Hepatocyte GPCR signaling regulates IRF3 to control hepatic stellate cell transdifferentiation.

BACKGROUND: Interferon Regulatory Factor 3 (IRF3) is a transcription factor that plays a crucial role in the innate immune response by recognizing and responding to foreign antigens. Recently, its roles in sterile conditions are being studied, as in metabolic and fibrotic diseases. However, the search on the upstream regulator for efficient pharmacological targeting is yet to be fully explored. Here, we show that G protein-coupled receptors (GPCRs) can regulate IRF3 phosphorylation through of GPCR-Gα protein interaction. RESULTS: IRF3 and target genes were strongly associated with fibrosis markers in liver fibrosis patients and models. Conditioned media from MIHA hepatocytes overexpressing IRF3 induced fibrogenic activation of LX-2 hepatic stellate cells (HSCs). In an overexpression library screening using active mutant Gα subunits and Phos-tag immunoblotting, Gαs was found out to strongly phosphorylate IRF3. Stimulation of Gαs by glucagon or epinephrine or by Gαs-specific designed GPCR phosphorylated IRF3. Protein kinase A (PKA) signaling was primarily responsible for IRF3 phosphorylation and Interleukin 33 (IL-33) expression downstream of Gαs. PKA phosphorylated IRF3 on a previously unrecognized residue and did not require reported upstream kinases such as TANK-binding kinase 1 (TBK1). Activation of Gαs signaling by glucagon induced IL-33 production in hepatocytes. Conditioned media from the hepatocytes activated HSCs, as indicated by α-SMA and COL1A1 expression, and this was reversed by pre-treatment of the media with IL-33 neutralizing antibody. CONCLUSIONS: Gαs-coupled GPCR signaling increases IRF3 phosphorylation through cAMP-mediated activation of PKA. This leads to an increase of IL-33 expression, which further contributes to HSC activation. Our findings that hepatocyte GPCR signaling regulates IRF3 to control hepatic stellate cell transdifferentiation provides an insight for understanding the complex intercellular communication during liver fibrosis progression and suggests therapeutic opportunities for the disease. Video Abstract.

Associations of long-term fluctuation in blood pressure and ocular perfusion pressure with visual field progression in normal-tension glaucoma.

BACKGROUD: The aim of this study was to investigate the associations between fluctuation in blood pressure (BP), ocular perfusion pressure (OPP) and visual field (VF) progression in normal-tension glaucoma (NTG). METHODS: This prospective, longitudinal study included 44 patients with NTG. Only newly diagnosed NTG patients who had not been treated with a glaucoma medication were included. Patients were examined every year for 7 years. Intraocular pressure (IOP), heart rate (HR), systolic BP (SBP), diastolic BP (DBP), ocular perfusion pressure (OPP), and diastolic ocular perfusion pressure (DOPP) were measured at the same time. Ophthalmic examinations, including perimetry, were performed also. Initial VF were compared with follow-up data after 7 years. RESULTS: After 7 years of follow-up, 9 of the 44 patients showed VF progression. The standard deviation (SD) of SBP and OPP were significantly associated with VF progression (P = 0.007, < 0.001, respectively). Multiple regression analysis showed that VF progression was significantly associated with SD of OPP (odds ratio, OR = 2.012, 95% CI = 1.016-3.985; P = 0.045). CONCLUSIONS: Fluctuation in OPP was associated with VF progression in patients with NTG.

High-Resolution Tactile-Sensation Diagnostic Imaging System for Thyroid Cancer.

In this study, we propose the direct diagnosis of thyroid cancer using a small probe. The probe can easily check the abnormalities of existing thyroid tissue without relying on experts, which reduces the cost of examining thyroid tissue and enables the initial self-examination of thyroid cancer with high accuracy. A multi-layer silicon-structured probe module is used to photograph light scattered by elastic changes in thyroid tissue under pressure to obtain a tactile image of the thyroid gland. In the thyroid tissue under pressure, light scatters to the outside depending on the presence of malignant and positive properties. A simple and easy-to-use tactile-sensation imaging system is developed by documenting the characteristics of the organization of tissues by using non-invasive technology for analyzing tactile images and judging the properties of abnormal tissues.

Tall cell carcinoma with reversed polarity of breast: Sonographic and magnetic resonance imaging findings.

