Causal Association Analysis of Periodontitis and Inflammatory Bowel Disease: A Bidirectional Mendelian Randomization Study.

BACKGROUND: Periodontitis has been reported to be associated with inflammatory bowel disease (IBD), including ulcerative colitis (UC), and Crohn's disease (CD). However, the causality of these 2 diseases remains unclear. We conducted bidirectional Mendelian randomization (MR) to investigate the causal relationship between periodontitis and IBD. METHODS: We obtained the genome-wide association study (GWAS) summary data of European populations from FinnGen database (for IBD) and a published article (for periodontitis), from which independent single nucleotide polymorphisms were selected as instrumental variables. Inverse variance-weighted (IVW), MR-Egger, and weighted median (WM) methods were utilized for MR analysis. Heterogeneity or pleiotropy was detected through Cochran's Q test and MR-Egger intercept, respectively. Outlier was identified with MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) and leave-one-out analysis. All statistical analyses were performed with R 4.2.1 and the packages of TwoSampleMR version 0.5.6. RESULTS: Genetic prediction showed that periodontitis was the risk factor of UC (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.01-1.26; P = .027), rather than of CD (OR, 0.92; 95% CI, 0.74-1.15; P = .456) and IBD (OR, 0.96; 95% CI, 0.81-1.13; P = .619). To the contrary, CD, not UC or IBD, resulted in exacerbating periodontitis in terms of the results of the IVW (OR, 1.09; 95% CI, 1.01-1.17; P = .021) and WM (OR, 1.10; 95% CI, 1.01-1.20; P = .030) methods. Heterogeneity or pleiotropy was acceptable. CONCLUSIONS: Our results indicated that CD was the risk factor for periodontitis; conversely, periodontitis was responsible for the exacerbation of UC, enhancing the existence of mouth-gut axis. Patients with UC should pay more attention to periodontal health, while patients with periodontitis should actively pay close heed to intestinal health.

A bidirectional Mendelian randomization study indicated that Crohn's disease was the risk factor for periodontitis; conversely, periodontitis was responsible for the exacerbation of ulcerative colitis, enhancing the existence of the mouth-gut axis and suggesting paying attention to oral health for patients of inflammatory bowel disease.

Symptom effects and central mechanism of acupuncture in patients with functional gastrointestinal disorders: a systematic review based on fMRI studies.

BACKGROUND: Functional gastrointestinal disorders (FGIDs) are closely related to disorders of brain-gut interaction. FGIDs are the dominant disease of acupuncture treatment, which can improve the symptoms and emotional state. AIM: To evaluate the results and quality of the available clinical evidence and to summarize the central mechanism and effect of acupuncture on FGIDs. METHODS: PubMed, EMBASE, Web of science, Cochrane Library, China National Knowledge Infrastructure (CNKI) were searched by computer to collect the randomized controlled trials (RCTs), which contained central mechanisms via fMRI research of acupuncture in the treatment of FGIDs patients. The search time limit was from the establishment of the database to June 22, 2022. Two researchers independently screened the literature, extracted data, and evaluated the quality. RESULTS: Ten RCTs involving fMRI data were included in this study, including 4 Functional dyspepsia (FD) studies, 3 irritable bowel syndrome (IBS) studies, and 3 functional constipation (FC) studies. The score of improvements in both gastrointestinal symptoms and psychological symptoms showed that acupuncture could significantly improve the clinical symptoms of FGIDs patients, including abdominal pain, abdominal distension, frequency of defecation, and stool characteristics, and could relieve anxiety and depression symptoms of patients. Acupuncture could regulate brain functional connections and functional activity in FGIDs patients, mainly including insula, anterior cingulate cortex, prefrontal cortex, thalamus, hippocampus, amygdala and other brain regions. CONCLUSION: Acupuncture can improve gastrointestinal symptoms and psychological status in FGIDs patients, and regulate functional connectivity and activity of brain regions such as insula, ACC, PFC, thalamus, HIPP, amygdala, etc. These changes in brain activity may related to visceral sensation, pain regulation, emotion, but further studies of high quality are still necessary.

Slo1 deficiency impaired skeletal muscle regeneration and slow-twitch fibre formation.

