Long-term hematopoietic transfer of the anti-cancer and lifespan-extending capabilities of a genetically engineered blood system by transplantation of bone marrow mononuclear cells.

A causal relationship exists among the aging process, organ decay and disfunction, and the occurrence of various diseases including cancer. A genetically engineered mouse model, termed Klf1K74R/K74R or Klf1(K74R), carrying mutation on the well-conserved sumoylation site of the hematopoietic transcription factor KLF1/EKLF has been generated that possesses extended lifespan and healthy characteristics, including cancer resistance. We show that the healthy longevity characteristics of the Klf1(K74R) mice, as exemplified by their higher anti-cancer capability, are likely gender-, age-, and genetic background-independent. Significantly, the anti-cancer capability, in particular that against melanoma as well as hepatocellular carcinoma, and lifespan-extending property of Klf1(K74R) mice, could be transferred to wild-type mice via transplantation of their bone marrow mononuclear cells at a young age of the latter. Furthermore, NK(K74R) cells carry higher in vitro cancer cell-killing ability than wild-type NK cells. Targeted/global gene expression profiling analysis has identified changes in the expression of specific proteins, including the immune checkpoint factors PDCD and CD274, and cellular pathways in the leukocytes of the Klf1(K74R) that are in the directions of anti-cancer and/or anti-aging. This study demonstrates the feasibility of developing a transferable hematopoietic/blood system for long-term anti-cancer and, potentially, for anti-aging.

Construction of a nomogram for predicting compensated cirrhosis with Wilson's disease based on non-invasive indicators.

BACKGROUND: Wilson's disease (WD) often leads to liver fibrosis and cirrhosis, and early diagnosis of WD cirrhosis is essential. Currently, there are few non-invasive prediction models for WD cirrhosis. The purpose of this study is to non-invasively predict the occurrence risk of compensated WD cirrhosis based on ultrasound imaging features and clinical characteristics. METHODS: A retrospective analysis of the clinical characteristics and ultrasound examination data of 102 WD patients from November 2018 to November 2020 was conducted. According to the staging system for WD liver involvement, the patients were divided into a cirrhosis group (n = 43) and a non-cirrhosis group (n = 59). Multivariable logistic regression analysis was used to identify independent influencing factors for WD cirrhosis. A nomogram for predicting WD cirrhosis was constructed using R analysis software, and validation of the model's discrimination, calibration, and clinical applicability was completed. Due to the low incidence of WD and the small sample size, bootstrap internal sampling with 500 iterations was adopted for validation to prevent overfitting of the model. RESULTS: Acoustic Radiation Force Impulse (ARFI), portal vein diameter (PVD), and serum albumin (ALB) are independent factors affecting WD cirrhosis. A nomogram for WD cirrhosis was constructed based on these factors. The area under the ROC curve (AUC) of the model's predictive ability is 0.927 (95% CI: 0.88-0.978). As demonstrated by 500 Bootstrap internal sampling validations, the model has high discrimination and calibration. Clinical decision curve analysis shows that the model has high clinical practical value. ROC curve analysis of the model's rationality indicates that the model's AUC is greater than the AUC of using ALB, ARFI, and PVD alone. CONCLUSION: The nomogram model constructed based on ARFI, PVD, and ALB can serve as a non-invasive tool to effectively predict the risk of developing WD cirrhosis.

Evaluation of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome: a prospective multicenter single-arm interventional study.

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS: In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

A pathway for chitin oxidation in marine bacteria.

