The expression and subcellular localization of NE proteins (lamins A/C and B1 and the inner nuclear membrane proteins emerin and β-dystroglycan [β-DG]) during prostate cancer progression were analyzed, using confocal microscopy and western blot assays, and a prostate cancer cell system comprising RWPE-1 epithelial prostate cells and several prostate cancer cell lines with different invasiveness. Deformed nuclei and the mislocalization and low expression of lamin A/C, lamin B1, and emerin became more prominent as the invasiveness of the prostate cancer lines increased. Suppression of lamin A/C expression was an early event during prostate cancer evolution, while a more extensive deregulation of NE proteins, including β-DG, occurred in metastatic prostate cells. The RWPE-1 cell line-based system was found to be suitable for the correlation of NE impairment with prostate cancer invasiveness and determination of the chronology of NE alterations during prostate carcinogenesis. Further study of this cell system would help to identify biomarkers for prostate cancer prognosis and diagnosis.

GSK3 inhibition reduces ECM production and prevents age-related macular degeneration-like pathology.

Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD) is an age-related macular degeneration-like (AMD-like) retinal dystrophy caused by an autosomal dominant R345W mutation in the secreted glycoprotein, fibulin-3 (F3). To identify new small molecules that reduce F3 production in retinal pigmented epithelium (RPE) cells, we knocked-in a luminescent peptide tag (HiBiT) into the endogenous F3 locus that enabled simple, sensitive, and high-throughput detection of the protein. The GSK3 inhibitor, CHIR99021 (CHIR), significantly reduced F3 burden (expression, secretion, and intracellular levels) in immortalized RPE and non-RPE cells. Low-level, long-term CHIR treatment promoted remodeling of the RPE extracellular matrix, reducing sub-RPE deposit-associated proteins (e.g., amelotin, complement component 3, collagen IV, and fibronectin), while increasing RPE differentiation factors (e.g., tyrosinase, and pigment epithelium-derived factor). In vivo, treatment of 8-month-old R345W+/+ knockin mice with CHIR (25 mg/kg i.p., 1 mo) was well tolerated and significantly reduced R345W F3-associated AMD-like basal laminar deposit number and size, thereby preventing the main pathological feature in these mice. This is an important demonstration of small molecule-based prevention of AMD-like pathology in ML/DHRD mice and may herald a rejuvenation of interest in GSK3 inhibition for the treatment of retinal degenerative diseases, including potentially AMD itself.

Mesoporous zinc-polyphenol nanozyme for attenuating renal ischemia-reperfusion injury.

Aim: To target the reactive oxygen species (ROS) accumulation and renal tubular epithelial cell (rTEC) death in renal ischemia-reperfusion injury (IRI), we constructed a nanoparticle that offers ROS scavenging and rTEC-death inhibition: mesoporous zinc-tannic acid nanozyme (ZnTA). Materials & methods: After successfully constructing ZnTA, we proceeded to examine its effect on ROS accumulation, cellular ferroptosisand apoptosis, as well as injury severity. Results: Malondialdehyde, Fe2+ amounts and 4-HNE staining demonstrated that ZnTA effectively attenuated rTEC ferroptosis. TUNEL staining confirmed that Zn2+ carried by ZnTA could effectively inhibit caspase 3 and caspase 9, mitigating apoptosis. Finally, it reduced renal IRI through the synergistic effect of ROSscavenging and cell-death inhibition. Conclusion: This study is expected to provide a paradigm for a combined therapeutic strategy for renal IRI.

The effects of infectious dosages on endogenous phage and the excretion of Eimeria tenella oocysts of infected chicken

This study was conducted to evaluate the effects of four dosages of oocyst inoculation (1×102, 1×103, 1×104, and 1×105 oocysts/chick) on oocyst patterns in feces, lesion score, and the endogenous phase of Eimeria tenella in the tissue of infected chickens. Oocysts in feces were collected daily from 4 to 10 day-post-infection (dpi). Chickens were killed at 0, 3, 5, and 10 dpi to evaluate the lesion score and the endogenous phage in the tissue by hematoxylin and eosin staining. The results showed that chickens in the highest dosage group discharged oocysts the earliest (5 dpi), while oocysts were detected in the other 3 groups 1 day later (6 dpi). The results of the histopathological examination showed that the time to detect the development stages of E. tenella in the tissue was similar among the experimental groups. Specifically, the asexual stages (1st and 2nd schizonts) were detected at 3 dpi, and immature oocysts were found in the cecum tissue at 5 dpi in all experimental groups. Overall, the results indicated that the oocyst dosages do not affect the replication of E. tenella in intestinal epithelial cells but may influence the excretion of oocysts from the intestinal tissue.

