Identification and validation of CCL5 as a key gene in HIV infection and pulmonary arterial hypertension.

Background: The relationship between human immunodeficiency virus (HIV) infection and pulmonary arterial hypertension (PAH) has garnered significant scrutiny. Individuals with HIV infection have a higher risk of developing PAH. However, the specific mechanism of HIV-associated PAH remains unclear. Our study aims at investigating the shared biomarkers in HIV infection and PAH and predicting the potential therapeutic target for HIV-associated PAH. Methods: Data for HIV infection and PAH were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) analysis was performed to detect shared genes in HIV infection and PAH. Enrichment analysis was conducted to identify the function of common DEGs. Protein-protein interaction (PPI) analysis was used to detect key genes. These crucial genes were subsequently verified by RT-qPCR. Finally, candidate drugs were identified by using the Drug Signatures Database (DSigDB). Results: Nineteen common DEGs were identified in HIV infection and PAH. Enrichment analysis exhibited that the functions of these genes were mainly enriched in inflammatory responses, mainly including cellular immunity and interaction between viral proteins and cytokines. By constructing PPI networks, we identified the key gene CC-type chemokine ligand 5 (CCL5), and we verified that CCL5 was highly expressed in hypoxia induced human pulmonary artery endothelial cells (hPAECs) and human pulmonary artery smooth muscle cells (hPASMCs). In addition, we predicted 10 potential drugs targeting CCL5 by Autodock Vina. Conclusion: This study revealed that CCL5 might be a common biomarker of HIV infection and PAH and provided a new therapeutic target for HIV-associated PAH. However, further clinical validation is still indispensable.

A comprehensive single-cell RNA transcriptomic analysis identifies a unique SPP1+ macrophages subgroup in aging skeletal muscle.

Senescence of skeletal muscle (SkM) has been a primary contributor to senior weakness and disability in recent years. The gradually declining SkM function associated with senescence has recently been connected to an imbalance between damage and repair. Macrophages (Mac) are involved in SkM aging, and different macrophage subgroups hold different biological functions. Through comprehensive single-cell transcriptomic analysis, we first compared the metabolic pathways and biological functions of different types of cells in young (Y) and old (O) mice SkM. Strikingly, the Mac population in mice SkM was also explored, and we identified a unique Mac subgroup in O SkM characterized by highly expressed SPP1 with strong senescence and adipogenesis features. Further work was carried out on the metabolic and biological processes for these Mac subgroups. Besides, we verified that the proportion of the SPP1+ Mac was increased significantly in the quadriceps tissues of O mice, and the senotherapeutic drug combination dasatinib + quercetin (D + Q) could dramatically reduce its proportion. Our study provides novel insight into the potential role of SPP1+ Mac in SkM, which may serve as a senotherapeutic target in SkM aging.

Revisiting an old relationship: the causal associations of the ApoB/ApoA1 ratio with cardiometabolic diseases and relative risk factors-a mendelian randomization analysis.

BACKGROUND: It has been confirmed that the ApoB/ApoA1 ratio is closely associated with the incidence of cardiometabolic diseases (CMD). However, due to uncontrolled confounding factors in observational studies, the causal relationship of this association remains unclear. METHODS: In this study, we extracted the ApoB/ApoA1 ratio and data on CMD and its associated risk factors from the largest European Genome-Wide Association Study. The purpose was to conduct Mendelian Randomization (MR) analysis. The causal relationship between the ApoB/ApoA1 ratio and CMD was evaluated using both univariable and multivariable MR analyses. Furthermore, bidirectional MR analysis was performed to estimate the causal relationship between the ApoB/ApoA1 ratio and risk factors for CMD. The final verification confirmed whether the ApoB/ApoA1 ratio exhibits a mediating effect in CMD and related risk factors. RESULTS: In terms of CMD, a noteworthy correlation was observed between the increase in the ApoB/ApoA1 ratio and various CMD, including ischemic heart disease, major adverse cardiovascular events, aortic aneurysm, cerebral ischemic disease and so on (all PFDR<0.05). Meanwhile, the ApoB/ApoA1 ratio was significantly associated with CMD risk factors, such as hemoglobin A1c, fasting insulin levels, waist-to-hip ratio, sedentary behavior, and various others, demonstrating a notable causal relationship (all PFDR<0.05). Additionally, the ApoB/ApoA1 ratio played a mediating role in CMD and relative risk factors. CONCLUSIONS: This MR study provides evidence supporting the significant causal relationship between the ApoB/ApoA1 ratio and CMD and its risk factors. Moreover, it demonstrates the mediating effect of the ApoB/ApoA1 ratio in CMD and its risk factors. These findings suggest that the ApoB/ApoA1 ratio may serve as a potential indicator for identifying the risk of developing CMD in participants.