Tall cell carcinoma with reversed polarity (TCCRP) of breast is a rare subtype of breast cancer, which show tall and columnar cells with nuclei of reversed polarity, resembles tall cell variant in papillary thyroid cancer. Only 78 cases in 20 published studies had been reported by 2021. TCCRP was recently included as a separate subgroup of rare tumors in the World Health Organization Blue Book Classification of breast tumors (5th edition). We describe a TCCRP case in a 64-year-old woman with detailed radiologic features including quantitative ultrasonography.

Treatment of patients with coronavirus disease 2019 and cross-infection in dental clinics in Korea.

OBJECTIVES: The aim of the study was to investigate patients with coronavirus disease 2019 (COVID-19) who visited dental clinics for treatment and to analyse the occurrence of additional COVID-19-confirmed cases according to the type of dental treatment and use of personal protective equipment (PPE). METHODS: Interviews were conducted in November 2021 via telephone, and written questionnaires were administered to dental hygienists working at the 24 dental clinics selected for the study, visited by patients with COVID-19. The survey focused on the visit date, the treatment received, whether or not the dental personnel wore PPE while treating the patient, and how the dental clinic and the public health centre with jurisdiction over the clinic responded after the patient's visit. RESULTS: Additional confirmed cases occurred in two of the 24 dental clinics included. In both cases, scaling was performed, dental personnel did not use a face shield, and patients with COVID-19 were asymptomatic. In 14 of the 22 dental clinics where additional confirmed cases did not occur, the dental personnel did not use face shields, and in 10 clinics, the dental personnel wore dental masks but not a KF94 mask. Based on these findings, which were obtained before the advent of the omicron variant, COVID-19 cross-infection did not appear to be high in dental clinics. CONCLUSION: The rate of COVID-19 cross-infection before the advent of the omicron variant appeared to be low in dental clinics in Korea. Therefore, patients have no reason to delay necessary dental treatment if dental personnel put effort into wearing PPE.

Role of Microbiota-Derived Metabolites in Alcoholic and Non-Alcoholic Fatty Liver Diseases.

Chronic liver disease encompasses diseases that have various causes, such as alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). Gut microbiota dysregulation plays a key role in the pathogenesis of ALD and NAFLD through the gut-liver axis. The gut microbiota consists of various microorganisms that play a role in maintaining the homeostasis of the host and release a wide number of metabolites, including short-chain fatty acids (SCFAs), peptides, and hormones, continually shaping the host's immunity and metabolism. The integrity of the intestinal mucosal and vascular barriers is crucial to protect liver cells from exposure to harmful metabolites and pathogen-associated molecular pattern molecules. Dysbiosis and increased intestinal permeability may allow the liver to be exposed to abundant harmful metabolites that promote liver inflammation and fibrosis. In this review, we introduce the metabolites and components derived from the gut microbiota and discuss their pathologic effect in the liver alongside recent advances in molecular-based therapeutics and novel mechanistic findings associated with the gut-liver axis in ALD and NAFLD.

Outcomes of acute lymphoblastic leukaemia in adolescent and young adult Korean patients.

This study used Korean national data to investigate the relationship between treatment patterns and outcomes in Korean adolescent and young-adult (AYA) acute lymphoblastic leukaemia (ALL) patients. Chemotherapy incorporating L-asparaginase was considered paediatric-inspired (PI), as opposed to adult protocols. In total, 65·3% of patients received PI therapy. Five-year overall survival (OS) of PI-treated patients outperformed adult protocols (63·1% vs. 40·4%; P < 0·0001); this trend was maintained within various age subgroups. Younger age, L-asparaginase therapy, and radiotherapy corresponded with superior OS by multivariable analysis. OS tends to improve with PI protocols that include L-asparaginase in AYA ALL, suggesting that therapy protocol is critical in the treatment performance of this group.

The Role of the Gut Microbiome in Liver Cirrhosis Treatment.

Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, diseases such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis and Wilson's disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease of other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver fibrosis.

The Inhibitory Effect of Nodakenin on Mast-Cell-Mediated Allergic Inflammation Via Downregulation of NF-κB and Caspase-1 Activation.

