Two-motif model illuminates DICER cleavage preferences.

In humans, DICER is a key regulator of gene expression through its production of miRNAs and siRNAs by processing miRNA precursors (pre-miRNAs), short-hairpin RNAs (shRNAs), and long double-stranded RNAs (dsRNAs). To advance our understanding of this process, we employed high-throughput dicing assays using various shRNA variants and both wild-type and mutant DICER. Our analysis revealed that DICER predominantly cleaves shRNAs at two positions, specifically at 21 (DC21) and 22 (DC22) nucleotides from their 5'-end. Our investigation identified two different motifs, mWCU and YCR, that determine whether DICER cleaves at DC21 or DC22, depending on their locations in shRNAs/pre-miRNAs. These motifs can work together or independently to determine the cleavage sites of DICER. Furthermore, our findings indicate that dsRNA-binding domain (dsRBD) of DICER enhances its cleavage, and mWCU strengthens the interaction between dsRBD and RNA, leading to an even greater enhancement of the cleavage. Conversely, YCR functions independently of dsRBD. Our study proposes a two-motif model that sheds light on the intricate regulatory mechanisms involved in gene expression by elucidating how DICER recognizes its substrates, providing valuable insights into this critical biological process.

Nanosecond Transient IR Spectroscopy of Halorhodopsin in Living Cells.

The ability to track minute changes of a single amino acid residue in a cellular environment is causing a paradigm shift in the attempt to fully understand the responses of biomolecules that are highly sensitive to their environment. Detecting early protein dynamics in living cells is crucial to understanding their mechanisms, such as those of photosynthetic proteins. Here, we elucidate the light response of the microbial chloride pump NmHR from the marine bacterium Nonlabens marinus, located in the membrane of living Escherichia coli cells, using nanosecond time-resolved UV/vis and IR absorption spectroscopy over the time range from nanoseconds to seconds. Transient structural changes of the retinal cofactor and the surrounding apoprotein are recorded using light-induced time-resolved UV/vis and IR difference spectroscopy. Of particular note, we have resolved the kinetics of the transient deprotonation of a single cysteine residue during the photocycle of NmHR out of the manifold of molecular vibrations of the cells. These findings are of high general relevance, given the successful development of optogenetic tools from photoreceptors to interfere with enzymatic and neuronal pathways in living organisms using light pulses as a noninvasive trigger.

Intramolecular ligation method (iLIME) for pre-miRNA quantification and sequencing.

Hairpin-containing pre-miRNAs, produced from pri-miRNAs, are precursors of miRNAs (microRNAs) that play essential roles in gene expression and various human diseases. Current qPCR-based methods used to quantify pre-miRNAs are not effective to discriminate between pre-miRNAs and their parental pri-miRNAs. Here, we developed the intramolecular ligation method (iLIME) to quantify and sequence pre-miRNAs specifically. This method utilizes T4 RNA ligase 1 to convert pre-miRNAs into circularized RNAs, allowing us to design PCR primers to quantify pre-miRNAs, but not their parental pri-miRNAs. In addition, the iLIME also enables us to sequence the ends of pre-miRNAs using next-generation sequencing. Therefore, this method offers a simple and effective way to quantify and sequence pre-miRNAs, so it will be highly beneficial for investigating pre-miRNAs when addressing research questions and medical applications.

Predicting drought stress under climate change in the Southern Central Highlands of Vietnam.

In the Southern Central Highlands of Vietnam, droughts occur more frequently, causing significant damage and impacting the region's socio-economic development. During the dry season, rivers, streams, and reservoirs often face limited water availability, exacerbated in recent years by increasing drought severity. Recognizing the escalating severity of droughts, the study offers a novel contribution by conducting a comprehensive analysis of surface water resource distribution in Lam Dong province, focusing on assessing water demand for agricultural production, a crucial factor in ensuring sustainable crop growth. Two scenarios, Current-2020 (SC1) and Climate Change-2025 (SC2), are simulated, with SC2 based on climate change and sea level rise scenarios provided by the Ministry of Natural Resources and Environment (MONRE). These scenarios are integrated into the MIKE-NAM and MIKE-HYDRO basin models, allowing for a thorough assessment of the water balance of Lam Dong province. Furthermore, the study utilizes the Keetch-Byram Drought Index (KBDI) to measure drought severity, revealing prevalent dry and moderately droughty conditions in highland districts with rainfall frequency ranging from 50 to 85%. Severe drought conditions occur with a rainfall frequency of 95%, indicating an increased frequency and geographic scope of severe droughts. Additionally, the study highlights that under abnormally dry conditions, water demand for the winter-spring crop is consistently met at 100%, decreasing to 85%, 80%, and less than 75% for moderate, severe, and extreme droughts, respectively. These findings offer insights into future drought conditions in the Lam Dong province and their potential impact on irrigation capacity, crucial for adaptation strategies.