TRB3 Promotes Cataract Progression through Endoplasmic Reticulum Stress-mediated Mitochondrial Dysfunction and Cell Apoptosis.

Cataracts are characterized as a disease affecting lens opacity. Endoplasmic reticulum (ER) stress can cause lens epithelial cell (LEC) dysfunction, affecting normal lens transparency and function, but the role of Tribbles 3 (TRB3), an inducible gene of ER stress, in cataracts is poorly understood. This study explored how TRB3 promotes cataract progression through ER stress. We administered a subcutaneous injection of sodium selenite at a dosage of 3.46 mg/kg to rats to create an animal model of cataracts. Additionally, we exposed rat LEC cells to 0.01 μM tunicamycin (TM) for 24 h to establish a cell model of ER stress. The detection of related genes and proteins was performed via RT‒qPCR and Western blot techniques. Flow cytometry, along with JC-1, TUNEL, and HE staining, was employed to assess damage to cells and lens tissues. This study revealed that TRB3 was abnormally highly expressed in both a cataract rat model and an ER stress cell model. Knocking down TRB3 has a similar effect as treatment with an ER stress inhibitor, effectively reversing the ER stress and apoptosis induced by TM. This effect includes increasing the mitochondrial membrane potential in LEC cells, lowering reactive oxygen species (ROS) levels, increasing ATP production, suppressing the expression of the apoptosis-related proteins Bax and C-caspase-3, increasing Bcl-2 expression, and decreasing apoptosis. Furthermore, TRB3 knockdown improved the pathological conditions of rat lenses and inhibited mitochondrial dysfunction and cell apoptosis to relieve the development of cataracts in rats. Mechanistically, CHOP promotes the expression of TRB3 by binding to the TRB3 promoter, thereby activating ER stress, leading to mitochondrial dysfunction and cell apoptosis in LEC cells and accelerating the development of cataracts. According to our findings, targeting TRB3 expression inhibition could emerge as a novel approach for cataract therapy.

Melatonin alleviates palmitic acid-induced mitochondrial dysfunction by reducing oxidative stress and enhancing autophagy in bovine endometrial epithelial cells

BackgroundNegative energy balance (NEB) typically occurs in dairy cows after delivery. Cows with a high yield are more likely to experience significant NEB. This type of metabolic imbalance could cause ketosis, which is often accompanied by a decline in reproductive performance. However, the molecular mechanisms underlying NEB have yet to be fully elucidated. During excessive NEB, the body fat is extensively broken down, resulting in the abnormal accumulation of non-esterified fatty acids (NEFAs), represented by palmitic acid (PA), within the uterus. Such an abnormal accumulation has the potential to damage bovine endometrial epithelial cells (BEECs), while the molecular mechanisms underlying its involvement in the PA-induced injury of BEECs remains poorly understood. Melatonin (MT) is recognized for its regulatory role in maintaining the homeostasis of mitochondrial reactive oxygen species (mitoROS). However, little is known as to whether MT could ameliorate the damage incurred by BEECs in response to PA and the molecular mechanism involved.ResultsAnalysis showed that 0.2 mmol/L PA stress increased the level of cellular and mitochondrial oxidative stress, as indicated by increased reactive oxygen species (ROS) level. In addition, we observed mitochondrial dysfunction, including abnormal mitochondrial structure and respiratory function, along with a reduction in mitochondrial membrane potential and mitochondrial copy number, and the induction of apoptosis. Notably, we also observed the upregulation of autophagy proteins (PINK, Parkin, LC3B and Ubiquitin), however, the P62 protein was also increased. As we expected, 100 μmol/L of MT pre-treatment attenuated PA-induced mitochondrial ROS and restored mitochondrial respiratory function. Meanwhile, MT pretreatment reversed the upregulation of P62 induced by PA and activated the AMPK-mTOR-Beclin-1 pathway, contributing to an increase of autophagy and decline apoptosis.ConclusionsOur findings indicate that PA can induce mitochondrial dysfunction and enhance autophagy in BEECs. In addition, MT is proved to not only reduce mitochondrial oxidative stress but also facilitate the clearance of damaged mitochondria by upregulating autophagy pathways, thereby safeguarding the mitochondrial pool and promoting cellular viability. Our study provides a better understanding of the molecular mechanisms underlying the effect of an excess of NEB on the fertility outcomes of high yielding dairy cows.