BACKGROUND: It has been observed that Slo1 knockout mice have reduced motor function, and people with certain Slo1 mutations have movement problems, but there is no answer whether the movement disorder is caused by the loss of Slo1 in the nervous system, or skeletal muscle, or both. Here, to ascertain in which tissues Slo1 functions to regulate motor function and offer deeper insight in treating related movement disorder, we generated skeletal muscle-specific Slo1 knockout mice, studied the functional changes in Slo1-deficient skeletal muscle and explored the underlying mechanism. METHODS: We used skeletal muscle-specific Slo1 knockout mice (Myf5-Cre; Slo1flox/flox mice, called CKO) as in vivo models to examine the role of Slo1 in muscle growth and muscle regeneration. The forelimb grip strength test was used to assess skeletal muscle function and treadmill exhaustion test was used to test whole-body endurance. Mouse primary myoblasts derived from CKO (myoblast/CKO) mice were used to extend the findings to in vitro effects on myoblast differentiation and fusion. Quantitative real-time PCR, western blot and immunofluorescence approaches were used to analyse Slo1 expression during myoblast differentiation and muscle regeneration. To investigate the involvement of genes in the regulation of muscle dysfunction induced by Slo1 deletion, RNA-seq analysis was performed in primary myoblasts. Immunoprecipitation and mass spectrometry were used to identify the protein interacting with Slo1. A dual-luciferase reporter assay was used to identify whether Slo1 deletion affects NFAT activity. RESULTS: We found that the body weight and size of CKO mice were not significantly different from those of Slo1flox/flox mice (called WT). Deficiency of Slo1 in muscles leads to reduced endurance (~30% reduction, P < 0.05) and strength (~30% reduction, P < 0.001). Although there was no difference in the general morphology of the muscles, electron microscopy revealed a considerable reduction in the content of mitochondria in the soleus muscle (~40% reduction, P < 0.01). We found that Slo1 was expressed mainly on the cell membrane and showed higher expression in slow-twitch fibres. Slo1 protein expression is progressively reduced during muscle postnatal development and regeneration after injury, and the expression is strongly reduced during myoblast differentiation. Slo1 deletion impaired myoblast differentiation and slow-twitch fibre formation. Mechanistically, RNA-seq analysis showed that Slo1 influences the expression of genes related to myogenic differentiation and slow-twitch fibre formation. Slo1 interacts with FAK to influence myogenic differentiation, and Slo1 deletion diminishes NFAT activity. CONCLUSIONS: Our data reveal that Slo1 deficiency impaired skeletal muscle regeneration and slow-twitch fibre formation.

Corrigendum: Wenshen-Jianpi prescription, a Chinese herbal medicine, improves visceral hypersensitivity in a rat model of IBS-D by regulating the MEK/ERK signal pathway.

[This corrects the article DOI: 10.3389/fphar.2022.955421.].

Wenshen-Jianpi prescription, a Chinese herbal medicine, improves visceral hypersensitivity in a rat model of IBS-D by regulating the MEK/ERK signal pathway.

The goal of the study was to analyze whether WJP can alleviate visceral hypersensitivity in IBS-D model rats. In this study, 36 Sprague-Dawley (SD) rats aged 4 weeks old were randomly divided into two groups: the model group (n = 27) and the control group (n = 9). The rat model of IBS-D was established by modified compound methods for 4 weeks. After the modification, IBS-D rats were randomly divided into three groups, namely, the IBS-D model group (n = 9), the positive drug group (n = 9), and the WJP group (n = 9), with different interventions, respectively. The control group was fed and allowed to drink water routinely. The Bristol stool scale scores were used to assess the severity of diarrhea. Abdominal withdrawal reflex (AWR) scores were used to assess visceral sensitivity. Expression of TNF-α was measured, and histopathological examinations were performed to assess colon inflammation in IBS-D model rats. Key factors of the MEK/ERK signal pathway in the tissue of the colon and hippocampus were measured to analyze the mechanism of WJP. Compared with the control group, the Bristol stool scale scores in the model group were significantly increased (p < 0.0001). The scores of the WJP group were significantly decreased compared with the model group (p = 0.0001). Compared with the control group, AWR scores in the model group at each pressure level were significantly increased (p = 0.0003, p < 0.0001, p = 0.0007, and p = 0.0009). AWR scores of the WJP group were significantly decreased compared with the model group (p = 0.0003, p = 0.0007, p = 0.0007, and p = 0.0009). Compared with the control group, the model group had significantly higher expression of TNF-α in the colon tissue (p < 0.0001). However, the WJP group had significantly lower level of TNF-α compared with the model group (p < 0.0001). Meanwhile, compared with the control group, the relative expression of the proteins of p-MEK1/2, p-ERK1, and p-ERK2 in the colon tissue was significantly increased in the model group (p < 0.0001). Compared with the model group, the relative expression of the proteins in the colon tissue were significantly decreased in the WJP group (p < 0.0001, p = 0.0019, and p = 0.0013). Compared with the control group, the relative expression of the proteins of p-MEK1/2, p-ERK1, and p-ERK2 in the hippocampus tissue were significantly increased in the model group (p < 0.0001). Compared with the model group, the relative expression of the proteins in the hippocampus tissue were significantly decreased in the WJP group (p = 0.0126, p = 0.0291, and p = 0.0145). The results indicated that WJP can alleviate visceral hypersensitivity in IBS-D model rats, possibly mediated by downregulating the expression of TNF-α, p-MEK1/2, p-ERK1, and p-ERK2 in the colon tissue. At the same time, WJP also affects downregulating the expression of p-MEK1/2, p-ERK1, and p-ERK2 in the hippocampus tissue.