Gut microbiota and risk of endocarditis: a bidirectional Mendelian randomization study.

Background: The associations between gut microbiota and cardiovascular disease have been reported in previous studies. However, the relationship between gut microbiota and endocarditis remains unclear. Methods: A bidirectional Mendelian randomization (MR) study was performed to detect the association between gut microbiota and endocarditis. Inverse variance weighted (IVW) method was considered the main result. Simultaneously, heterogeneity and pleiotropy tests were conducted. Results: Our study suggests that family Victivallaceae (p = 0.020), genus Eubacterium fissicatena group (p = 0.047), genus Escherichia Shigella (p = 0.024), genus Peptococcus (p = 0.028) and genus Sellimonas (p = 0.005) play protective roles in endocarditis. Two microbial taxa, including genus Blautia (p = 0.006) and genus Ruminococcus2 (p = 0.024) increase the risk of endocarditis. At the same time, endocarditis has a negative effect on genus Eubacterium fissicatena group (p = 0.048). Besides, no heterogeneity or pleiotropy was found in this study. Conclusion: Our study emphasized the certain role of specific gut microbiota in patients with endocarditis and clarified the negative effect of endocarditis on gut microbiota.

Comparison of Third-Generation Sequencing and Routine Polymerase Chain Reaction in Genetic Analysis of Thalassemia.

CONTEXT.­: Thalassemia is the most widely distributed monogenic autosomal recessive disorder in the world. Accurate genetic analysis of thalassemia is crucial for thalassemia prevention. OBJECTIVE.­: To compare the clinical utility of a third-generation sequencing-based approach termed comprehensive analysis of thalassemia alleles with routine polymerase chain reaction (PCR) in genetic analysis of thalassemia and explore the molecular spectrum of thalassemia in Hunan Province. DESIGN.­: Subjects in Hunan Province were recruited, and hematologic testing was performed. Five hundred four subjects positive on hemoglobin testing were then used as the cohort, and third-generation sequencing and routine PCR were used for genetic analysis. RESULTS.­: Of the 504 subjects, 462 (91.67%) had the same results, whereas 42 (8.33%) exhibited discordant results between the 2 methods. Sanger sequencing and PCR testing confirmed the results of third-generation sequencing. In total, third-generation sequencing correctly detected 247 subjects with variants, whereas PCR identified 205, which showed an increase in detection of 20.49%. Moreover, α triplications were identified in 1.98% (10 of 504) hemoglobin testing-positive subjects in Hunan Province. Seven hemoglobin variants with potential pathogenicity were detected in 9 hemoglobin testing-positive subjects. CONCLUSIONS.­: Third-generation sequencing is a more comprehensive, reliable, and efficient approach for genetic analysis of thalassemia than PCR, and allowed for a characterization of the thalassemia spectrum in Hunan Province.

Causal effect of body mass index and physical activity on the risk of joint sports injuries: Mendelian randomization analysis in the European population.

BACKGROUND: Observational studies can suggest potential associations between variables but cannot establish a causal effect on their own. This study explored the causal associations between body mass index (BMI), physical activity (PA), and joint sports injuries. METHODS: We conducted two-sample Mendelian randomization (MR) using publicly accessed genome-wide association studies (GWAS) datasets to investigate the causal effects of BMI and PA on joint sports injury risk. The inverse-variance weighted method was believed to be the primary MR analysis. Subsequently, sensitivity, pleiotropy, and heterogeneity analyses were employed to estimate the reliability of the results of the current research. RESULTS: Genetically predicted increased BMI was causally related to the higher sports injury risk of the ankle-foot (OR 1.23, 95% CI 1.09-1.37, p = 4.20E-04), knee (OR 1.32, 95% CI 1.21-1.43, p = 1.57E-11), and shoulder (OR 1.23, 95% CI 1.08-1.40, p = 1.28E-03). Further, the mentioned effects were validated using another set of GWAS data on BMI. Similar causal linkages were exhibited between increased BMI and the growing risk of sports injuries of the ankle-foot (OR 1.34, 95% CI 1.13-1.60, p = 9.51E-04), knee (OR 1.26, 95% CI 1.09-1.45, p = 1.63E-03), and shoulder (OR 1.35, 95% CI 1.09-1.67, p = 5.66E-03). Additionally, accelerometer-based PA measurement (overall average acceleration) (AccAve) was negatively related to sports injuries of the ankle-foot (OR 0.93, 95% CI 0.87-0.99, p = 0.046) and lumbar spine (OR 0.68, 95% CI 0.51-0.92, p = 0.012). Furthermore, we verified that the effect of AccAve on the risk of injury at the ankle-foot still had statistical significance after adjusting BMI. Results were verified as reliable under all sensitive analyses. CONCLUSIONS: This research determined that a higher BMI could raise the sports injury risk of the ankle-foot, knee, and shoulder, while an overall average acceleration PA could reduce the injury risk of the ankle-foot and lumbar spine. These conclusions contribute to a greater knowledge of the roles of BMI and PA in the mechanism of joint sports injuries and offer several suggestions for patients and clinicians.

