Unique metabolomics characteristics for distinguishing cirrhosis related to different liver diseases: A systematic review and meta-analysis.

BACKGROUND AND AIM: Clinical evidence for early identification and diagnosis of liver cirrhosis (LC) caused by different types of liver disease is limited. We investigated this topic through a meta-analysis of quantitative metabolomics. METHODS: Four databases were searched until October 31, 2022 for studies comparing metabolite levels between patients with different types of liver disease and control individuals. A random-effects model was applied for the meta-analysis. RESULTS: This study included 55 studies with 8266 clinical participants, covering 348 metabolites. In LC related to drug-induced liver injury (DILI), hepatitis B virus (HBV) infection, and non-alcoholic fatty liver disease (NAFLD), the primary bile acid biosynthesis (taurocholic acid: SMD, 1.08[0.81, 1.35]; P < 0.00001; glycocholic acid: SMD, 1.35[1.07, 1.62]; P < 0.00001; taurochenodeoxycholic acid: SMD, 1.36[0.94, 1.78]; P < 0.00001; glycochenodeoxycholic acid: SMD, 1.49[0.93, 2.06]; P < 0.00001), proline and arginine (l-proline: SMD, 1.06[0.53, 1.58]; P < 0.0001; hydroxyproline: SMD, 0.81[0.30, 1.33]; P = 0.002), and fatty acid biosynthesis (palmitic acid: SMD, 0.44[0.21, 0.67]; P = 0.0002; oleic acid: SMD, 0.46[0.19, 0.73]; P = 0.0008; stearic acid: SMD, 0.37[0.07, 0.68]; P = 0.02) metabolic pathways were significantly altered. CONCLUSION: We identified key biomarkers and metabolic characteristics for distinguishing and identifying LC related to different types of liver disease, providing a new perspective for early diagnosis, disease monitoring, and precise treatment.

Babaodan inhibits cell proliferation and metastasis and enhances anti-tumor effects of camrelizumab by inhibiting M2 phenotype macrophages in hepatocellular carcinoma.

ETHNOPHARMACOLOGICAL RELEVANCE: Babaodan (BBD) is a unique Chinese medication utilized in traditional Chinese medicine. It can eliminate toxins, induce diuresis, and eliminate yellowish hue. In addition to treating acute and chronic viral hepatitis, cholecystitis, cholangitis, and urinary tract infections, BBD has garnered popularity as a substitution treatment for several malignant cancers, particularly hepatocellular carcinoma (HCC). AIM OF THE STUDY: To elucidate the efficacy and mechanism of BBD alone and combined with camrelizumab (CLM) for treating HCC. METHODS: We investigated the effects of BBD on the HCC tumor microenvironment in vivo. Furthermore, we evaluated its effects on tumor growth and metastasis induced by M2 macrophages in vitro. RESULTS: In a mouse model of orthotopic HCC, BBD decreased tumor growth. Furthermore, it increased the M1/M2 macrophage ratio and CD8+ T-cell abundance in mice. In addition, BBD reversed HCC cell proliferation and metastasis induced by M2 macrophages, increased the anti-HCC effect of low-dose CLM, and attenuated organ damage induced by high-dose CLM. Lastly, BBD enhanced the efficacy of CLM via the PI3K/AKT/mTOR signaling pathway. CONCLUSION: BBD increases the antitumor effect of CLM by modulating the tumor immune microenvironment and attenuating its the toxic side effects of CLM.

The role of NCAPH in cancer treatment.

Many solid tumors frequently overexpress Non-SMC Condensin I Complex Subunit H (NCAPH), and new studies suggest that NCAPH may be a target gene for clinical cancer therapy. Numerous investigations have shown that a variety of transcription factors, including as MYBL2, FOXP3, GATA3, and OTC1, can stimulate the transcription of NCAPH. Additionally, NCAPH stimulates many oncogenic signaling pathways, such as ß-Catenin/PD-L1, PI3K/AKT/SGK3, MEK/ERK, AURKB/AKT/mTOR, PI3K/PDK1/AKT, and Chk1/Chk2. Tumor immune microenvironment modification and tumor growth, apoptosis, metastasis, stemness, and treatment resistance all depend on these signals. NCAPH has the ability to form complexes with other proteins that are involved in glycolysis, DNA damage repair, and chromatin remodeling. This review indicates that NCAPH expression in most malignant tumors is associated with poor prognosis and low recurrence-free survival.