Oxidative degradation of chitin, initiated by lytic polysaccharide monooxygenases (LPMOs), contributes to microbial bioconversion of crystalline chitin, the second most abundant biopolymer in nature. However, our knowledge of oxidative chitin utilization pathways, beyond LPMOs, is very limited. Here, we describe a complete pathway for oxidative chitin degradation and its regulation in a marine bacterium, Pseudoalteromonas prydzensis. The pathway starts with LPMO-mediated extracellular breakdown of chitin into C1-oxidized chitooligosaccharides, which carry a terminal 2-(acetylamino)-2-deoxy-D-gluconic acid (GlcNAc1A). Transmembrane transport of oxidized chitooligosaccharides is followed by their hydrolysis in the periplasm, releasing GlcNAc1A, which is catabolized in the cytoplasm. This pathway differs from the known hydrolytic chitin utilization pathway in enzymes, transporters and regulators. In particular, GlcNAc1A is converted to 2-keto-3-deoxygluconate 6-phosphate, acetate and NH3 via a series of reactions resembling the degradation of D-amino acids rather than other monosaccharides. Furthermore, genomic and metagenomic analyses suggest that the chitin oxidative utilization pathway may be prevalent in marine Gammaproteobacteria.

A Novel Gelatinase from Marine Flocculibacter collagenilyticus SM1988: Characterization and Potential Application in Collagen Oligopeptide-Rich Hydrolysate Preparation.

Although the S8 family in the MEROPS database contains many peptidases, only a few S8 peptidases have been applied in the preparation of bioactive oligopeptides. Bovine bone collagen is a good source for preparing collagen oligopeptides, but has been so far rarely applied in collagen peptide preparation. Here, we characterized a novel S8 gelatinase, Aa2_1884, from marine bacterium Flocculibacter collagenilyticus SM1988T, and evaluated its potential application in the preparation of collagen oligopeptides from bovine bone collagen. Aa2_1884 is a multimodular S8 peptidase with a distinct domain architecture from other reported peptidases. The recombinant Aa2_1884 over-expressed in Escherichia coli showed high activity toward gelatin and denatured collagens, but no activity toward natural collagens, indicating that Aa2_1884 is a gelatinase. To evaluate the potential of Aa2_1884 in the preparation of collagen oligopeptides from bovine bone collagen, three enzymatic hydrolysis parameters, hydrolysis temperature, hydrolysis time and enzyme-substrate ratio (E/S), were optimized by single factor experiments, and the optimal hydrolysis conditions were determined to be reaction at 60 ℃ for 3 h with an E/S of 400 U/g. Under these conditions, the hydrolysis efficiency of bovine bone collagen by Aa2_1884 reached 95.3%. The resultant hydrolysate contained 97.8% peptides, in which peptides with a molecular weight lower than 1000 Da and 500 Da accounted for 55.1% and 39.5%, respectively, indicating that the hydrolysate was rich in oligopeptides. These results indicate that Aa2_1884 likely has a promising potential application in the preparation of collagen oligopeptide-rich hydrolysate from bovine bone collagen, which may provide a feasible way for the high-value utilization of bovine bone collagen.

Active site architecture of an acetyl xylan esterase indicates a novel cold adaptation strategy.

SGNH-type acetyl xylan esterases (AcXEs) play important roles in marine and terrestrial xylan degradation, which are necessary for removing acetyl side groups from xylan. However, only a few cold-adapted AcXEs have been reported, and the underlying mechanisms for their cold adaptation are still unknown because of the lack of structural information. Here, a cold-adapted AcXE, AlAXEase, from the Arctic marine bacterium Arcticibacterium luteifluviistationis SM1504T was characterized. AlAXEase could deacetylate xylooligosaccharides and xylan, which, together with its homologs, indicates a novel SGNH-type carbohydrate esterase family. AlAXEase showed the highest activity at 30 °C and retained over 70% activity at 0 °C but had unusual thermostability with a Tm value of 56 °C. To explain the cold adaption mechanism of AlAXEase, we next solved its crystal structure. AlAXEase has similar noncovalent stabilizing interactions to its mesophilic counterpart at the monomer level and forms stable tetramers in solutions, which may explain its high thermostability. However, a long loop containing the catalytic residues Asp200 and His203 in AlAXEase was found to be flexible because of the reduced stabilizing hydrophobic interactions and increased destabilizing asparagine and lysine residues, leading to a highly flexible active site. Structural and enzyme kinetic analyses combined with molecular dynamics simulations at different temperatures revealed that the flexible catalytic loop contributes to the cold adaptation of AlAXEase by modulating the distance between the catalytic His203 in this loop and the nucleophilic Ser32. This study reveals a new cold adaption strategy adopted by the thermostable AlAXEase, shedding light on the cold adaption mechanisms of AcXEs.

