Comparative Study of Antiproliferative Activity in Different Plant Parts of Phaleria macrocarpa and the Underlying Mechanism of Action.

Phaleria macrocarpa is a medicinal plant widely used in Indonesian folk medicine to treat several diseases, including cancer. However, the comparative evaluation of various plant parts of P. macrocarpa has not been studied for their anticancer properties on breast cancer. The study aimed to assess the antiproliferative activity of the ethanol extract of various parts of Phaleria macrocarpa against T47D human breast cancer cell lines. Several parts of P. macrocarpa, including pericarp, mesocarp, seed, and leaf, were used to determine the most potent plant part to inhibit the growth of T47D cells. The cytotoxic effects of each plant part were evaluated by WST-1 assay. The apoptotic level of T47D cells was determined by annexin V-FITC-PI and DNA fragmentation assay. Propidium iodide staining and the CFSE assay were used to examine the effect of each extract on cell cycle distribution and cell division, respectively. The relative number of caspase-3, Bax, and Bcl-2 was analyzed by flow cytometry technique. WST-1 assay revealed that P. macrocarpa leaves exhibited the most potent antiproliferative activity (p < 0.05) compared to other plant parts with selectivity only to T47D cells. P. macrocarpa leaves extract effectively induced apoptosis, inhibited proliferation, and arrested the cell cycle of T47D cells. The relative number of caspase-3 was significantly (p < 0.05) increased after being treated with P. macrocarpa leaf extract. P. macrocarpa leaf extract also leads to the dose-dependent accumulation in the Bax/Bcl-2 ratio due to upregulation of Bax and downregulation of Bcl-2. The overall results indicated that P. macrocarpa leaves could inhibit the proliferation of T47D cells and trigger apoptosis through caspase-3 activation and Bax/Bcl regulation. Therefore, P. macrocarpa leaves can be used for breast cancer therapy.

Rhizomucor miehei lipase immobilized on reinforced chitosan-chitin nanowhiskers support for synthesis of eugenyl benzoate.

An alternative environmentally benign support was prepared from chitosan-chitin nanowhiskers (CS/CNWs) for covalent immobilization of Rhizomucor miehei lipase (RML) to increase the operational stability and recyclability of RML in synthesizing eugenyl benzoate. The CS/CNWs support and RML-CS/CNWs were characterized using X-ray diffraction, fluorescent microscopy, and Fourier transform infrared spectroscopy. Efficiency of the RML-CS/CNWs was compared to the free RML to synthesize eugenyl benzoate for parameters: reaction temperature, stirring rate, reusability, and thermal stability. Under optimal experimental conditions (50°C, 250 rpm, catalyst loading 3 mg/mL), a twofold increase in yield of eugenyl benzoate was observed for RML-CS/CNWs as compared to free RML, with the former achieving maximum yield of the ester at 62.1% after 5 hr. Results demonstrated that the strategy adopted to prepare RML-CS/CNWs was useful, producing an improved and prospectively greener biocatalyst that supported a sustainable process to prepare eugenyl benzoate. Moreover, RML-CS/CNWs are biodegradable and perform esterification reactions under ambient conditions as compared to the less eco-friendly conventional acid catalyst. This research provides a facile and promising approach for improving activity of RML in which the resultant RML-CS/CNWs demonstrated good operational stability for up to eight successive esterification cycles to synthesize eugenyl benzoate.

Heterogeneous nuclear ribonucleoprotein K (hnRNP-K) promotes tumor metastasis by induction of genes involved in extracellular matrix, cell movement, and angiogenesis.