The activation of cGAS-STING pathway causes abnormal uterine receptivity in aged mice.

Maternal age is one of the most important factors affecting the success of maternal pregnancy. Uterine aging is the leading cause of pregnancy failure in older women. However, how uterine aging affects uterine receptivity and decidualization is unclear. In this study, naturally aged one-year-old female mice were used to investigate effects of maternal age on embryo implantation during early pregnancy. In our study, we found abnormal uterine receptivity in aged mice. Aged mouse uterus indicates a decrease in nuclear LAMIN A, and an increase in PRELAMIN A and PROGERIN. In aged mouse uterus, double-stranded DNA (dsDNA) in cytoplasmic fraction is significantly increased. PROGERIN overexpression in mouse uterine epithelial cells and epithelial organoids leads to nuclear DNA leakage and impaired uterine receptivity. DNase I, DNase II, and TREX1 are obviously reduced in aged mouse uterus. Treatments with foreign DNA or STING agonist significantly downregulate uterine receptivity markers and activate cGAS-STING pathway. Uterine estrogen (E2) concentration is significantly increased in aged mice. After ovariectomized mice are treated with a high level of E2, there are significant increase of PROGERIN and cytoplasmic DNA, and activation of cGAS-STING pathway. CD14 is significantly increased in aged uterus. Intrauterine CD14 injection inhibits embryo implantation. Invitro CD14 treatment of cultured epithelial cells or epithelial organoids decreases uterine receptivity. Uterine abnormality in aged mouse can be partially rescued by STING inhibitor. In conclusion, uterine PROGERIN increase in aged mouse uterus results in cytoplasmic DNA accumulation and cGAS-STING pathway activation. CD14 secretion in aged uterus impairs uterine receptivity.

The Microenvironment of Solid Tumors: Components and Current Challenges of Tumor-on-a-Chip Models.

Solid tumors represent the most common type of cancer in humans and are classified into sarcomas, lymphomas, and carcinomas based on the originating cells. Among these, carcinomas, which arise from epithelial and glandular cells lining the body's tissues, are the most prevalent. Around the world, a significant increase in the incidence of solid tumors is observed during recent years. In this context, efforts to discover more effective cancer treatments have led to a deeper understanding of the tumor microenvironment (TME) and its components. Currently, the interactions between cancer cells and elements of the TME are being intensely investigated. Remarkable progress in research is noted, largely owing to the development of advanced in vitro models, such as tumor-on-a-chip models that assist in understanding and ultimately discovering new effective treatments for a specific type of cancer. The purpose of this article is to provide a review of the TME and cancer cell components, along with the advances on tumor-on-a-chip models designed to mimic tumors, offering a perspective on the current state of the art. Recent studies using this kind of microdevices that reproduce the TME have allowed a better understanding of the cancer and its treatments. Nevertheless, current applications of this technology present some limitations that must be overcome to achieve a broad application by researchers looking for a deeper knowledge of cancer and new strategies to improve current therapies.

2D TiO2 Nanosheets Decorated Via Sphere-Like BiVO4: A Promising Non-Toxic Material for Liquid Phase Photocatalysis and Bacterial Eradication.

An in-depth investigation was conducted on a promising composite material (BiVO4/TiO2), focusing on its potential toxicity, photoinduced catalytic properties, as well as its antibiofilm and antimicrobial functionalities. The preparation process involved the synthesis of 2D TiO2 using the lyophilization method, which was subsequently functionalized with sphere-like BiVO4 through wet impregnation. Finally, we developed BiVO4/TiO2 S-scheme heterojunctions which can greatly promote the separation of electron-hole pairs to achieve high photocatalytic performance. The evaluation of concentration- and time-dependent viability inhibition was performed on human lung carcinoma epithelial A549 cells. This assessment included the estimation of glutathione levels and mitochondrial dehydrogenase activity. Significantly, the BiVO4/TiO2 composite demonstrated minimal toxicity towards A549 cells. Impressively, the BiVO4/TiO2 composite exhibited notable photocatalytic performance in the degradation of rhodamine B (k=0.135 min-1) and phenol (k=0.016 min-1). In terms of photoinduced antimicrobial performance, the composite effectively inactivated both gram-negative E. coli and gram-positive E. faecalis bacteria upon 60 minutes of UV-A light exposure, resulting in a significant log 6 (log 10 CFU/mL) reduction in bacterial count. In addition, a 49 % reduction of E. faecalis biofilm was observed. These promising results can be attributed to the unique 2D morphology of TiO2 modified by sphere-like BiVO4, leading to an increased generation of (intracellular) hydroxyl radicals, which plays a crucial role in the treatments of both organic pollutants and bacteria. This research has significant potential for various applications, particularly in addressing environmental contamination and microbial infections.