Construction of a physiologically based pharmacokinetic model of paclobutrazol and exposure estimation in the human body.

Paclobutrazol (PBZ) is a plant growth regulator that can delay plant growth and improve plant resistance and yield. Although it has been widely used in the growth of medicinal plants, human beings may take it by taking traditional Chinese medicine. There are no published studies on PBZ exposure in humans or standardized limits for PBZ in medicinal plants. We measured the solubility, oil-water partition coefficient (logP), and pharmacokinetics of PBZ in rats and established a physiologically based pharmacokinetic (PBPK) model of PBZ in rats. This was followed by extrapolation to healthy Chinese adult males as a theoretical foundation for future risk assessment of PBZ. The results showed that PBZ had low solubility and high fat solubility. Pharmacokinetic experiments showed that PBZ was absorbed rapidly but eliminated slowly in rats. On this basis, the rat PBPK model was successfully constructed and extrapolated to healthy Chinese adult males to predict the plasma concentration-time curve and exposure of PBZ in humans. The construction of the PBPK model of PBZ in this study facilitates the determination of the standard formulation limits and risk assessment of PBZ residues in medicinal plants.

PEG-PVP-Assisted Hydrothermal Synthesis and Electrochemical Performance of N-Doped MoS2/C Composites as Anode Material for Lithium-Ion Batteries.

Molybdenum disulfide shows promise as an anode material for lithium-ion batteries. However, its commercial potential has been constrained due to the poor conductivity and significant volume expansion during the charge/discharge cycles. To address these issues, in this study, N-doped MoS2/C composites (NMC) were prepared via an enhanced hydrothermal method, using ammonium molybdate and thiourea as molybdenum and sulfur sources, respectively. Polyethylene glycol 400 (PEG400) and polyvinylpyrrolidone (PVP) were added in the hydrothermal procedure as soft template surfactants and nitrogen/carbon sources. The crystal structure, morphology, elemental composition, and surface valence state of the N-doped MoS2/C composites were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), high-resolution transmission electron microscopy (HRTEM), and X-ray photoelectron spectroscopy (XPS), respectively. The results indicate that the NMC prepared by this method are spherical particles with a nanoflower-like structure composed of MoS2 flakes, having an average particle size of about 500 nm. XPS analysis shows the existence of C and N elements in the samples as C-N, C-C, and pyrrolic N. As anodes for LIBs, the NMC without annealing deliver an initial discharge capacity of 548.2 mAh·g-1 at a current density of 500 mA·g-1. However, this capacity decays in the following cycles with a discharge capacity of 66.4 mAh·g-1 and a capacity retention rate of only 12% after 50 cycles. In contrast, the electrochemical properties of the counterparts are enhanced after annealing, which exhibits an initial discharge capacity of 575.9 mAh·g-1 and an ultimate discharge capacity of 669.2 mAh·g-1 after 70 cycles. The capacity retention rate decreases initially but later increases and elevated afterward to reach 116% at the 70th cycle, indicating an improvement in charge-discharge performance. The specimens after annealing have a smaller impedance, which indicates better charge transport and lithium-ion diffusion performance.

Analysis of chemical components of Jianwei Xiaoshi Tablets based on UPLC-Q-Orbitrap-MS technology.

As a compound preparation of traditional Chinese medicine, Jianwei Xiaoshi Tablets (JXT) is made from five Chinese herbs: Taizishen (Pseudostellariae Radix), Chenpi (Citri Reticulatae Pericarpium), Shanyao (Dioscoreae Rhizoma), Maiya (Hordei Fructus Germinatus) and Shanzha (Crataegi Fructus). It is mainly used to treat dyspepsia. However, the chemical composition of JXT is complex and unclear. In this study, ultra performance liquid chromatography-quadrupole-orbitrap-mass spectrometry and data post-processing technologies were used to analyse the samples of JXT. Firstly, the mass spectrometric information of the main components of five traditional Chinese herbs in JXT was summarised and a compound database was established. Then, the mass spectrometric data detected by the prepared samples was compared with the database. Finally, 93 chemical components were successfully identified, including 6 amino acids, 34 flavonoids, 18 alkaloids, 15 organic acids, 9 cyclic peptides and 11 other components, and the rapid classification and identification of chemical components of JXT were realised.

Early Warning of Ischemic Stroke Based on Atherosclerosis Index Combined With Serum Markers.