Applications of artificial intelligence for patients with peripheral artery disease.

OBJECTIVE: Applications of artificial intelligence (AI) have been reported in several cardiovascular diseases but its interest in patients with peripheral artery disease (PAD) has been so far less reported. The aim of this review was to summarize current knowledge on applications of AI in patients with PAD, to discuss current limits, and highlight perspectives in the field. METHODS: We performed a narrative review based on studies reporting applications of AI in patients with PAD. The MEDLINE database was independently searched by two authors using a combination of keywords to identify studies published between January 1995 and December 2021. Three main fields of AI were investigated including natural language processing (NLP), computer vision and machine learning (ML). RESULTS: NLP and ML brought new tools to improve the screening, the diagnosis and classification of the severity of PAD. ML was also used to develop predictive models to better assess the prognosis of patients and develop real-time prediction models to support clinical decision-making. Studies related to computer vision mainly aimed at creating automatic detection and characterization of arterial lesions based on Doppler ultrasound examination or computed tomography angiography. Such tools could help to improve screening programs, enhance diagnosis, facilitate presurgical planning, and improve clinical workflow. CONCLUSIONS: AI offers various applications to support and likely improve the management of patients with PAD. Further research efforts are needed to validate such applications and investigate their accuracy and safety in large multinational cohorts before their implementation in daily clinical practice.

Adsorption and photodegradation of micropollutant in wastewater by photocatalyst TiO2/rice husk biochar.

With the acceleration of global industrialization, organic pollutants have become a threat to ecological safety and human health. This work prepared TiO2/rice husk biochar (TiO2/BC) for removal of bisphenol A (BA) micropollutant in wastewater. Experiment results revealed a low BA removal efficiency by TiO2/BC was observed at 34.5% under the dark environment. However, the removal rate of BA by UV light-assisted TiO2/BC significantly increased to 97.6% in 1 h. The results also demonstrated that the removal performance of BA using TiO2/BC was 2.1times higher than that of commercial TiO2 (46.4%). Besides, the removal efficiency of BA by reused TiO2/BC after eight cycles slightly decreased by 12.8%, demonstrating the excellent properties of the prepared composite. TiO2/BC also exhibited high removal efficiency of BA (over 89%) from the synthetic wastewater sample, indicating the potential utilization of composite for removing BA in wastewater. This work provides a new way to turn biomass waste into useful material and effective method to remove micropollutant BA.

Two trehalase isoforms, produced from a single transcript, regulate drought stress tolerance in Arabidopsis thaliana.

KEY MESSAGE: Alternative translation initiation of the unique Arabidopsis trehalase gene allows for the production of two isoforms with different subcellular localization, providing enzyme access to both intra- and extra-cellular trehalose. The trehalose-hydrolyzing enzyme trehalase mediates drought stress tolerance in Arabidopsis thaliana by controlling ABA-induced stomatal closure. We now report the existence of two trehalase isoforms, produced from a single transcript by alternative translation initiation. The longer full-length N-glycosylated isoform (AtTRE1L) localizes in the plasma membrane with the catalytic domain in the apoplast. The shorter isoform (AtTRE1S) lacks the transmembrane domain and localizes in the cytoplasm and nucleus. The two isoforms can physically interact and this interaction affects localization of AtTRE1S. Consistent with their role in plant drought stress tolerance, both isoforms are activated by AtCPK10, a stress-induced calcium-dependent guard cell protein kinase. Transgenic plants expressing either isoform indicate that both can mediate ABA-induced stomatal closure in response to drought stress but that the short (cytoplasmic/nuclear) isoform, enriched in those conditions, is significantly more effective.

Human disease-associated single nucleotide polymorphism changes the orientation of DROSHA on pri-mir-146a.