A novel protective role of lipoxin in inhibiting diabetic vascular calcification via YAP signalling: Health prevention and regulation.

Vascular calcification is highly prevalent in diabetes patients, with detrimental consequences and no effective prevention and treatment strategies are currently available. Though the protective effect of lipoxin (LX) against vascular diseases has been demonstrated, its effect on diabetic vascular calcification remains unknown. AGEs dose-dependently induced calcification and the expression of osteogenesis-related markers, coupled with the activation of yes-associated protein (YAP). Mechanistically, YAP activation enhanced the AGE-induced osteogenic phenotype and calcification, but inhibition of YAP signalling alleviated this response. Further, an in vivo diabetic mouse model was established using a combination of a high-fat diet and multiple formulations of low-dose streptozotocin. Consistent with the in vitro results, diabetes promoted YAP expression and its subcellular localization in the nucleus in the arterial tunica media. The results demonstrate that LX attenuates the trans-differentiation and calcification of VSMCs in diabetes mellitus via YAP signalling, suggesting LX to be a potent therapeutic for preventing diabetic vascular calcification.

Circ_0001052 promotes cardiac hypertrophy via elevating Hipk3.

Cardiac hypertrophy (CH) is a crucial risk factor for sudden death. Circular RNAs (circRNAs) exert significant effects in various biological and pathological processes. Circ_0001052 is sourced from Hipk3 (homeodomain-interacting protein kinase 3) and is reported to aggravate myocardial fibrosis. The purpose of the current study was to clarify the role and mechanism of circ-Hipk3 in CH. Transverse aortic constriction (TAC) was used to create an in vivo CH model, and angiotensin II (Ang II) therapy was used to create an in vitro CH model in cardiomyocytes (CMs). It was uncovered that circ_0001052 exerted pro-hypertrophic effects in Ang II-treated CMs. Next, the circular characteristics of circ_0001052 were verified, and we identified that circ_0001052 positively regulated Hipk3. Hipk3 exerted the same functions as circ_0001052 did. It is significant to note that circ_0001052 acted as the ceRNA of Hipk3 by sponging miR-148a-3p and miR-124-3p. According to rescue assays, miR-148a-3p and miR-124-3p partially reversed the effects of circ_0001052. Further, we testified that circ_0001052 recruited Srsf1 to stabilize Hipk3. Finally, rescue assays demonstrated that circ_0001052 promoted CH via up-regulation of Hipk3. In conclusion, our work unveiled that circ_0001052 promoted hypertrophic effects through elevating Hipk3 via sponging miR-148a-3p and miR-124-3p and recruiting Srsf1.

A landscape of Long non-coding RNAs reveals the leading transcriptome alterations in murine aorta during aging.

Considerable studies have given convincing evidence of a forefront position for vascular aging in preventing cardiovascular disease. Various functions of Long non-coding RNAs (lncRNAs) are becoming increasingly distinct in aging-related diseases. This study aims at a better insight into the expression profile and mechanisms of lncRNAs in vascular senescence. High-throughput sequencing was used to detect the differential expression (DE) of lncRNAs and mRNAs in the aorta of 96 W and 8 W-old mice, while 1423 lncRNAs and 80 mRNAs were differentially expressed. By performing GO and KEGG enrichment analysis, we found that DE lncRNAs were mainly involved in purine metabolism and cGMP-PKG signaling pathways. In addition, a co-expression functional network of DE lncRNAs and DE mRNAs was constructed, and ENSMUST00000218874 could interact with 41 DE mRNAs, suggesting that it may play an essential role in vascular senescence. This study reveals DE lncRNAs in naturally aging vascular, which may provide new ideas and targets for aging-related cardiovascular diseases.