A spatial expression atlas of the adult human proximal small intestine.

The mouse small intestine shows profound variability in gene expression along the crypt-villus axis1,2. Whether similar spatial heterogeneity exists in the adult human gut remains unclear. Here we use spatial transcriptomics, spatial proteomics and single-molecule fluorescence in situ hybridization to reconstruct a comprehensive spatial expression atlas of the adult human proximal small intestine. We describe zonated expression and cell type representation for epithelial, mesenchymal and immune cell types. We find that migrating enterocytes switch from lipid droplet assembly and iron uptake at the villus bottom to chylomicron biosynthesis and iron release at the tip. Villus tip cells are pro-immunogenic, recruiting γδ T cells and macrophages to the tip, in contrast to their immunosuppressive roles in mouse. We also show that the human small intestine contains abundant serrated and branched villi that are enriched at the tops of circular folds. Our study presents a detailed resource for understanding the biology of the adult human small intestine.

Age-related epithelial defects limit thymic function and regeneration.

The thymus is essential for establishing adaptive immunity yet undergoes age-related involution that leads to compromised immune responsiveness. The thymus is also extremely sensitive to acute insult and although capable of regeneration, this capacity declines with age for unknown reasons. We applied single-cell and spatial transcriptomics, lineage-tracing and advanced imaging to define age-related changes in nonhematopoietic stromal cells and discovered the emergence of two atypical thymic epithelial cell (TEC) states. These age-associated TECs (aaTECs) formed high-density peri-medullary epithelial clusters that were devoid of thymocytes; an accretion of nonproductive thymic tissue that worsened with age, exhibited features of epithelial-to-mesenchymal transition and was associated with downregulation of FOXN1. Interaction analysis revealed that the emergence of aaTECs drew tonic signals from other functional TEC populations at baseline acting as a sink for TEC growth factors. Following acute injury, aaTECs expanded substantially, further perturbing trophic regeneration pathways and correlating with defective repair of the involuted thymus. These findings therefore define a unique feature of thymic involution linked to immune aging and could have implications for developing immune-boosting therapies in older individuals.

Effects of the S1P/S1PR1 Signaling Pathway on High Glucose-Induced NRK-52E Epithelial-Mesenchymal Transition Via Regulation of ROS/NLRP3.

Diabetic kidney disease (DKD) is the most significant complication in diabetic patients, ultimately leading to renal fibrosis. The most important manifestation of DKD is the epithelial-mesenchymal transition (EMT) of renal tubular cells, which can lead to renal fibrosis and inflammatory injury in special situations. Sphingosine 1-phosphate (S1P) is involved in various signal transduction pathways and plays a role through G protein-coupled receptors. Research has demonstrated that blocking the S1P / S1PR2pathway inhibits inflammation and fibrosis. However, the interaction between S1P/S1PR1and the pathophysiology of EMT remains ambiguous. The purpose of this study was to investigate the mechanism of S1P/S1PR1 on high glucose (HG)-induced renal EMT. We found that HG markedly increased the S1P and EMT marker levels in renal tubular epithelial cells. At the same time, HG could stimulate NF-κB/ROS/NLRP3 expression, but these phenomena were reversed after blocking S1PR1. In mice models of DKD, FTY720 (S1P antagonist) could significantly improve renal function and reduce the infiltration of inflammatory cells. ROS, as well as NLPR3 inflammasome, were markedly decreased in the treatment group. FTY720 inhibits extracellular matrix synthesis and improves renal fibrosis. In brief, the HG stimulates S1P/S1PR1 synthesis and activates the S1P/S1PR1 pathway. Through the S1P/S1PR1 pathway, activates NF-κB, promotes ROS generation and NLRP3 inflammasome activation, and ultimately causes EMT.