Nodakenin, a coumarin isolated from the roots of Angelicae gigas, is effective for treating function control disorders, bacterial infections, pain, diarrhea, vitamin E deficiency, and for relaxation of the uterus. The aim of this study was to investigate the antiallergic related inflammatory effects in phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1) or anaphylactic activity in a mouse model. Nodakenin inhibited the mRNA expression and production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß in PMACI-stimulated HMC-1. We also studied the inhibitory effects of nodakenin on the nuclear translocation of nuclear factor kappa B (NF-κB) and activation of caspase-1, inhibitory κB kinase (IKK), and Akt in PMACI-stimulated HMC-1. However, mitogen-activated protein kinase (MAPK) activation was not sufficient to abrogate the stimulus. In addition, administration of nodakenin at 20 mg/kg inhibited histamine release and protected mice against compound 48/80-induced anaphylactic mortality. Furthermore, Nodakenin inhibited the mRNA expression and production of pro-inflammatory cytokines and caspase-1 activation in compound 48/80-induced anaphylactic mice. These results suggest new insight that nodakenin may be a promising antiallergic related inflammatory agent for inflammatory disorders. J. Cell. Biochem. 118: 3993-4001, 2017. © 2017 Wiley Periodicals, Inc.

The alteration of serine transporter activity in a cell line model of amyotrophic lateral sclerosis (ALS).

The alteration of d-serine levels is associated with the pathogenesis of sporadic ALS and mutant SOD1 (G93A) animal model of ALS. However, the exact mechanism of d-serine transport is not known in ALS. To better understand the distribution of d-serine in ALS, we determined the activity and the expression of serine transporter in a motor neuronal cell line model of ALS (NSC-34/hSOD1G93A cells). The uptake of [3H]d-serine was significantly lower in NSC-34/hSOD1G93A cells than in control NSC-34 and NSC-34/hSOD1wt cells. In contrast, the uptake of [3H]l-serine, precursor of d-serine, was markedly increased in NSC-34/hSOD1G93A cells compared to control NSC-34 and NSC-34/hSOD1wt cells. Both [3H]d-serine and [3H]l-serine uptake were saturable in these cells. The estimated Michaelis-Menten constant, Km, for d-serine uptakes was higher in NSC-34/hSOD1G93A cells than in NSC-34/hSOD1wt cells while the Km for l-serine uptake was 2 fold lower in NSC-34/hSOD1G93A cells than in control cells. [3H]d-serine and [3H]l-serine uptakes took place in a Na+-dependent manner, and both uptakes were significantly inhibited by system ASC (alanine-serine-cysteine) substrates. As a result of small interfering RNA experiments, we found that ASCT2 (SLC1A5) and ASCT1 (SLC1A4) are involved in [3H]d-serine and [3H]l-serine uptake in NSC-34/hSOD1G93A cells, respectively. The level of SLC1A4 mRNA was significantly increased in NSC-34/hSOD1G93A compared to NSC-34 and NSC-34/hSOD1wt cells. In contrast, the level of SLC7A10 mRNA was relatively lower in NSC-34/hSOD1G93A cells than the control cells. Together, these data suggest that the pathological alteration of d- and l-serine uptakes in ALS is driven by the affinity change of d-and l-serine uptake system.

Taurine Protects Glutamate Neurotoxicity in Motor Neuron Cells.

Amyotrophic lateral sclerosis (ALS) is a fetal neurodegenerative disease that results in motor dysfunction and death. However, there is no cure or effective therapy for ALS. In our previous results, taurine protects motor neurons by repairing for constitutive oxidative stress in an ALS model. ALS is caused by multiple factors including inflammation, oxidative stress, mitochondrial dysfunction, apoptosis, glutamate excitotoxicity and proteasomal dysfunction. Especially, glutamate excitotoxicity has been well known as a mediator in the disease process, and may occur from changes in the excitability of the neurons being stimulated. D-serine is known to a key factor of determination on glutamate toxicity in ALS. Therefore, in the present study, we investigated neuroprotective effects of taurine from glutamate excitotoxicity using motor neuron cells, mtSOD1 (G93A) transgenic cell line model of ALS (NSC-34/hSOD1G93A cells). We evidenced that taurine protects cultured motor neurons from neurotoxic injury. Our findings indicated that taurine has neuroprotective properties and may be a good candidate for therapeutic trials in ALS.

Changes in microbial composition and the prevalence of foodborne pathogens in crab marinated in soy sauce produced by six manufacturing plants.