Stilbenes with potent cytotoxicity from the seedcases of Paeonia suffruticosa Andrews.

Stilbenes (based on the 1,2-diphenylethylene skeleton) are a class of plant polyphenols with rich structural and bioactive diversity. Twenty-six stilbenes, including five undescribed compounds (7,8-dioxy-4,3',5'-trihydroxystilbene, trans-13'-methoxygnetin H, suffruticosol E, paestibenetrimerols A and B), were isolated from the seedcases of Paeonia suffruticosa Andrews. Their structures were elucidated by spectroscopic analyses and comparison with previously reported data. The absolute configurations of trans-13'-methoxygnetin H, suffruticosol E, paestibenetrimerols A and B were assigned from their respective electronic circular dichroism (ECD) spectra. Additionally, the structures of known compounds suffruticosols A, B and rockiol B were revised and the absolute configurations of them, and along with (+)-davidiol A, were also further determined by ECD. The isolated compounds, trans-gnetin H, cis-gnetin H and suffruticosol E, were found to have potent cytotoxicity against the DU-145 and MDA-MB-231 cell lines with IC50 values of 4.89-8.61 µM. The preliminary antitumor structure-activity relationship of these stilbenes is discussed as well.

Cytotoxic alkaloids from the fruit pods of Macleaya microcarpa.

19 compounds, including seven previously undescribed alkaloids ((-)-macleayin K (1), (+)-macleayin K (2), macleayin M (3), macleayin N (4), macleayin L (5), macleayin O (6), oxohydrastinine A (7), one new natural product (8), and 11 known compounds, were isolated from the fruit pods of Macleaya microcarpa. Their structures were defined based on NMR, HRESIMS, and electronic circular dichroism (ECD) data. A network pharmacology approach combined with molecular docking and in vitro validation was performed to determine the bioactivity, key targets of the 19 compounds against breast cancer (BC) and cervical cancer (CC). EGFR and PIK3CA could become potential therapeutic targets based a network pharmacology. Moreover, molecular docking suggested that the 19 compounds combined well with EGFR and PIK3CA, respectively. Their cytotoxicity of selected compounds was tested against the MCF-7 and HeLa cells, and the preliminary structure-activity relationship is discussed. Compounds 1 (IC50: 6.00 µM) and 2 (IC50: 6.82 µM) exhibited strong inhibitory activity against the HeLa cells and are worthy of further study.

Vaspin alleviates the lncRNA LEF1-AS1-induced osteogenic differentiation of vascular smooth muscle cells via the Hippo/YAP signaling pathway.

Vascular calcification (VC) is closely related to higher cardiovascular mortality and morbidity, and vascular smooth muscle cell (VSMC) switching to osteogenic-like cells is crucial for VC. LncRNA LEF1-AS1 promotes atherosclerosis and dental pulp stem cells calcification, while its role in VC remains unknown. Visceral adipose tissue-derived serine protease inhibitor (vaspin) is an adipokine regulating bone metabolism. However, the relationship between vaspin and VC is still unclear. We aimed to explore the role of LEF1-AS1 on VSMC osteogenic transition, whether vaspin inhibited LEF1-AS1-mediated osteogenic differentiation of VSMCs, and the responsible mechanism. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis indicated that LEF1-AS1 overexpression significantly upregulated osteogenic marker Runt-related transcription factor-2 (RUNX2) level and downregulated VSMC contractile marker α-smooth muscle actin (α-SMA) level. Alizarin red staining, alkaline phosphatase (ALP) staining, ALP activity assay, and calcium content assay also suggested that LEF1-AS1 overexpression promoted calcium deposition in VSMCs. However, vaspin treatment abolished this phenomenon. Mechanistically, LEF1-AS1 markedly decreased phosphorylated YAP level, while vaspin reversed LEF1-AS1-induced phosphorylated YAP decline. Our results revealed that LEF1-AS1 accelerated the osteogenic differentiation of VSMCs by regulating the Hippo/YAP pathway, while vaspin eliminated the LEF1-AS1-meditated VSMCs osteogenic phenotype switch.