CONTEXT: Ischemic stroke (IS) is a serious public health problem worldwide, threatening human life and health. Atherosclerosis is the cause of stroke. At present, there are few selective indexes that can be used to evaluate atherosclerosis in the clinic; providers rely mainly on the atherosclerotic index (AI). Disturbance of lipid metabolism is considered to be a key event leading to IS. OBJECTIVE: The purpose of this study was to discover potential biomarkers in the serum of atherosclerosis-induced IS, combined with the AI to provide early warning for the diagnosis of IS. METHODS: In this study, we used nontargeted metabolomics based on ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) to measure the changes in serum metabolites in a group of patients with IS. To verify the reproducibility of candidate biomarkers in the population, we expanded the sample size. RESULTS: Five metabolites were identified, including sphingomyelin (18:0/14:0), 1-Methylpyrrolinium, PC (18:0/18:0), LysoPC (18:0/0:0), and PC (18: 2/18:2). The combination of these 5 metabolic markers has good diagnostic and predictive ability, and the change level of these metabolites is significantly related to IS. Our results also indicate that changes in glycerophospholipid metabolism may indicate an early risk of IS development. CONCLUSION: These findings may contribute to the development of new diagnostic methods of potential biomarkers in serum combined with the AI, thereby providing early warning for the diagnosis of atherosclerosis-induced IS, and may provide a new insights for pathogenesis in IS.

FPGA-Based Implementation of Multidimensional Reconciliation Encoding in Quantum Key Distribution.

We propose a multidimensional reconciliation encoding algorithm based on a field-programmable gate array (FPGA) with variable data throughput that enables quantum key distribution (QKD) systems to be adapted to different throughput requirements. Using the circulatory structure, data flow in the most complex pipeline operation in the same time interval, which enables the structural multiplexing of the algorithm. We handle the calculation and storage of eight-dimensional matrices cleverly to conserve resources and increase data processing speed. In order to obtain the syndrome more efficiently, we designed a simplified algorithm according to the characteristics of the FPGA and parity-check matrix, which omits the unnecessary operation of matrix multiplication. The simplified algorithm could adapt to different rates. We validated the feasibility and high speed of the algorithm by implementing the multidimensional reconciliation encoding algorithm on a Xilinx Virtex-7 FPGA. Our simulation results show that the maximum throughput could reach 4.88 M symbols/s.

Cyclin-dependent kinase 1 as a potential target for lycorine against hepatocellular carcinoma.

The pathological changes and possible underlying molecular mechanisms of hepatocellular carcinoma (HCC) are currently unclear. Effective treatment of this pathological state remains a challenge. The purpose of this study is to obtain some key genes with diagnostic and prognostic meaning and to identify potential therapeutic agents for HCC treatment. Here, CDK1, CCNB1 and CCNB2 were found to be highly expressed in HCC patients and accompanied by poor prognosis, and knockdown of them by siRNA drastically induced autophagy and senescence in hepatoma cells. Simultaneously, the anti-HCC effect of lycorine was comparable to that of interfering with these three genes, and lycorine significantly promoted the decrease both in protein and mRNA expression of CDK1. Molecular validation mechanistically demonstrated that lycorine might attenuate the degradation rate of CDK1 via interaction with it, which had been confirmed by cellular thermal shift assay and drug affinity responsive targets stability assay. Taken together, these findings suggested that CDK1, CCNB1 and CCNB2 could be regarded as potential diagnostic and prognostic biomarkers for HCC, and CDK1 might serve as a promising therapeutic target for lycorine against HCC.

Application of lipidomics strategy to explore aging-related biomarkers and potential anti-aging mechanisms of ginseng.

Aging often leads to an increase risk of age-related diseases, and the development of anti-aging drugs have become the trend and focus of the current scientific research. In this experiment, serum samples from healthy people of different ages were analyzed based on clinical lipidomics, and a total of 10 potential biomarkers in middle-aged and youth group, 20 biomarkers in the youth and the elderly group were obtained. Furthermore, dhSph and dhCer involved above may affect the aging process through sphingolipid metabolic pathway. As the first and rate-limiting step of catalyzing de novo sphingolipid pathway, SPT may play a key role in human anti-aging, which is revealed by lipidomics liposome tracer analysis. The potential active components in ginseng on SPT was further verified by molecular docking virtual screening and atomic force microscope. Four ingredients of ginseng may reduce the levels of metabolites dhSph and dhCer by inhibiting the activity of SPT, and play an anti-aging effect by affecting the sphingolipid metabolism pathway.A clinical trials registration number: ChiCTR1900026836.