Negative Regulation of the Differentiation of Flk2- CD34- LSK Hematopoietic Stem Cells by EKLF/KLF1.

Erythroid Krüppel-like factor (EKLF/KLF1) was identified initially as a critical erythroid-specific transcription factor and was later found to be also expressed in other types of hematopoietic cells, including megakaryocytes and several progenitors. In this study, we have examined the regulatory effects of EKLF on hematopoiesis by comparative analysis of E14.5 fetal livers from wild-type and Eklf gene knockout (KO) mouse embryos. Depletion of EKLF expression greatly changes the populations of different types of hematopoietic cells, including, unexpectedly, the long-term hematopoietic stem cells Flk2- CD34- Lin- Sca1+ c-Kit+ (LSK)-HSC. In an interesting correlation, Eklf is expressed at a relatively high level in multipotent progenitor (MPP). Furthermore, EKLF appears to repress the expression of the colony-stimulating factor 2 receptor ß subunit (CSF2RB). As a result, Flk2- CD34- LSK-HSC gains increased differentiation capability upon depletion of EKLF, as demonstrated by the methylcellulose colony formation assay and by serial transplantation experiments in vivo. Together, these data demonstrate the regulation of hematopoiesis in vertebrates by EKLF through its negative regulatory effects on the differentiation of the hematopoietic stem and progenitor cells, including Flk2- CD34- LSK-HSCs.

The Emerging Role of Sperm-Associated Antigen 6 Gene in the Microtubule Function of Cells and Cancer.

Accumulated evidence shows that sperm-associated antigen 6 (SPAG6) gene has multiple biological functions. It maintains the normal function of a variety of cells including ciliary/flagellar biogenesis and polarization, neurogenesis, and neuronal migration. Moreover, SPAG6 is found to be critically involved in auditory transduction and the fibroblast life cycle. Furthermore, SPAG6 plays an essential role in immuno-regulation. Notably, SPAG6 has been demonstrated to participate in the occurrence and progression of a variety of human cancers. New evidence shows that SPAG6 gene regulates tumor cell proliferation, apoptosis, invasion, and metastasis. Therefore, in this review, we describe the physiological function and mechanism of SPAG6 in human normal cells and cancer cells. We also highlight that SPAG6 gene may be an effective biomarker for the diagnosis of human cancer. Taken together, targeting SPAG6 could be a novel strategy for the treatment of human diseases including cancer.

Effective extraction with deep eutectic solvents and enrichment by macroporous adsorption resin of flavonoids from Carthamus tinctorius L.

In the present study, deep eutectic solvents (DESs) were prepared and firstly applied to extract flavonoids from Safflower using ultrasonic-assisted extraction (UAE), and DES2-UAE was selected as a green and efficient extraction method. The effects of extraction parameters on extraction efficiency (EE) of flavonoids were investigated by single-factor experiments and optimized using a Box-Behnken design (BBD). The optimal results were 56.37 mL/g liquid-solid ratio, 55.85 min extraction time, 41.44 °C extraction temperature and 188.55 W ultrasonic power, respectively. Under optimal extraction conditions, the highest EE of flavonoids (55.41 mg/g) was obtained. The verification experimental results were in good correlation with the predicted results. The adsorption and desorption experiments of flavonoids on five types of macroporous resins (NKA-2, AB-8, HPD-100, D-101 and S-8) were carried out, NKA-2 and S-8 showed higher adsorption/desorption capacities, successively followed by AB-8, D-101 and HPD-100. The adsorption behaviors were better explained by Langmuir isotherm model according to correlation coefficient on the basis of static adsorption test at different temperature. In conclusion, the developed DES2-UAE combined with macroporous resin enrichment can be an alternative method for the green and efficient extraction of bioactive flavonoids from plant materials.

Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma with a micropapillary pattern: cases report and literature review.