BACKGROUND: The present study examined the changes in microbiological composition during the production process of crab marinated in soy sauce, potential microbial hazards, potential contamination routes and effective critical control points. Crab and soy sauce samples were obtained from six different manufacturing plants at different stages, and their microbiological content was comprehensively assessed by quantitative and qualitative analyses. RESULTS: The results revealed the following: (1) the final products contained 4.0 log colony-forming units (CFU) g-1 aerobic plate counts (APCs) and 1.1 log CFU g-1 coliforms, which may have been introduced from the raw materials (the level of APCs in raw crab and soy sauce mixed with other ingredients was 3.8 log CFU g-1 and 4.0 log CFU mL-1 respectively); (2) marination of crab in soy sauce may allow cross-contamination by coliforms; (3) only Bacillus cereus and Staphylococcus aureus were qualitatively detected in samples at different stages of manufacture (detection rate of 28 and 5.6% respectively), and these bacteria may impact the microbiological quality and safety of crab marinated in soy sauce; and (4) bacterial counts were either maintained or increased during the manufacturing process (suggesting that no particular step can be targeted to reduce bacterial counts). CONCLUSION: Proper management of raw materials and the marination process are effective critical control points, and alternative interventions may be needed to control bacterial quantity. The results provide important basic information about the production of crab marinated in soy sauce and may facilitate effective implementation of sanitary management practices in related industries and research fields. © 2016 Society of Chemical Industry.

In Vivo and In Vitro Evidence for Brain Uptake of 4-Phenylbutyrate by the Monocarboxylate Transporter 1 (MCT1).

PURPOSE: 4-Phenylbutyrate (4-PBA) is expected to be a potential therapeutic for several neurodegenerative diseases. These activities require 4-PBA transport into the brain across the blood-brain barrier (BBB). The objective of the present study was to characterize the brain transport mechanism of 4-PBA through the BBB. METHODS: The brain transport of 4-PBA across the BBB was investigated following intravenous (IV) injection and internal carotid artery perfusion (ICAP) in vivo. The mechanism of transport was examined using TR-BBB cells, an in vitro model of the BBB. RESULTS: The volume of distribution (VD) of 4-PBA by rat brain was about 7-fold greater than that of sucrose, a BBB impermeable vascular space marker, suggesting the blood-to-brain transport of 4-PBA through the BBB in the physiological state. [(14)C]4-PBA uptake by TR-BBB cells showed time-, pH- and concentration-dependence with a K m of 13.4 mM at pH 7.4 and 3.22 mM at pH 6.0. The uptake was Na(+) independent, and was significantly inhibited by alpha-cyano-4-hydroxycinnamate (a typical inhibitor for monocarboxylate transport), endogenous monocarboxylate compounds and monocarboxylic drugs. Lactate and valproate competitively inhibited [(14)C]4-PBA uptake with K i value of 13.5 mM and 7.47 mM, respectively. These results indicate the role of monocarboxylate transporters (MCTs) in 4-PBA transport into the brain at the BBB. TR-BBB cells expressed mRNA of rMCT1, 2, and 4, especially, rMCT1 showed high mRNA expression level. In addition, [(14)C]4-PBA uptake was inhibited by rMCT1 specific small interfering RNA. CONCLUSION: The transport mechanism of 4-PBA from blood to brain across the BBB likely involves MCT1.

Comparison of sensory tests and neuronal quantity of peripheral nerves between streptozotocin (STZ)-induced diabetic rats and paclitaxel (PAC)-treated rats.

Although diabetic peripheral neuropathy (DPN) and chemotherapy-induced peripheral neuropathy (CIPN) are different disease entities, they share similar neuropathic symptoms that impede quality of life for these patients. Despite having very similar downstream effects, there have been no direct comparisons between DPN and CIPN with respect to symptom severity and therapeutic responses. We compared peripheral nerve damage due to hyperglycemia with that caused by paclitaxel (PAC) treatment as represented by biochemical parameters, diverse sensory tests, and immunohistochemistry of cutaneous and sciatic nerves. The therapeutic effects of alpha-lipoic acid and DA-9801 were also compared in the two models. Animals were divided into seven groups (n = 7-10) as follows: normal, diabetes (DM), DM + alpha-lipoic acid 100 mg/kg (ALA), DM + DA-9801 (100 mg/kg), paclitaxel-treated rat (PAC), PAC + ALA (100 mg/kg), and PAC + DA-9801 (100 mg/kg). The sensory thresholds of animals to mechanical, heat, and pressure stimuli were altered by both hyperglycemia and PAC when compared with controls, and the responses to sensory tests were different between both groups. There were no significant differences in the biochemical markers of blood glutathione between DM and PAC groups (p > .05). Quantitative comparisons of peripheral nerves by intraepidermal nerve fiber density (IENFD) analysis indicated that the DM and PAC groups were similar (6.18 ± 1.03 vs. 5.01 ± 2.57). IENFD was significantly improved after ALA and DA-9801 treatment in diabetic animals (7.6 ± 1.28, 7.7 ± 1.28, respectively, p < .05) but did not reach significance in the PAC-treated groups (6.05 ± 1.76, 5.66 ± 1.26, respectively, p > .05). Sciatic nerves were less damaged in the PAC-treated groups compared with the DM groups with respect to axonal diameter and area (8.60 ± 1.14 µm vs. 6.66 ± 1.07 µm, and 59.04 ± 15.16 µm2 vs. 35.71 ± 11.2 µm2, respectively, p < .05). Based on these results, the neuropathic manifestation and therapeutic responses of DPN may be different from other peripheral neuropathies. Therefore, specific pathogenic consideration according to peripheral neuropathy classification in addition to common treatments needs to be developed for management strategies of peripheral neuropathies.