Determination of Alkaloids and Flavonoids in Sophora flavescens by UHPLC-Q-TOF/MS.

This study is based on UHPLC-Q-TOF/MS and fragment ions to achieve classification and identification of alkaloids and flavonoids in Sophora flavescens. By reviewing the available and relevant literature, the mass fragmentation rules of alkaloids and flavonoids were summarized. 0.1% formic acid water (A) and acetonitrile (B) were used as mobile phases. 37 chemical constituents were identified, including 13 alkaloids and 24 flavonoids. This research method offers a complete strategy based on the fragmentation information of characteristic fragment ions and neutral loss obtained by MS/MS to characterize the chemical composition of Sophora flavescens.

Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology.

BACKGROUND: Rhubarb, as a traditional Chinese medicine, is the preferred drug for the treatment of stagnation and constipation in clinical practice. It has been reported that rhubarb possesses hepatotoxicity, but its mechanism in vivo is still unclear. METHODS: In this study, the chemical components in rhubarb were identified based on UPLC-Q-TOF/MS combined with data postprocessing technology. The metabolic biomarkers obtained through metabolomics technology were related to rhubarb-induced hepatotoxicity. Furthermore, the potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology involving the above components and metabolites. Meanwhile, GO gene enrichment analysis and KEGG pathway analysis were performed on the common targets. RESULTS: Twenty-eight components in rhubarb were identified based on UPLC-Q-TOF/MS, and 242 targets related to rhubarb ingredients were predicted. Nine metabolic biomarkers obtained through metabolomics technology were closely related to rhubarb-induced hepatotoxicity, and 282 targets of metabolites were predicted. Among them, the levels of 4 metabolites, namely dynorphin B (10-13), cervonoyl ethanolamide, lysoPE (18:2), and 3-hydroxyphenyl 2-hydroxybenzoate, significantly increased, while the levels of 5 metabolites, namely dopamine, biopterin, choline, coenzyme Q9 and P1, P4-bis (5'-uridyl) tetraphosphate significantly decreased. In addition, 166 potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology. The KEGG pathway analysis was performed on the common targets to obtain 46 associated signaling pathways. CONCLUSION: These data suggested that rhubarb may cause liver toxicity due to its action on dopamine D1 receptor (DRD1), dopamine D2 receptor (DRD2), phosphodiesterase 4B (PDE4B), vanilloid receptor (TRPV1); transient receptor potential cation channel subfamily M member 8 (TRPM8), prostanoid EP2 receptor (PTGER2), acetylcholinesterase (ACHE), muscarinic acetylcholine receptor M3 (CHRM3) through the cAMP signaling pathway, cholinergic synapses, and inflammatory mediators to regulate TRP channels. Metabolomics technology and network pharmacology were integrated to explore rhubarb hepatotoxicity to promote the reasonable clinical application of rhubarb.

Development and validation of a nomogram to predict the risk of breast cancer-related lymphedema among Chinese breast cancer survivors.

PURPOSE: Breast cancer-related lymphedema (BCRL) is a major long-term complication for post-surgery breast cancer survivors. Although several risk factors have been identified, lifestyle characteristics have been neglected in previous studies. The aim of this study was to develop and validate a nomogram for estimating this population's risk of developing lymphedema, taking into consideration their demographic, clinical, and personal lifestyle behaviors. METHODS: In a cross-sectional study, we collected data from 775 post-operative breast cancer survivors who had attended a follow-up session in the recent 10 years (primary cohort). Lymphedema was assessed using the Norman telephone questionnaire, self-reported by patients. Multiple logistic regression was used to identify risk factors for lymphedema, including demographic, clinical, and lifestyle-related factors. A nomogram was constructed based on those factors and was validated using a separate group of 314 breast cancer patients (validation cohort). RESULTS: The factors independently associated with lymphedema were higher body mass index (BMI), modified radical mastectomy (MRM), postsurgical infection, chemotherapy, radiotherapy, exercise of the affected arm, and the active participation in physical activity (P<0.05). The area under the curve (AUC) values of the primary and the validation cohorts were 0.721 (95% confidence interval: 0.685-0.756) and 0.702 (95% confidence interval: 0.646-0.759), respectively. CONCLUSIONS: BCRL risk factors include MRM, radiotherapy, chemotherapy, and higher BMI, while the active physical activity behavior of patients appears to be a factor against lymphedema. The nomogram incorporating the patients' clinical and lifestyle factors might be useful for predicting lymphedema in breast cancer survivors.