The Microprocessor complex of DROSHA and DGCR8 initiates the biosynthesis of microRNAs (miRNAs) by processing primary miRNAs (pri-miRNAs). The Microprocessor can be oriented on pri-miRNAs in opposite directions to generate productive and unproductive cleavages at their basal and apical junctions, respectively. However, only the productive cleavage gives rise to miRNAs. A single nucleotide polymorphism (SNP, rs2910164) in pri-mir-146a is associated with various human diseases. Although this SNP was found to reduce the expression of miRNA, it is still not known if it affects the activity of the Microprocessor directly, and how it functions. In this study, we revealed that the SNP creates an unexpected mGHG motif at the apical junction of pri-mir-146a. This mGHG motif interacts with the double-stranded RNA-binding domain (dsRBD) of DROSHA, switching its orientation on pri-mir-146a from the basal to the apical junction. As a result, the SNP facilitates Microprocessor to cleave SNP-pri-mir-146a at its unproductive sites. Our findings help to elucidate the molecular mechanism that explains how the disease-associated SNP modulates the biogenesis of pri-mir-146a and thereby affects its cellular functions.

Automatic Measurement of Vascular Calcifications in Patients with Aorto-Iliac Occlusive Disease to Predict the Risk of Re-intervention After Endovascular Repair.

BACKGROUND: There is currently a lack of consensus and tools to easily measure vascular calcification using computed tomography angiography (CTA). The aim of this study was to develop a fully automatic software to measure calcifications and to evaluate the interest as predictive factor in patients with aorto-iliac occlusive disease. METHODS: This study retrospectively included 171 patients who had endovascular repair of an aorto-iliac occlusive lesion at the University Hospital of Nice between January 2011 and December 2019. Calcifications volumes were measured from CTA using an automatic method consisting in three sequential steps: image pre-processing, lumen segmentation using expert system, and deep learning algorithms and segmentation of calcifications. Calcification volumes were measured in the infrarenal abdominal aorta and the iliac arterial segments, corresponding to the common and the external iliac arteries. RESULTS: Among 171 patients included with a mean age of 65 years, the revascularization was performed on the native external and internal iliac arteries in, respectively: 83 patients (48.5%), 107 (62.3%), and 7 (4.1%). The mean volumes of calcifications were 2,759 mm3 in the infrarenal abdominal aorta, 1,821 mm3 and 1,795 mm3 in the right and left iliac arteries, respectively. For a mean follow-up of 39 months, target lesion re-intervention was performed in 55 patients (32.2%). These patients had higher volume of calcifications in the right and left iliac arteries, compared with patients who did not have a re-intervention (2,274 mm3 vs. 1,606 mm3, P = 0.0319 and 2,278 vs. 1,567 mm3, P = 0.0213). CONCLUSIONS: The development of a fully automatic software would be useful to facilitate the measurement of vascular calcifications and possibly better inform the prognosis of patients.

Automatic Measurement of Maximal Diameter of Abdominal Aortic Aneurysm on Computed Tomography Angiography Using Artificial Intelligence.

INTRODUCTION: The treatment of abdominal aortic aneurysm relies on surgical repair and the indication mainly depends on its size evaluated by the maximal diameter (Dmax). The aim of this study was to evaluate a new automatic method based on artificial intelligence to measure the Dmax on computed tomography angiography. METHODS: A fully automatic segmentation of the vascular system was performed using a hybrid method combining expert system with supervised deep learning. The aorta centreline was extracted from the segmented aorta and the aortic diameters were automatically calculated. Results were compared to manual segmentation performed by two human operators. RESULTS: The median absolute error between the two human operators was 1.2 mm (IQR 0.5-1.9). The automatic method using the deep learning algorithm demonstrated correlation with the human segmentation, with a median absolute error of 0.8 (0.5-4.2) mm and a coefficient correlation of 0.91 (P < 0.001). CONCLUSIONS: Although validation in larger cohorts is required, this method brings perspectives to develop new tools to standardize and automate the measurement of abdominal aortic aneurysm Dmax in order to help clinicians in the decision-making process.

Incidence of contrast-induced acute kidney injury in patients with acute mesenteric ischemia and identification of potential predictive factors.