Anti-Proliferation Effects of Garlic (Allium sativum L.) on the Progression of Benign Prostatic Hyperplasia.

Benign prostatic hyperplasia (BPH) is a urologic disease that affects most of men over the age 50. But until now there is no such perfect cure without side effects. Because of diverse adverse effects, it is desirable to develop effective and long term-safety-herbal medicines to inhibit the progress of BPH. In spite of garlic's large use and a wide spectrum of studies, including anti-hyperlipidemic, cardio-protective, and anti-inflammatory activities, there was none to prove efficacy for BPH. In this study, we evaluated the efficacy of garlic to prove its suppressing effects on BPH. Garlic administration decreased relative prostate weight ratio, suppressed mRNA expression level of AR, DHT serum levels, and the growth of prostatic tissue in BPH-induced rats. Moreover, garlic administration decreased the levels of inflammatory proteins, iNOS, and COX-2 in prostatic tissue. Further investigation showed that garlic induced accumulation of death-inducing signal complex and activation of AMPK and decreased the levels of anti-apoptotic proteins, such as Bcl-2, Bcl-xL, and survivin. These results suggest that garlic may have suppressing effects on BPH and it has great potential to be developed as treatment for BPH. Copyright © 2016 John Wiley & Sons, Ltd.

Analysis of nitrated proteins in Saccharomyces cerevisiae involved in mating signal transduction.

Protein tyrosine nitration (PTN) is a PTM that regulates signal transduction and inflammatory responses, and is related to neurodegenerative and cardiovascular diseases. The cellular function of PTN remains unclear because the low stoichiometry of PTN limits the identification and quantification of nitrated peptides. Effective enrichment is an important aspect of PTN analysis. In this study, we analyzed the in vivo nitroproteome elicited by mating signal transduction in Saccharomyces cerevisiae using a novel chemical enrichment method followed by LC-MS/MS. Nitroproteome profiling successfully identified changes in the nitration states of 14 proteins during mating signal transduction in S. cerevisiae, making this the first reported in vivo nitroproteome in yeast. We investigated the biological functions of these nitroproteins and their relationships to mating signal transduction in S. cerevisiae using a protein-protein interaction network. Our results suggest that PTN and denitration may be involved in nonreactive nitrogen species-mediated signal transduction and can provide clues for understanding the functional roles of PTN in vivo.

Effect of Chicoric Acid on Mast Cell-Mediated Allergic Inflammation in Vitro and in Vivo.

Chicoric acid (dicaffeoyl-tartaric acid), is a natural phenolic compound found in a number of plants, such as chicory (Cichorium intybus) and Echinacea (Echinacea purpurea), which possesses antioxidant, anti-inflammatory, antiviral, and analgesic activities. Although these biological effects of chicoric acid have been investigated, there are no reports of its antiallergic-related anti-inflammatory effects in human mast cells (HMC)-1 or anaphylactic activity in a mouse model. Therefore, we investigated the antiallergic-related anti-inflammatory effect of chicoric acid and its underlying mechanisms of action using phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated HMC-1 cells. Chicoric acid decreased the mRNA expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß. We studied the inhibitory effects of chicoric acid on the nuclear translocation of nuclear factor kappa B (NF-κB) and activation of caspase-1. However, mitogen-activated protein kinase (MAPK) activation was not sufficient to abrogate the stimulus. In addition, we investigated the ability of chicoric acid to inhibit compound 48/80-induced systemic anaphylaxis in vivo. Oral administration of chicoric acid at 20 mg/kg inhibited histamine release and protected mice against compound 48/80-induced anaphylactic mortality. These results suggest that chicoric acid has an antiallergic-related anti-inflammatory effect that involves modulating mast cell-mediated allergic responses. Therefore, chicoric acid could be an efficacious agent for allergy-related inflammatory disorders.