Efficient FPGA implementation of high-speed true random number generator.

High-speed true random number generator is a building block in the modern information security system. We propose and demonstrate an efficient high-speed true random number generator based on multiple parallel self-timed rings (STRs). To improve the security, we evaluate the randomness of the entropy source by min-entropy and exploit the information-theoretically provable Toeplitz-hashing extractor. To minimize the consumption of hardware resources of a field programmable gate array at a predetermined high throughput and maximize the throughput with the limited hardware resources, we systematically derive and investigate the dependence of the data throughput and the total consumed resources of the random number generator on the system parameters. On this basis, we make a joint optimization for the degree of parallelism of the STRs and the extraction efficiency of the extractor. A 10-Gbps true random number generator is implemented efficiently, so that the output random bits can pass all the National Institute of Standards and Technology (NIST) and Dieharder test suites.

Prevalence and predictors of breast cancer-related arm lymphedema over a 10-year period in postoperative breast cancer patients: A cross-sectional study.

PURPOSE: Breast cancer (BC) survivors have a lifelong risk of developing lymphedema. This study investigated the prevalence of BC-related arm lymphedema among Chinese BC survivors diagnosed in the last 10 years and examined the demographic and clinical variables as well as lifestyle factors associated with lymphedema status. METHODS: In this cross-sectional study, women with BC (N = 866) who had been diagnosed and followed up in the previous 10 years were recruited from the outpatient clinic of 4 general hospitals and one cancer association in China between August 2018 and October 2019. Lymphedema status was determined using the Norman telephone questionnaire as the patient-reported occurrence of hand/lower arm/upper arm swelling. Multiple logistic regression was used to identify risk factors for lymphedema. RESULTS: The median time from BC diagnosis was 4.0 years (interquartile range, 2.0-5.0 years). 81.4% of the patients had undergone mastectomy. The prevalence of arm lymphedema among BC survivors was 49.0%. Age ≥50 years, monthly income <3000 RMB, modified radical mastectomy, postsurgical wound infection, chemotherapy, and radiotherapy were associated with an increased risk of BC-related arm lymphedema, whereas exercise of the affected arm, engagement in active physical activity, and timely reporting of symptoms of infection to a physician decreased the risk (P < 0.05). CONCLUSIONS: Arm lymphedema is a common complication for postoperative BC survivors within 10 years. It is essential to identify patients at risk of lymphedema based on demographic, clinical, and lifestyle factors and implement interventions targeting modifiable lifestyle behaviors-eg, active physical activity during the postoperative period.

Cleavage rules of mass spectrometry fragments and rapid identification of chemical components of Radix Paeoniae Alba using UHPLC-Q-TOF-MS.

INTRODUCTION: Radix Paeoniae Alba (RPA) presents several pharmacological effects, including analgesia, liver protection, and toxicity reduction. RPA consists mostly of monoterpenes and their glycosides, tannins, flavonoids, and organic acids, with monoterpenes being the main active pharmaceutical ingredients. OBJECTIVE: To establish an effective method for rapid classification and identification of the main monoterpenes, flavonoids, and organic acids in RPA. METHODS: We used ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and data post-processing technology to rapidly classify and identify the monoterpenoids, flavonoids, and organic acids in RPA. We also summarised the diagnostic product ions and neutral losses of monoterpenoids, flavonoids, and organic acids in RPA reported in the literature. RESULTS: We identified 24 components, namely 18 monoterpenoids, one flavonoid, and five organic acids. CONCLUSION: In this study, we analysed the chemically active pharmaceutical ingredients and assessed the quality of RPA. In addition, we demonstrated that UHPLC-Q-TOF-MS can be used to qualitatively classify and identify the variety of chemical components of traditional Chinese medicines (TCMs) to a certain extent. Moreover, we confirmed that mass spectrometry can be used to identify the components of TCMs.

ASBT(SLC10A2): A promising target for treatment of diseases and drug discovery.