OBJECTIVE: Contrast-enhanced computed tomography angiography (CTA) is commonly used to investigate acute abdominal conditions, but the risk of contrast-induced acute kidney injury (CI-AKI) has been poorly investigated in patients with acute mesenteric ischemia. The aim of the present study was to evaluate the incidence of CI-AKI in these patients and identify potential predictive factors. METHODS: Patients admitted for acute mesenteric ischemia who had a diagnostic CTA with contrast medium and a follow-up of creatinine concentration were retrospectively included. RESULTS: Among 53 patients included, 9 (16.9%) developed CI-AKI. The prevalence of chronic kidney disease did not differ significantly between those who developed CI-AKI and those who did not (33.3 vs 18.2%, p=.372). Plasma total bilirubin and conjugated bilirubin levels were significantly higher in patients who developed CI-AKI (17.5 vs 8.0 µmol/L, p=.013 and 8.0 vs 3.0 µmol/L, p=.031, respectively). The proportion of patients who had revascularization was similar between patients who developed CI-AKI and those who did not (11.1 vs 20.5%, p>.999). No significant difference was observed for 30-day mortality and all-cause mortality for a median follow-up of 168 days (22.2 vs 13.6%, p=.611; and 33.3 vs 61.4%, p=.153, respectively). CONCLUSION: This study reports the incidence of CI-AKI in patients with acute mesenteric ischemia after diagnostic CTA with contrast medium. Plasma bilirubin levels were a predictive factor of CI-AKI in these patients. The administration of contrast media during revascularization was not associated with an increased risk of CI-AKI.

Global microRNA depletion suppresses tumor angiogenesis.

MicroRNAs delicately regulate the balance of angiogenesis. Here we show that depletion of all microRNAs suppresses tumor angiogenesis. We generated microRNA-deficient tumors by knocking out Dicer1. These tumors are highly hypoxic but poorly vascularized, suggestive of deficient angiogenesis signaling. Expression profiling revealed that angiogenesis genes were significantly down-regulated as a result of the microRNA deficiency. Factor inhibiting hypoxia-inducible factor 1 (HIF-1), FIH1, is derepressed under these conditions and suppresses HIF transcription. Knocking out FIH1 using CRISPR/Cas9-mediated genome engineering reversed the phenotypes of microRNA-deficient cells in HIF transcriptional activity, VEGF production, tumor hypoxia, and tumor angiogenesis. Using multiplexed CRISPR/Cas9, we deleted regions in FIH1 3' untranslated regions (UTRs) that contain microRNA-binding sites, which derepresses FIH1 protein and represses hypoxia response. These data suggest that microRNAs promote tumor responses to hypoxia and angiogenesis by repressing FIH1.

Psychotropic Drugs Prescription and Use among Children with Mental Disorders at a Tertiary Hospital in Vietnam.

Background: Awareness of psychotropic medication and its adverse drug reactions (ADRs) can promote safe and rational use of medications, particularly in children and adolescents with mental problems. This study examined the prescription of psychotropic drugs and actual drug-drug interaction (DDI) and ADR for children with mental disorders under 18 years of age in a tertiary hospital in Vietnam. Methods: A cross-sectional descriptive study was performed on 257 psychiatric inpatients under 18 years of age at the National Mental Health Institute-Bach Mai Hospital in 2017. Information about the course of treatment included prescribed medications, drug interactions, side effects, drug combination, and modifications to the regimen was collected. Results: 14.8% and 59.5% of patients received a single-drug regimen and a 2-drug combination regimen upon admission, respectively. The most used regimen was antipsychotics + tranquilizers, accounting for 38.1%. Haloperidol was the most commonly prescribed drug (40.5%). Most patients were given the recommended dosage of the drug (>90%). There were 20.6% of patients having drug interactions with the largest proportion of the combination of diazepam and olanzapine (62.3%). ADRs of psychotropic drugs were detected in 46.3% of patients, with the highest rate of ADRs from antipsychotic drugs. Antipsychotics had the highest rate of replacement (91.3%), mostly replaced from a first-generation antipsychotic (FGA) to a second-generation antipsychotic (SGA). Conclusion: The appointment of psychotropic drugs to patients under 18 years of age has to comply with the recommendations, and carefully balance the benefits and risks of ADRs as well as the risk of DDI in case of the drug combination.

Design, synthesis, and evaluation of novel N'-substituted-1-(4-chlorobenzyl)-1H-indol-3-carbohydrazides as antitumor agents.