Chinese Herbal Medicine for Functional Dyspepsia With Psychological Disorders: A Systematic Review and Meta-Analysis.

Background and Aims: Functional dyspepsia (FD) is closely associated with gut-brain interaction disorder (DGBI), characterized by the interaction of gastrointestinal symptoms and central nervous system dysregulation. Chinese herbal medicine (CHM) has a good concurrent effect in the treatment of FD, especially for patients with concurrent psychological disorders. A meta-analysis was designed to evaluate the efficacy and safety of CHMs in the treatment of FD. Methods: The PubMed, Embase, Cochrane Library, Web of Science, Chinese Biological Medical Database (CBM), Wanfang Data, China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (VIP) were searched to collect randomized controlled trials of FD treated with CHM. The retrieval time limit is from the establishment of the database till 11 April 2022. Two researchers independently searched databases, screened documents, extracted data, and evaluated the risk of bias of included studies. RevMan 5.4 software was used for meta-analysis. Results: A total of 11 studies including 951 patients were included. The study was divided into two parts. The first part included 5 clinical trials, including 471 patients. The experimental group was treated only with CHM and the control group was only treated with placebo. The results of first part showed that the total effective rate of CHM in the treatment of FD was higher than that in the placebo group (84.5 vs. 49.4%) [relative risk (RR) = 1.76; 95% confidence interval (CI) (1.13, 2.75); P = 0.01]. In addition, CHM treatment could reduce the total symptom score [standardized mean difference (SMD) = -10.05; 95% CI (-13.50, -6.59); Z = 5.70; P < 0.0001] and depression score [SMD = -7.68; 95% CI (-14.43, -0.94); Z = 2.23; P = 0.03]. The second part included 6 clinical trials, including 480 patients. The experimental group was only treated with CHM and the control group was treated with prokinetic agents combined with flupentixol melitracen (deanxit). The results of second part showed that the total effective rate of CHM in the treatment of FD was higher than that of the control group (92.6 vs. 78.8%) [RR = 1.17; 95% CI (1.09, 1.26), P < 0.0001]. In addition, CHM treatment could reduce HAMA score [mean difference (MD) = -3.19; 95% CI (-3.79, -2.59); Z = 10.40; P < 0.00001], HAMD score [MD = -4.32; 95% CI (-6.04, -2.61); Z = 4.94; P < 0.00001], and gastric emptying rate [MD = 12.62; 95% CI (5.84, 19.40); Z = 3.65; P = 0.0003]. The results of the two parts of the meta-analysis showed no serious adverse reactions, and there was no significant difference in the adverse reactions between the experimental group and the control group [MD = 1.14; 95% CI (0.53, 2.42); Z = 0.33; P = 0.74]; [MD = 0.14; 95% CI (0.01, 2.67); Z = 1.30; P = 0.19]. Conclusion: The current evidence shows that CHM treatment has great potential and safety in alleviating the symptoms of FD and improving the psychological disorders of anxiety and depression in patients with FD. Limited by the quantity and quality of the included studies and other biases, the above conclusions need more high-quality studies to be verified. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier [CRD42022311129].