Total Synthesis and Anti-inflammatory Activity of Asperjinone and Asperimide C.

Total syntheses of two γ-butenolide natural products, asperjinone (1) and asperimide C (2) in both racemic and chiral forms have been accomplished utilizing Basavaiah's one-pot Friedel-Crafts/maleic anhydride formation protocol as a key strategy. Our syntheses verified the revised structure of 1 proposed by Williams et al. and the structure and absolute configuration of 2 reported by the Li group. This work also discloses the unprecedented anti-inflammatory activity of 1. Synthetic 1 exhibited significant anti-inflammatory activity in renal proximal tubular epithelial cells (RPTEC) by suppression of gene expression of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 under LPS-induced renal inflammation condition and was superior to (S)-1, rac-2, 2, and a positive drug control, indomethacin. Moreover, compound 1 inhibited downstream signaling of inflammation by significantly reducing iNOS and COX-2 gene expression and total NO production. The anti-inflammatory activity of asperjinone (1) renders it a potential and promising candidate for developing novel anti-inflammatory agents against inflammation worsening acute kidney injury.

TNKS1BP1 mediates AECII senescence and radiation induced lung injury through suppressing EEF2 degradation

BackgroundAlthough recent studies provide mechanistic understanding to the pathogenesis of radiation induced lung injury (RILI), rare therapeutics show definitive promise for treating this disease. Type II alveolar epithelial cells (AECII) injury in various manner results in an inflammation response to initiate RILI.ResultsHere, we reported that radiation (IR) up-regulated the TNKS1BP1, causing progressive accumulation of the cellular senescence by up-regulating EEF2 in AECII and lung tissue of RILI mice. Senescent AECII induced Senescence-Associated Secretory Phenotype (SASP), consequently activating fibroblasts and macrophages to promote RILI development. In response to IR, elevated TNKS1BP1 interacted with and decreased CNOT4 to suppress EEF2 degradation. Ectopic expression of EEF2 accelerated AECII senescence. Using a model system of TNKS1BP1 knockout (KO) mice, we demonstrated that TNKS1BP1 KO prevents IR-induced lung tissue senescence and RILI.ConclusionsNotably, this study suggested that a regulatory mechanism of the TNKS1BP1/CNOT4/EEF2 axis in AECII senescence may be a potential strategy for RILI.

Association between COVID-19 Severity and Expression of Viral Nucleic Acid Sensor Genes in Peripheral Blood Mononuclear Cells and Nasopharyngeal Epithelial Cells.

This study examined expression of key viral nucleic acid sensor genes MDA5, ZBP1, and AIM2 in nasopharyngeal epithelial cells and peripheral blood mononuclear cells (PBMCs) obtained from 153 COVID-19 patients across a spectrum of disease severity (mild, severe, and critical) and 42 healthy controls. Quantitative reverse transcription polymerase chain reaction was used to quantify and compare sensor transcript levels. The COVID-19 cohort had a mean age of 53.6 years. All three sensor genes including MDA5 (3.2-fold), ZBP1 (5.1-fold), and AIM2 (4.7-fold) exhibited significantly higher messenger RNA expression in both nasopharyngeal and PBMC samples from infected patients compared with healthy controls. Furthermore, sensor transcript upregulation positively correlated with escalating disease severity. During early stages, ZBP1 and AIM2 transcripts were selectively elevated within the nasopharyngeal compartment, suggesting a localized antiviral response. Whereas later during critical disease stages, ZBP1 and AIM2 levels became preferentially heightened within circulating PBMCs, indicating systemic immune cell activation. By comparison, MDA5 elevation manifested within nasopharyngeal epithelial cells during both early- and late-phase infection. Intriguingly, males displayed higher ZBP1 and AIM2 expression compared with females, whereas MDA5 transcript levels were conversely higher among females. Overall, escalation of these key viral sensor genes appears closely linked to COVID-19 progression, with initial nasal mucosal upregulation transitioning to widespread blood cell activation in severe systemic disease. These patterns of sensor expression suggest frontline immunological efforts to constrain early viral invasion and combat severe late-stage COVID-19 illness through innate detection of replicating SARS-CoV-2.