Bile acids has gradually become a new focus in various diseases, and ASBT as a transporter responsible for the reabsorption of ileal bile acids, is a key hinge associated to the bile acids-cholesterol balance and bile acids of enterohepatic circulation. The cumulative studies have also shown that ASBT is a promising target for treatment of liver, gallbladder, intestinal and metabolic diseases. This article briefly reviewed the process of bile acids enterohepatic circulation, as well as the regulations of ASBT expression, covering transcription factors, nuclear receptors and gut microbiota. In addition, the relationship between ASBT and various diseases were discussed in this paper. According to the structural classification of ASBT inhibitors, the research status of ASBT inhibitors and potential ASBT inhibitors of traditional Chinese medicine (such resveratrol, jatrorrhizine in Coptis chinensis) were summarized. This review provides a basis for the development of ASBT inhibitors and the treatment strategy of related diseases.

Cellular senescence and cancer: Focusing on traditional Chinese medicine and natural products.

Cancer is the principal cause of death and a dominant public health problem which seriously threatening human life. Among various ways to treat cancer, traditional Chinese medicine (TCM) and natural products have outstanding anti-cancer effects with their unique advantages of high efficiency and minimal side effects. Cell senescence is a physiological process of cell growth stagnation triggered by stress, which is an important line of defence against tumour development. In recent years, active ingredients of TCM and natural products, as an interesting research hotspot, can induce cell senescence to suppress the occurrence and development of tumours, by inhibiting telomerase activity, triggering DNA damage, inducing SASP, and activating or inactivating oncogenes. In this paper, the recent research progress on the main compounds derived from TCM and natural products that play anti-cancer roles by inducing cell senescence is systematically reviewed, aiming to provide a reference for the clinical treatment of pro-senescent cancer.

Effects of mindfulness-based cognitive therapy on breast cancer survivors with insomnia: A randomised controlled trial.

OBJECTIVE: We investigated the effects of mindfulness-based cognitive therapy on insomnia (MBCT-I) in breast cancer survivors. METHODS: In total, 136 participants were allocated randomly to a MBCT-I group or a waitlist control (WLC) group. Indicators of insomnia and mindfulness were evaluated using the Insomnia Severity Index, actigraphy and the Five Facet Mindfulness Questionnaire. Data were collected at baseline (T1), post-intervention (T2), 3-month follow-up (T3) and 6-month follow-up (T4) time points. RESULTS: Insomnia severity decreased significantly in the MBCT-I group, compared with the WLC group, at T2, T3 and T4 (all p < .001). We found that 59.6% of the MBCT-I group with moderate and severe insomnia improved to no insomnia and subclinical insomnia at T4 relative to T1, accounting for 7.9% and 55.3%, respectively. Compared with the WLC group, the MBCT-I group improved on actigraphy measures of sleep; they exhibited a pattern of decreased sleep onset latency and waking after sleep onset, as well as increased total sleep time and sleep efficiency. Mindfulness also increased more in the MBCT-I group than in the WLC group at T2, T3 and T4 (all p < .001). CONCLUSIONS: MBCT-I may be an efficacious non-pharmacologic intervention to improve sleep quality in breast cancer survivors.

HTBPI, an active phenanthroindolizidine alkaloid, inhibits liver tumorigenesis by targeting Akt.

Akt, a crucial protein involved in a variety of signaling pathways in cancer, acts as an important regulator of survival in hepatocellular carcinoma (HCC), and provides curative option for the related drugs development. We have found an active phenanthroindolizidine alkaloid, (13aR,14R)-9,11,12,13,13a,14-hexahydro-3,6,7-trimethoxydibenzo[f,h]pyrrolo[1,2-b]isoquinolin-14-ol (HTBPI), is a promising Akt inhibitor effective in the suppression of HCC cells proliferation through stimulating apoptotic and autophagic capability in vivo and in vitro. Treatment of HTBPI combined with a classical autophagy-lysosomal inhibitor (bafilomycin A1), could enhance stimulation effects of apoptosis on HCC cell lines. In addition, we confirmed HTBPI targeting Akt, occupied the kinase binding domain (Thr 308) of Akt to inactivate its function by CETSA and DARTS assay. In contrast, ectopic Akt-induced overexpression significantly abrogated inhibitory effects of HTBPI on cell viability and proliferation. Furthermore, high p-Akt (Thr 308) expression is collated with liver tumor formation and poor survival in HCC patients. In conclusions, HTBPI impeded HCC progress through regulation of apoptosis and autophagy machinery via interaction with p-Akt (Thr 308). This may provide potential molecular candidate by targeting Akt for the therapy of HCC patients.