Resveratrol Synergistically Promotes BMP9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells.

Background: Mesenchymal stem cells (MSCs) differentiate into osteocytes, adipocytes, and chondrocytes. Resveratrol and bone morphogenetic protein 9 (BMP9) are known osteogenic induction factors of MSCs, but the effect of both resveratrol and BMP9 on osteogenesis is unknown. Herein, we explored whether resveratrol cooperates with BMP9 to improve osteogenic induction. Methods: The osteogenic induction of resveratrol and BMP9 on C3H10T1/2 cells was evaluated by detecting the staining and activity of the early osteogenic marker alkaline phosphatase (ALP). In addition, the late osteogenic effect was measured by the mRNA and protein levels of osteogenic markers, such as osteopontin (OPN) and osteocalcin (OCN). To assess the bone formation function of resveratrol plus BMP9 in vivo, we transplanted BMP9-infected C3H10T1/2 cells into nude mice followed by intragastric injection of resveratrol. Western blot (WB) analysis was utilized to elucidate the mechanism of resveratrol plus BMP9. Results: Resveratrol not only enhanced osteogenic induction alone but also improved BMP9-induced ALP at 3, 5, and 7 d postinduction. Both the early osteogenic markers (ALP, Runx2, and SP7) and the late osteogenic markers (OPN and OCN) were significantly increased when resveratrol was combined with BMP9. The fetal limb explant culture further verified these results. The in vivo bone formation experiment, which involved transplanting BMP9-overexpressing C3H10T1/2 cells into nude mice, also confirmed that resveratrol synergistically enhanced the BMP9-induced bone formation function. Resveratrol phosphorylated adenosine monophosphate- (AMP-) activated protein kinase (AMPK) and stimulated autophagy, but these effects were abolished by inhibiting AMPK and Beclin1 using an inhibitor or siRNA. Conclusions: Resveratrol combined with BMP9 significantly improves the osteogenic induction of C3H10T1/2 cells by activating AMPK and autophagy.

Efficacy and Safety of Chinese Herbal Medicine Xiao Yao San in Functional Gastrointestinal Disorders: A meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials.

Background and Aims: Functional gastrointestinal disorders are now named disorders of gut-brain interaction (DGBI) according to the Rome IV criteria, characterized by the interaction of gastrointestinal symptoms and dysregulation of central nervous systems. Xiao-Yao-San (XYS) is effective in the treatment of gastrointestinal symptoms in China, especially in patients with concurrent mood disorders. A meta-analysis was designed to evaluate the efficacy and safety of Xiao-Yao-San for FGIDs. Methods: We searched randomized controlled trials in seven databases from their inception till November 22, 2021. Pooled analysis included therapeutic efficacy, symptom score, Self-Rating Anxiety Scale (SAS) score, Self-Rating Depression Scale (SDS) score, and the recurrence rate. Conventional meta-analysis with random-effects model or fixed-effects model and trial sequential analysis (TSA) were performed. Results: A total of 48 RCTs were eligible for inclusion (n = 4,403). Meta-analysis results showed that XYS could improve the effective rate of FGIDs compared with western drugs [RR = 1.23; (95%CI, 1.19-1.27); p < 0.00001], and XYS combined with western medicine could also improve the effective rate [RR = 1.26; (95%CI, 1.21-1.33); p < 0.00001]. In addition, XYS could reduce the symptom score [SMD = -1.07; (95%CI -1.42, -0.72); Z = 6.03; p < 0.00001], SAS score [MD = -6.24; (95%CI -7.48, -4.99); Z = 9.81; p < 0.00001] and SDS score [MD = -6.70; (95%CI -8.18, -5.21); Z = 8.83; p < 0.00001] of FGIDs patients, and reduce the recurrence rate [MD = -6.70; (95%CI -8.18, -5.21); Z = 8.83; p < 0.00001]. XYS was safe in most cases and no serious adverse events were observed in any of the included trials. TAS showed adequate "information size" for the primary outcome, and further confirmed the efficacy of XYS in the treatment of FGIDs. Conclusion: XYS could improve symptoms and reduce recurrence rates in FGIDs patients, and XYS may be a potential candidate for the treatment of FGIDs. However, due to the limited quality of current studies, more long-term, randomized, double-blinded clinical trials are needed in future studies. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=284308, identifier CRD42021284308.