Flavonolignans and biflavonoids from Cephalotaxus oliveri exert neuroprotective effect via Nrf2/ARE pathway.

Plants of the Cephalotaxus genus are rich in structurally diverse and naturally bioactive components, while limited studies have been reported for Cephalotaxus oliveri. Two undescribed flavonolignans and four undescribed biflavonoids, as well as thirteen known compounds, were isolated from the twigs and leaves of C. oliveri. Their structures were characterized by spectroscopic data analysis, and the absolute configurations were determined by electronic circular dichroism (ECD) calculations. All the isolated compounds were assayed for their neuroprotective activity against hydrogen peroxide (H2O2)-induced SH-SY5Y cell injury. All six undescribed compounds were effective to some degree, and umcephabiflovin B, apigenin 5-O-α-L-rhamnopyranosyl-(1 â†’ 2)-6″-acetyl-ß-D-glucopyranoside, and apigenin 7-O-ß-D-glucoside exhibited good neuroprotective activity. Umcephabiflovin B protected SH-SY5Y cells against H2O2-induced neurotoxicity by repressing oxidative stress and apoptosis and by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant-response element (ARE) pathway.

[Health economic evaluation of four prenatal screening strategies for Down syndrome in Changsha, China].

OBJECTIVE: To compare the clinical application and health economic values of non-invasive prenatal testing (NIPT) and second trimester serum screening (STSS). METHODS: A retrospective analysis was carried out on 54 026 singleton pregnant women undergoing NIPT and STSS from March 1, 2018 to December 31, 2019 in Changsha Maternal and Child Health Care Hospital. For pregnant women with high-risk results of NIPT, prenatal diagnosis and follow-up of pregnancy outcomes were conducted. The data was grouped to 4 screening models, and their cost-benefit was analyzed. RESULTS: The sensitivity, specificity and positive predictive value of NIPT were all higher than STSS. Screening models 1 to 4 have prevented the birth of 71, 29, 52 and 54 patients with Down syndrome, respectively. The safety index of screening models 1 to 4 were 0.0036, 0.3944, 02215 and 0.1281, respectively. When the price of NIPT was decreased to 600 RMB, the cost-benefit of the screening models 1 to 4 was 0.46, 0.65, 0.44 and 0.40 million RMB, respectively. CONCLUSION: NIPT has a better detection performance than STSS. When the price of NIPT is 600 RMB, screening model 1 has the best screening effect and the highest accuracy, safety index and health economical value.

Long Noncoding RNA SBF2-AS1 Promotes Abdominal Aortic Aneurysm Formation through the miRNA-520f-3p/SMARCD1 Axis.

Abdominal aortic aneurysm (AAA) is a chronic vascular inflammatory disease. The regulatory mechanisms during AAA formation remain unclear. Bone marrow stem cells (BMSCs) are pluripotent cells capable of regulating the progression of various diseases by delivering exosomes and exosomal lncRNAs. In this study, we investigated its function in AAA by isolating BMSC exosome-derived lncRNA SBF2-AS1. The results showed that BF2-AS1 could be transferred to vascular smooth muscle cells (VSMCs) and human aortic VSMCs (HASMCs) via BMSC-derived exosomes. Depletion of SBF2-AS1 enhanced the cell viability and proliferation of VSMCs. Conversely, SBF2-AS1 knockdown inhibited VSMC apoptosis. Caspase-3 activity was inhibited by depletion of SBF2-AS1, whereas overexpression of SBF2-AS1 in VSMC promoted Caspase-3 activity. SBF2-AS1 enhances SMARCD1 expression by forming miR-520f-3p in VSMC and HASMC. Overexpression of SMARCD1 or miR-520f-3p inhibitor reversed cell viability and caspase-3 activity mediated by SBF2-AS1 depletion in VSMC and HASMC. Therefore, BMSC exosome-derived SBF2-AS1 promotes AAA formation through the miRNA-520f-3p/SMARCD1 axis. Targeting SBF2-AS1 could serve as a promising therapeutic strategy for AAA.

Cephalotaxine-type and homoerythrina-type alkaloids with antiproliferative effects from Cephalotaxus fortunei.