Xp11.2 translocation/transcription factor E3 (TFE3) gene fusion renal cell carcinoma (Xp11.2 translocation RCC) was first classified as a distinct type of renal tumor by the World Health Organization in 2004. However, its morphology and clinical manifestations often overlap with those of conventional RCCs. Moreover, a micropapillary pattern (MPP) comprising small papillary cell clusters surrounded by lacunar spaces has never been described in RCC. We compared the clinicopathological and prognostic characteristics of one patient with Xp11.2 translocation RCC exhibiting an MPP (TFE3-M) to those of four patients with conventional Xp11.2 translocation RCC (TFE3-N); all five tumors resembled conventional RCCs on gross pathology. All patients exhibited similar histologies, clinical manifestations, and prognoses, and all underwent radical nephrectomy. However, their characteristics differed significantly from those of other MPP-comprising neoplasms. Both tumor types were positive for TFE3 and vimentin; however, TFE3-M tumor cells expressed epithelial membrane antigen and human melanoma black-45 but not cluster of differentiation 10 (CD10), whereas the TFE3-N cells expressed P504S, CD10, and vimentin but not cytokeratin 7. Our RT-PCR analysis result showed that TFE3-N and TFE3-M tumor cells were identified expressing ASPSCR1-TFE3 and PRCC-TFE3 fusion genes, respectively. These findings suggest that TFE3-M should be classified as a histological subtype of Xp11.2 translocation RCC, although its relationship with other MPP-exhibiting neoplasms remains unclear. The histological characteristics of Xp11.2 translocation RCCs depend on MiT family transcription factors and their gene fusion partners. Xp11.2 translocation RCC should be considered for malignancies presenting with a particular pattern; such malignancies can be identified reliably by their morphological and immunohistochemical profiles.

Rational Recursion Operators for Integrable Differential-Difference Equations.

In this paper we introduce the concept of preHamiltonian pairs of difference operators, demonstrate their connections with Nijenhuis operators and give a criteria for the existence of weakly nonlocal inverse recursion operators for differential-difference equations. We begin with a rigorous setup of the problem in terms of the skew field of rational (pseudo-difference) operators over a difference field with a zero characteristic subfield of constants and the principal ideal ring of matrix rational (pseudo-difference) operators. In particular, we give a criteria for a rational operator to be weakly nonlocal. A difference operator is called preHamiltonian, if its image is a Lie subalgebra with respect to the Lie bracket on the difference field. Two preHamiltonian operators form a preHamiltonian pair if any linear combination of them is preHamiltonian. Then we show that a preHamiltonian pair naturally leads to a Nijenhuis operator, and a Nijenhuis operator can be represented in terms of a preHamiltonian pair. This provides a systematic method to check whether a rational operator is Nijenhuis. As an application, we construct a preHamiltonian pair and thus a Nijenhuis recursion operator for the differential-difference equation recently discovered by Adler and Postnikov. The Nijenhuis operator obtained is not weakly nonlocal. We prove that it generates an infinite hierarchy of local commuting symmetries. We also illustrate our theory on the well known examples including the Toda, the Ablowitz-Ladik, and the Kaup-Newell differential-difference equations.

Teroxirone motivates apoptotic death in tumorspheres of human lung cancer cells.

Therapy by targeting cancer stem cells (CSCs) is an eligible method to eradicate malignant human tumors. A synthetic triepoxide derivative, teroxirone, was reported effective against the growth of human lung cancer cells by injuring cellular mitochondria functions. And yet it remains unclear if the residual but malicious CSCs can be effectively dissipated following treatment. The current study further affirmed that teroxirone inhibited the propagation of CSCs as enriched from NSCLC cells by inducing p53 that lead to ultimate apoptosis. More evidence supported that the reduced stemness of the spheroids was associated with apoptotic death. The results consolidate the notion that teroxirone is a viable and effective therapeutic agent for eradicating human lung cancer.

Teroxirone suppresses growth and motility of human hepatocellular carcinoma cells.