Triiodothyronine Potentiates BMP9-Induced Osteogenesis in Mesenchymal Stem Cells Through the Activation of AMPK/p38 Signaling.

Thyroid hormone (TH), triiodothyronine (T3), and thyroxine (T4), which are released from the thyroid, control many cellular processes in various cell types. It is worth noting that TH plays a complex role in skeletal metabolic balance, and few studies have investigated whether TH exerts any effects on osteogenesis in bone mesenchymal stem cells (MSCs). We explored the effects of T3 on bone morphogenetic protein 9 (BMP9)-induced osteogenesis, which process is considered the most important in the osteogenic differentiation of C3H10T1/2 cells. In vitro osteogenesis was analyzed by alkaline phosphatase (ALP) activity and staining, bone mineralisation, and osteocalcin and osteopontin expression. Fetal limb explant cultures and ectopic MSC implantation further confirmed the role of T3. Finally, we examined the effect of AMPK/p38 signaling on the osteoblastic differentiation. T3 synergizes with BMP9 to enhance osteogenic marker expression induced by BMP9. Furthermore, T3 promotes BMP9-induced bone formation by fetal limb explant cultures and ectopic MSC implantation. Co-treatment with BMP9 and T3 can promote AMPK and p38 phosphorylation, and pretreatment with the AMPK inhibitor compound C and siRNA can abolish phosphorylation of p38 and BMP9+T3-induced ALP activity. Our results suggest that BMP9 and T3 promote osteogenic differentiation at least partially via the activation of the AMPK/p38 signaling pathway.

EDTA-Modified 17ß-Estradiol-Laden Upconversion Nanocomposite for Bone-Targeted Hormone Replacement Therapy for Osteoporosis.

Hormone therapy (HT) is one of the most effective treatments for osteoporosis. However, the nonselective accumulation of hormone in organs such as breast, heart and uterus other than bones causes serious side effects, which impedes the application of HT. Hence, it is critically important to develop a HT strategy with reduced non-specific enrichment of hormone drugs in non-target tissues and enhanced bone-targeting ability. Methods: Herein, a 17ß-estradiol (E2)-laden mesoporous silica-coated upconversion nanoparticle with a surface modification of ethylenediaminetetraacetic acid (EDTA) (NaLuF4:Yb,Tm@NaLuF4@mSiO2-EDTA-E2, E2-csUCNP@MSN-EDTA) is developed for bone-targeted osteoporosis hormone therapy. EDTA was attached onto the surface of E2 upconversion nanocomposite to enhance its affinity and efficiency targeting bone tissue and cells to optimize hormone replacement therapy for osteoporosis. We characterized the size, cytotoxicity, loading and release efficiency, in situ and ex vivo imaging. Further, in vitro and in vivo osteogenic ability was tested using preosteoblast and ovariectomy mouse model of osteoporosis. Results: The upconversion core of E2-csUCNP@MSN-EDTA nanoparticle serves as an excellent imaging agent for tracking the loaded hormone drug in vivo. The mesoporous silica layer has a high loading efficiency for E2 and provides a relatively long-lasting drug release within 50 h. EDTA anchored on the silica layer endows the nanocomposite with a bone targeting property. The nanocomposite effectively reverses estrogen deficiency-induced osteoporosis and reduces the damage of hormone to the uterus. The bone mineral density in the nanocomposite treatment group is nearly twice that of the ovariectomized (OVX) group. Compared with the E2 group, the uterine weight and luminal epithelial height were significantly lower in the nanocomposite treatment group. Conclusion: This work demonstrated that E2-csUCNP@MSN-EDTA alleviates the side effect of hormone therapy while maintaining its therapeutic efficacy, which has great potential for developing the next generation of methods for osteoporosis treatment.

The p53/miR-145a Axis Promotes Cellular Senescence and Inhibits Osteogenic Differentiation by Targeting Cbfb in Mesenchymal Stem Cells.