Synergistic effects of ultrasound and sodium hypochlorite (NaOCl) on reducing Listeria monocytogenes ATCC19118 in broth, stainless steel, and iceberg lettuce.

This study was performed in order to determine whether a combined treatment of ultrasound and sodium hypochlorite (NaOCl) is more effective than individual treatment on reducing Listeria monocytogenes ATCC19118 on stainless steel and iceberg lettuce. The bactericidal effect of ultrasound and NaOCl was investigated in tryptic soy broth (TSB), on stainless steel and iceberg lettuce. Various concentrations of NaOCl (50, 100, 150, and 200 ppm) were tested along with various ultrasound treatment times (5, 20, 40, 60, 80, and 100 min). The combined treatment of ultrasound and NaOCl resulted in greater bacterial reductions than either treatment alone, without causing any significant changes in lettuce texture. The synergistic values of combined ultrasound and NaOCl treatments in TSB, on stainless steel, and on iceberg lettuce were 0.01-0.99 log10 colony-forming units (CFU)/mL, 0.01-0.62 log 10 CFU/g, and 0.12-1.66 log10 CFU/g, respectively. These results suggest that the combination of ultrasound and NaOCl was more effective than each treatment against Listeria monocytogenes, and that this combination can effectively sanitize fresh products such as iceberg lettuce.

Characteristic Differences between Normotensive and Hypertensive Pseudoexfoliative Glaucoma.

PURPOSE: To compare the differences between eyes with pseudoexfoliative glaucoma (PXG) when they are divided into two groups (hypertensive PXG and normotensive PXG) according to the intraocular pressure (IOP). METHODS: This is a retrospective study. Data from 86 hypertensive PXG eyes and 80 normotensive PXG eyes were included. Hypertensive PXG was defined as PXG with IOP ≥ 22 mmHg, and normotensive PXG was defined as with IOP ≤ 21 mmHg). Central corneal thickness (CCT) was measured by ultrasound pachymetry. Lamina cribrosa thickness (LT) was evaluated using swept-source optical coherence tomography. RESULTS: No significant differences were observed between hypertensive and normotensive PXG in terms of age, gender, axial length, hypertension, or diabetes. Normotensive PXG eyes had thinner CCT than hypertensive PXG eyes (p = 0.02). To compare LT, a sub-analysis was performed after matching age, VF MD and retinal nerve fiber layer thickness. The normotensive PXG group (n = 32) demonstrated significantly thinner LT compared with the hypertensive PXG group (n = 32) at similar ages and levels of glaucoma severity (p < 0.001). CONCLUSIONS: Eyes with normotensive PXG demonstrated thinner CCT and LT compared with those with hypertensive PXG, suggesting structural vulnerability to glaucoma.

Interplay between YAP/TAZ and metabolic dysfunction-associated steatotic liver disease progression.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming an increasingly pressing global health challenge, with increasing mortality rates showing an upward trend. Two million deaths occur annually from cirrhosis and liver cancer together each year. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), key effectors of the Hippo signaling pathway, critically regulate tissue homeostasis and disease progression in the liver. While initial studies have shown that YAP expression is normally restricted to cholangiocytes in healthy livers, the activation of YAP/TAZ is observed in other hepatic cells during chronic liver disease. The disease-driven dysregulation of YAP/TAZ appears to be a critical element in the MASLD progression, contributing to hepatocyte dysfunction, inflammation, and fibrosis. In this study, we focused on the complex roles of YAP/TAZ in MASLD and explored how the YAP/TAZ dysregulation of YAP/TAZ drives steatosis, inflammation, fibrosis, and cirrhosis. Finally, the cell-type-specific functions of YAP/TAZ in different types of hepatic cells, such as hepatocytes, hepatic stellate cells, hepatic macrophages, and biliary epithelial cells are discussed, highlighting the multifaceted impact of YAP/TAZ on liver physiology and pathology.