AIMS: The prevalent human hepatocellular carcinoma (HCC) is a leading cause of global cancer-related mortality. The small molecular weight triepoxide derivative, 1,3,5-triazine-2,4,6(1H,3H,5H)-tri-one-1,3,5-tri-(oxiranylmethyl) (teroxirone), has been proved effective against the proliferation of lung cancer cells. The purpose is to further examine if teroxirone regulate growth and metastatic potential of HCC cells with aims at disclosing more of the reaction mechanisms. MAIN METHODS: Measurements of cell viability and flow cytometry were conducted to test sensitivities of teroxirone against HCC cells. The signaling pathway leading to apoptotic death was unraveled by Western blotting analysis. The metastatic progression was evaluated by cell-based phenotype assay that included migration, invasion, gelatin zymography and wound assay. The in vivo drug efficiency was done in immune-deficient mice with the established xenograft tumors. KEY FINDINGS: Teroxirone inhibited growth of HCC cells, but not hepatic cells. The drug induced apoptosis in HCC cells bearing mutant p53. Pretreatment of caspase-3 inhibitor restored cell viabilities by suppressing extrinsic pathway-mediated cell death. More experiments suggested that sub-apoptotic concentrations of teroxirone mitigated migration, invasion and wound healing of HCC cells. The drug reduced growth of the xenograft tumors as established in animal models by activating apoptotic death. SIGNIFICANCE: The findings asserted that teroxirone is an eligible addition to the existing options as an anticancer agent to eliminate HCC.

Generalizations of the short pulse equation.

We classify integrable scalar polynomial partial differential equations of second order generalizing the short pulse equation.

Ollier disease: two case reports and a review of the literature.

Ollier disease is a rare tumor with unclear clinicopathological features and pathogenesis. We herein report two cases of Ollier disease in a 15-year-old boy and a 66-year-old man. We analyzed the clinicopathological, radiographical, and histochemical characteristics of Ollier disease in these two cases. Furthermore, we reviewed the literature to better understand the clinicopathological features of this disease. The boy had multiple enchondromas in the metaphysis and upper region of the left femur, and his left leg is short naturally. The 66-year-old man had multiple enchondromas in his left ribs and lower segment of the left femur. He was sent to the hospital because of pathological fracture of the ribs. In addition, he was diagnosed with gastric cancer 4 years before visiting an orthopedic clinic. Ollier disease is a rare bone disease that often renders a typical asymmetrical distribution and is confined to the appendicular skeleton. It is known as a benign bone tumor and has a high risk of malignant transformation into a chondrosarcoma (5%-50%). Correct diagnosis requires radiographic, histochemical, and morphological analyses. Better understanding of the clinical manifestations and pathological features can improve the diagnosis and prevent malignant transformation and deformity, especially in adolescent patient.

A triazole-conjugated benzoxazone induces reactive oxygen species and promotes autophagic apoptosis in human lung cancer cells.

Numerous approaches suggested that compounds with conjugated triazole moieties or benzoxazone pharmacores are effective to antagonize proliferation of human tumors. The current study reported that a synthetic triazole-conjugated benzoxazone, 4-((5-benzyl-1H-1,2,3-triazol-3-yl)-methyl)-7-methoxy-2H-benzo[b][1,4]-oxazin-3(4H)-one (BTO), inhibited growth rates of human non-small cell lung cancer cells. The cytotoxicity can be enhanced with increasing drug concentrations. More evidence supported that the induced reactive oxygen species lead to ultimate apoptotic cell death by recruiting autophagy. The mechanistic pathway as elucidated involved tumor suppressor p53 activation and LC3-1 conversion followed by PARP and procaspase-3 cleavage. Autophagy inhibition reverted apoptotic death and restored cell viabilities. BTO suppressed the development of A549 cell xenograft tumors by activating autophagy and apoptosis simultaneously. As an efficient tumor growth inhibitor with relatively small molecular weight, BTO is a viable addition to the existing list of lung cancer treatment.

Nosocomial Infection Surveillance in a Tuberculosis Specialized Hospital in China.