The osteogenic differentiation capacity of senescent bone marrow mesenchymal stem cells (MSCs) is reduced. p53 not only regulates cellular senescence but also functions as a negative regulator in bone formation. However, the role of p53 in MSCs senescence and differentiation has not been extensively explored. In the present study, we investigated the molecular mechanism of p53 in MSCs senescence and osteogenic differentiation. We found that p53 was upregulated during cellular senescence and osteogenic differentiation of MSCs respectively induced by H2O2 and BMP9. Similarly, the expression of p53-induced miR-145a was increased significantly. Furthermore, Overexpression of miR-145a in MSCs promoted cellular senescence and inhibited osteogenic differentiation. Then, we identified that p53-induced miR-145a inhibited osteogenic differentiation by targeting core binding factor beta (Cbfb), and the restoration of Cbfb expression rescued the inhibitory effects of miRNA-145a. In summary, our results indicate that p53/miR-145a axis exert its functions both in promoting senescence and inhibiting osteogenesis of MSCs, and the novel p53/miR-145a/Cbfb axis in osteogenic differentiation of MSCs may represent new targets in the treatment of osteoporosis.

Melatonin promotes the BMP9-induced osteogenic differentiation of mesenchymal stem cells by activating the AMPK/ß-catenin signalling pathway.

BACKGROUND: Mesenchymal stem cells (MSCs) play a crucial role in maintaining the dynamic balance of bone metabolism. Melatonin may have a regulatory effect on bone metabolism by regulating the lineage commitment and differentiation signalling pathways of MSCs. Among the BMP families, the osteogenesis of BMP9 is considered to be one of the strongest in MSCs. Here, we explored whether melatonin and BMP9 act synergistically on MSC osteogenic differentiation. METHODS: The C3H10T1/2 osteogenic differentiation function induced by melatonin synergizes with BMP9, as detected by the expression of osteogenic markers at different periods. The result was further confirmed by foetal limb explant culture and in vivo stem cell implantation experiments. The effects of the AMPK/ß-catenin pathway on the osteogenic differentiation of C3H10T1/2 cells were evaluated by Western blotting. RESULTS: Melatonin combined with BMP9 significantly enhanced the expression of osteogenic markers at different periods in C3H10T1/2 cells, effectively enhancing BMP9-induced bone formation in cultured foetal explants and ectopic bone formation in vivo in stem cell transplantation experiments. Melatonin increases the expression of BMP9 in C3H10T1/2 cells and induces Smad1/5/8 translocation from the cytoplasm to the nucleus. In addition, melatonin and BMP9 synergistically promote AMPK and ß-catenin phosphorylation, which can be largely eliminated by AMPK siRNA pretreatment. CONCLUSIONS: Melatonin and BMP9 in C3H10T1/2 cells synergistically promote osteogenic differentiation at least in part by activating the AMPK/ß-catenin signalling pathway.

Jieduan-Niwan Formula Reduces Liver Apoptosis in a Rat Model of Acute-on-Chronic Liver Failure by Regulating the E2F1-Mediated Intrinsic Apoptosis Pathway.

Acute-on-chronic liver failure (ACLF) is a serious and complicated disease that threatens human health because its pathogenesis is unclear, and the outcome of the current therapies has been less than satisfactory. A national famous doctor of traditional Chinese medicine, Qian Ying, created the Jieduan-Niwan Formula (JDNW), based on his long-term clinical experience. However, despite the good clinical outcome, the biological mechanism by which it works is unknown. In the current study, we established an ACLF rat model by administering human serum albumin (HSA) combined with D-galactosamine (D-GalN) and lipopolysaccharide (LPS) to explore the potential mechanism of JDNW in treating ACLF. The rats were treated with JDNW by administration of the model substances and sacrificed after 4, 8, and 12 h. Then we divided the rats into normal group, model at 4 h, model at 8 h, model at 12 h, JDNW at 4 h, JDNW at 8 h, and JDNW at 12 h. Biochemical and histopathological examinations were performed to compare the rats in different groups. Compared with the ACLF model group, expression levels of alanine transaminase, aspartate aminotransferase, total bilirubin, and TNF-α and IL-6 proteins were reduced in the JDNW group at the corresponding time points, the survival rates of rats were increased, and the pathological condition of the liver was improved. In addition, JDNW treatment improved the ultrastructure of hepatocytes and mitochondria and decreased the hepatocyte apoptosis index. E2F1, P53, P73, Apaf-1, p14ARF, caspase-3, caspase-6, and caspase-7 levels in the JDNW group were distinctly lower than those in the untreated rats. Moreover, Bcl-2 and Mcl-1 levels increased. Thus, JDNW decreases ACLF-induced mortality in rats by modulating the E2F1-mediated intrinsic apoptotic pathway.