Twenty-two cephalotaxine-type and ten homoerythrina-type alkaloids, including seven previously undescribed ones, were isolated from the twigs and leaves and the seed kernels of Cephalotaxus fortunei. Their structures were established by spectroscopic analysis, single crystal X-ray diffraction, and ECD calculation methods. Cephalofortunine A ß-N-oxide (1) is the first nitrogen-oxidized homoerythrina-type alkaloid. The isolated compounds were evaluated for their in vitro antiproliferative effects against two human leukemia cell lines (THP-1 and K562). All compounds showed different levels of antiproliferation in THP-1 and K562 cells with GI50 values of 0.24-29.55 µM. Hainanensine (31) was the most active against two cancer cell lines with GI50 values of 0.24 ± 0.07, and 0.29 ± 0.01 µM, respectively.

MicroRNA miR-331-3p suppresses osteosarcoma progression via the Bcl-2/Bax and Wnt/ß-Catenin signaling pathways and the epithelial-mesenchymal transition by targeting N-acetylglucosaminyltransferase I (MGAT1).

Osteosarcoma (OS) is a high-grade malignant disease that is a prevalent primary malignant sarcoma of the bone. The purpose of this investigation was to therefore elucidate the association between miR-331-3p and OS development and to identify a potential underlying mechanism. Key genes involved in OS were selected using GSE65071 dataset from the Gene Expression Omnibus (GEO) database and Gene Expression Profiling Interactive Analysis (GEPIA). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting were conducted to detect miR-331-3p, MGAT1, the epithelial-mesenchymal transition (EMT), Bcl-2/Bax and Wnt/ß-Catenin signaling pathways related proteins. Dual-luciferase reporter assay and TargetScan were used for validating interaction between MGAT1 mRNA and miR-331-3p. Biological effects of miR-331-3p and MGAT1 on OS cells were detected employing MTT, Transwell, wound healing and flow cytometry, respectively. MiR-331-3p was under-expressed in OS, and up-regulation or inhibition of its expression could significantly inhibit or promote the malignant phenotypes of OS cells. Furthermore, we found that MGAT1, a target of miR-331-3p, had elevated expression in OS. Interestingly, MGAT1 could partially alleviate the effect of miR-331-3p in vitro. Collectively, miR-331-3p acts as an critical tumor suppressor through inhibiting MGAT1, results in suppressed Wnt/ß-Catenin pathway and decreased proliferation of OS cells; leads to increased apoptosis via Bcl-2/Bax pathway and inhibited migration and invasion ability via the EMT.

Ubiquitin specific peptidase 11 as a novel therapeutic target for cancer management.

Ubiquitination is a critical biological process in post-translational modification of proteins and involves multiple signaling pathways in protein metabolism, apoptosis, DNA damage, cell-cycle progression, and cancer development. Deubiquitinase, a specific enzyme that regulates the ubiquitination process, is also thought to be closely associated with the development and progression of various cancers. In this article, we systematically review the emerging role of the deubiquitinase ubiquitin-specific peptidase 11 (USP11) in many cancer-related pathways. The results show that USP11 promotes or inhibits the progression and chemoresistance of different cancers, including colorectal, breast, ovarian, and hepatocellular carcinomas, via deubiquitinating several critical proteins of cancer-related pathways. We initially summarize the role of USP11 in different cancers and further discuss the possibility of USP11 as a therapeutic strategy.

Abietane diterpenes from the twigs and leaves of Cephalotaxus oliveri Mast. with antitumor activity.

Twenty one abietane diterpenes were isolated from Cephalotaxus oliveri Mast. The structures of 7 undescribed diterpenoids, named cephaloliverins A-G, were elucidated via spectroscopic data interpretation and electronic circular dichroism (ECD) analysis. The isolated diterpenoids were evaluated for their cytotoxicity against three kinds of human tumor cell lines (MCF-7, HepG2, and A549). Metaglyptin A was the most active with IC50 values of 16.34, 15.63 and 21.33 µM and was further investigated for colony formation and apoptosis in HepG2 cells.

Anti-tumor alkaloids from Peganum harmala.

Six alkaloids peharmalines F-K, along with 14 known ones, were isolated from the aerial part of Peganum harmala L.. The structures of the isolated compounds were determined based on their HR-ESI-MS data, extensive NMR spectroscopic analyses, and ECD calculations. 3-(4-Hydroxyphenyl)quinoline exhibited potent antiproliferative activity against the HepG-2 cell lines with an IC50 value of 3.05 µM. Norharmane displayed a moderate inhibition against A549 and HepG-2 cells with IC50 values of 16.45 µM and 17.27 µM, respectively.