Nosocomial infections (NIs) are a critical issue affecting the quality of healthcare. In this study, we performed a retrospective study to explore the incidence rates, mortality rates, and microbial spectrum of NIs in Beijing Chest Hospital, a tuberculosis (TB) specialized hospital in China. Our data demonstrate that the overall incidence rate of inpatients with NIs slightly decreased from 2012 to 2016, which may be associated with the implementation of hand hygiene measures, while the mortality rates associated with NI did not significantly change. In addition, the species distribution of NIs was quite different from that presented in previous reports, and Klebsiella pneumoniae was the most frequently isolated microorganism.

Reactive oxygen species-driven mitochondrial injury induces apoptosis by teroxirone in human non-small cell lung cancer cells.

Teroxirone as an anticancer agent is used to treat human lung cancer by inducing apoptotic cell death. Previous studies have demonstrated that the status of the tumor suppressor p53 determined the onset of apoptotic cell death in human non-small cell lung cancer cells (NSCLC). In order to further understand the underlying mechanisms of lung cancer, the present study explored the targets of teroxirone. By including antioxidants, the present study analyzed changes in cell proliferation, cell cycle division, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), expression of apoptosis markers and cytochrome c distribution. Subsequent to a 12 h treatment with low concentrations of teroxirone, MMP was suppressed, followed by ROS production and apoptosis in lung cancer cells carrying wild type p53. N-acetylcysteine inhibited apoptotic cell death. The depleted expression of p53, reduction of apoptosis-associated active caspase-3 and poly ADP-ribose polymerase cleavage with resurgence of the pro-survival signal protein kinase B, all demonstrated an antioxidant-mediated reduction of apoptosis by teroxirone. The diminished ROS intensity inhibited the release of mitochondrial cytochrome c and DNA damage. The present study provided evidence that teroxirone treatment induced the ROS-activated intrinsic apoptotic pathway, which led to cell death in human NSCLC cells.

A potent indolylquinoline alleviates growth of human lung cancer cell tumorspheres.

To fight cancer at its roots by targeting cancer stem cells is a promising approach for therapy. Previously, an indolylquinoline derivative, 3-((7-ethyl-1H-indol-3-yl)-methyl)-2-methylquinoline (EMMQ), was reported effectively inhibiting the growth of lung cancer cells through impairment of cellular mitochondria functions. To address more on drug efficiency, the study further exploited if EMMQ can impede the propagation of tumorspheres stemmed from non-small cell lung cancer cells. EMMQ inhibited proliferation of spheroids in culture. In animal models, administration of the drug attenuated the spheroid tumorigenicity. The activated apoptosis alleviated growth of xenograft tumors in immune-deficient mice as established by the enriched tumorspheres. More evidence suggested that the reduced stemness of the spheroid tumors is attributed to apoptotic death. The findings supported that EMMQ is an eligible approach to eradicate the minor but tumorigenic lung cancer tumorspheres.

An indolylquinoline derivative activates DNA damage response and apoptosis in human hepatocellular carcinoma cells.

Human liver cancer is one of the most frequently diagnosed cancers worldwide. The development of resistance to therapy limits the application against the disease. To improve treatment, new effective anticancer agents are constantly pursued. Previously, we reported that an indolylquinoline, 3-((7-ethyl-1H-indol-3-yl)-methyl)-2-methylquinoline (EMMQ), is effective in suppressing the growth of human lung cancer by impairing mitochondria functions. The present study revealed that EMMQ inhibited cell growth and induced apoptosis in liver cancer cells, but not in normal cells. This study demonstrated that EMMQ induced DNA damage by activating p53 and γ-H2AX and cell arrest by suppressing cyclin D1 and CDK2. Damaged DNA injured mitochondrial functions by lowering the membrane potential and producing reactive oxygen species. The subsequent mitochondrial cytochrome c release attenuated pro-survival signals and increased apoptotic characteristics. Introduction of p53 shRNA abrogated drug effects by reducing DNA damage while maintaining mitochondria integrity. In brief, the study demonstrates that the effectiveness of EMMQ accentuated apoptosis of hepatocarcinoma cells by activating p53. Based on these collective findings, the study offered a new perspective of EMMQ that was shown to be a promising candidate to treat liver cancer.