In continuity of our search for novel anticancer agents acting as procaspase activators, we have designed and synthesised two series of (E)-N'-benzylidene-carbohydrazides (4a-m) and (Z)-N'-(2-oxoindolin-3-ylidene)carbohydrazides (5a-g) incorporating 1-(4-chlorobenzyl)-1H-indole core. Bioevaluation showed that the compounds, especially compounds in series 4a-m, exhibited potent cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer). Within series 4a-m, compounds with 2-OH substituent (4g-i) exhibited very strong cytotoxicity in three human cancer cell lines assayed with IC50 values in the range of 0.56-0.83 µM. In particular, two compounds 4d and 4f bearing 4-Cl and 4-NO2 substituents, respectively, were the most potent in term of cytotoxicity with IC50 values of 0.011-0.001 µM. In caspase activation assay, compounds 4b and 4f were found to activate caspase activity by 314.3 and 270.7% relative to PAC-1. This investigation has demonstrated the potential of these simple acetohydrazides, especially compounds 4b, 4d, and 4f, as anticancer agents.

New Acetohydrazides Incorporating 2-Oxoindoline and 4-Oxoquinazoline: Synthesis and Evaluation of Cytotoxicity and Caspase Activation Activity.

In our search for new small molecules activating procaspase-3, we have designed and synthesized a series of new acetohydrazides incorporating both 2-oxoindoline and 4-oxoquinazoline scaffolds. Biological evaluation showed that a number of these acetohydrazides were comparably or even more cytotoxic against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer) in comparison to PAC-1, a first procaspase-3 activating compound, which was used as a positive control. One of those new compounds, 2-(6-chloro-4-oxoquinazolin-3(4H)-yl)-N'-[(3Z)-5-methyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene]acetohydrazide activated the caspase-3 activity in U937 human lymphoma cells by 5-fold higher than the untreated control. Three of the new compounds significantly induced necrosis and apoptosis in U937 cells.

Accumulation rates of natural radionuclides (40K, 210Pb, 226Ra, 238U, and 232Th) in topsoils due to long-term cultivations of water spinach (Ipomoea Aquatica Forssk.) and rice (Oryza Sativa L.) based on model assessments: A case study in Dong Nai province, Vietnam.

In topsoils, the activity concentrations of natural radionuclides (hereafter NRs) increase due to the addition of NRs from fertilizers, irrigation water, and air dust pollution. On the other hand, various physical-chemical and environmental processes such as radioactive decay, volatilization, leaching, erosion, and plant uptake were responsible for the decrease of the activity concentrations of NRs in the topsoils. In this study, behaviours of 40K, 210Pb, 226Ra, 238U, and 232Th in topsoils were modelled by the CEMC soil model and the HYDRUS-1D model. An exponential equation was proposed for estimating the accumulation rates of these radionuclides in the topsoils. Long-term accumulation of radionuclides was assessed for water spinach (Ipomoea Aquatica Forssk.) soil (hereafter VES) and rice (Oryza sativa L.) soil (hereafter RIS). We found that the current agricultural practices caused the increase of 40K activity concentration in the water spinach soil, and 40K, 210Pb, 226Ra, and 232Th activity concentrations in the rice soil. The accumulation rates of radionuclides were in the order 238U < 232Th < 226Ra < 210Pb < 40K. 25 years of cultivation with water spinach can increase/decrease + (165 ± 6) Bq of 40K, - (8.2 ± 0.7) Bq of 210Pb, - (4.3 ± 0.2) Bq of 226Ra, - (7 0.3 ± 0.3) Bq of 238U, and - (1.8 ± 0.1) Bq of 232Th in 1 kg soil. For rice cultivation, these values are + (1004 ± 39), + (3.3 ± 0.2), + (3.0 ± 0.2), - (5.1 ± 0.3), (2.2 ± 0.1) Bq kg-1 for 40K, 210Pb, 226Ra, 238U, and 232Th, respectively.

Novel 3,4-dihydro-4-oxoquinazoline-based acetohydrazides: Design, synthesis and evaluation of antitumor cytotoxicity and caspase activation activity.

In search for novel small molecules with antitumor cytotoxicity via activating procaspase-3, we have designed and synthesized three series of novel (E)-N'-benzylidene-4-oxoquinazolin-3(4H)-yl)acetohydrazides (5a-j, 6a-h, and 7a-h). On the phenyl ring ò the benzylidene part, three different substituents, including 2-OH-4-OCH3, 4-OCH3, and 4-N(CH3)2, were introduced, respectively. Biological evaluation showed that the acetohydrazides in series 5a-j, in which the phenyl ring of the benzylidene part was substituted by 2-OH-4-OCH3 substituent, exhibited potent cytotoxicity against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung). Most of the compounds, in this series, especially compounds 5c, 5b and 5h, also significantly activated caspase-3 activity. Among these, compound 5c displayed 1.61-fold more potent than PAC-1 as caspase-3 activator. Cell cycle analysis showed that compounds 5b, 5c, and 5h significantly arrested the cell cycle in G1 phase. Further apoptotic studies also demonstrated compounds 5b, 5c, and 5h as strong apoptotic cell death inducers. The docking simulation studies showed that these compounds could activate procaspase via chelating Zn2+ ion bound to the allosteric site of the zymogen.

(E)-N'-Arylidene-2-(4-oxoquinazolin-4(3H)-yl) acetohydrazides: Synthesis and evaluation of antitumor cytotoxicity and caspase activation activity.

In our search for novel small molecules activating procaspase-3, we have designed and synthesised a series of novel acetohydrazides incorporating quinazolin-4(3H)-ones (5, 6, 7). Biological evaluation revealed eight compounds with significant cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer). The most potent compound 5t displayed cytotoxicity up to 5-fold more potent than 5-FU. Analysis of structure-activity relationships showed that the introduction of different substituents at C-6 position on the quinazolin-4(3H)-4-one moiety, such as 6-chloro or 6-methoxy potentially increased the cytotoxicity of the compounds. In term of caspase activation activity, several compounds were found to exhibit potent effects, (e.g. compounds 7 b, 5n, and 5l). Especially, compound 7 b activated caspases activity by almost 200% in comparison to that of PAC-1. Further docking simulation also revealed that this compound potentially is a potent allosteric inhibitor of procaspase-3.

Modelling the mitigation speeds of 137Cs, 90Sr and 131I in the topsoils and assessment of the radiological hazards.

Fate modelling of artificial radionuclides (ARs) in top soils are necessary to assess the radiological effects to population. Among ARs, 137Cs, 90Sr and 131I are very important since the large abundances in the environment. In this study, the fates of 137Cs, 90Sr and 131I in the surface soil layers were simulated by the soil model which was developed by the Canadian Centre for Environmental Modelling and Chemistry (CEMC). The scenario that 137Cs, 90Sr and 131I contaminated in topsoil in the exclusion of Fukushima Daiichi nuclear power plant (NPP) accident was evaluated. The results show the expected time for the minimum hazardous level of exposure. It is 115.5 days after the exposure, when the total effective dose is 1 mSv y-1 in which 0.46 mSv y-1 from ingestion and 0.54 mSv y-1 from gamma exposure. Hazard levels due to exposure progresses are varied in order gamma exposure (82.14%) > ingestion (17.47%) > inhalation (0.39%). The hazard levels from radionuclides are varied in order 137Cs (63.34%) > 131I (33.48%) > 90Sr (3.18%).

Succinate induces hepatic fibrogenesis by promoting activation, proliferation, and migration, and inhibiting apoptosis of hepatic stellate cells.

Liver fibrosis is a progressive pathological process that accompanies wound healing; however, therapeutics for reversing hepatic fibrosis are unavailable. Activation of hepatic stellate cells (HSCs) play a critical role in liver fibrosis. Recent reports showed that succinate and its receptor, G-protein coupled receptor 91 (GPR91), act as signaling molecules during the activation of HSCs. However, the role of succinate in proliferation, apoptosis, and migration of HSCs has not been studied. In this study, we determined whether succinate regulates proliferation, apoptosis, and migration of HSCs and induces liver fibrosis in a mouse model. Succinate treatment not only induced activation of HSCs, but also increased the proliferation and migration of LX-2 HSCs and inhibited apoptosis. To investigate whether succinate causes hepatic fibrosis, 100 mg/kg succinate or control PBS was administered by intraperitoneal injection to mice once a day for four weeks. There were significant molecular changes such as increased α-SMA and collagen type 1 production and increased production of inflammatory cytokines such as IL-6 and TNF-α, but not TGF-ß, in the succinate-treated group compared to the control group. However, no morphological changes were observed in Masson's trichrome staining. In conclusion, the present study demonstrated that succinate induces activation, proliferation, and migration of HSCs and attenuates apoptosis in LX-2 HSCs. Therefore, inhibition of succinate accumulation may be an effective method for reversing liver fibrosis by controlling HSC survival and growth.