Cancer is a leading cause of death and still awaits effective therapies. Rapid industrialization has contributed to increase in incidence of cancer. One of the reasons why most of the cancers fail therapy is due to their metastatic property. Hence identification of factors leading to metastasis is highly important to design effective and novel anti-cancer therapeutics. In our earlier study (Inoue, A., Sawata, S. Y., Taira, K., and Wadhwa, R. (2007) Loss-of-function screening by randomized intracellular antibodies: identification of hnRNP-K as a potential target for metastasis. Proc. Natl. Acad. Sci. U.S.A. 104, 8983-8988), we had reported that the involvement of heterogeneous nuclear ribonucleoprotein K (hnRNP-K) in metastasis. Here, we established hnRNP-K-overexpressing and -underexpressing derivative cell lines and examined their proliferation and metastatic properties in vitro and in vivo. Whereas hnRNP-K compromised cells showed delayed tumor growth, its overexpression resulted in enhanced malignancy and metastasis. Molecular basis of the hnRNP-K induced malignant and metastatic phenotypes was dissected by cDNA microarray and pathway analyses. We found that the hnRNP-K regulates extracellular matrix, cell motility, and angiogenesis pathways. Involvement of the selected genes (Cck, Mmp-3, Ptgs2, and Ctgf) and pathways was validated by gene-specific expression analysis. Our results demonstrated that the hnRNP-K is a potential target for metastasis therapy.

Oral and intranasal immunization with food-grade recombinant Lactococcus lactis expressing high conserved region of SARS-CoV-2 spike protein triggers mice's immunity responses.

The COVID-19 pandemic began at the end of 2019 in Wuhan, China, and has spread throughout the world. Vaccination is still the most effective method of prevention of pathogenic infections, including viral infections. However, there is little evidence that vaccination can protect against SARS-CoV-2 virus for a long time. Thus, regular re-vaccination is necessary to control COVID-19. Vaccination by injection is invasive, and is one of the reasons people refuse to get re-vaccinated. Therefore, we developed a less invasive vaccine based on oral or nasal administration. The gene encoding the high conserved region (HCR) spike protein was inserted into pNZ8149 and expressed in L.lactis NZ3900. Mice were immunized at 3-week intervals with oral or nasal routes. Anti-SARS-CoV2 spike antibody (IgG and IgA) level were measured using ELISA method before and after treatment. Plasma cells population in lymph were analyzed using flowcytometry and the CD4 + and CD8 + cells in lymph and intestine were analyzed using immunofluorescence method. The results of nasal and oral administration in experimental animals showed that L.lactis carrying the HCR gene could induce a humoral immune response, as indicated by increased levels of IgG and IgA against SARS-CoV-2 (IgG/IgA-SARS-CoV-2). The plasma cell population after nasal and oral vaccination in mice were significantly different with control group (p < 0.05). The CD4 + and CD8 + cells in intestine were significantly higher in orally immunized group mice than control group. The CD8 + cells in lymph were significantly higher in intranasal immunized group mice than control group. Our data demonstrate L.lactis expressing spike protein can be developed into a less invasive alternative to nasal and oral vaccination.

Understanding hypocholesterolemic activity of soy isoflavones: Completing the puzzle through computational simulations.

The hypocholesterolemic activity of soy isoflavones has been studied, but the exact mechanism underlying the activity remains unclear. This study reveals the proposed mechanism of the cholesterol-lowering effect of soy isoflavones by computational simulations. Daidzin, Glycitin, Genistin, Daidzein, Glycitein, Genistein, Glyceollin I, Glyceollin II, and Glyceollin III were selected to be analyzed their interaction with 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A Reductase (HMGCR) and Sterol Regulatory Element-Binding Protein 2 (SREBP2) as key factors in cholesterol biosynthesis as well as Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) as a common target for hypercholesterolemia. Protein-isoflavones interaction was analyzed using AutoDock. According to binding energy calculations, a total of five out of those nine isoflavones, including Glycitin, Genistin, Genistein, Glyceollin II, and Glyceollin III, were favored to be a HMGCR inhibitor but not with SREBP2 and PCSK9. Those isoflavones were then compared with Simvastatin as known inhibitor of HMGCR. Isoflavone with binding energy lower than Simvastatin then directed to molecular dynamics using YASARA and headed into toxicity estimations. Almost all of those isoflavones could bind with HMGCR with better stability than Simvastatin according to molecular dynamics simulations. Toxicity prediction filtered two out of the five isoflavones mentioned earlier as the proper candidate to be an HMGCR inhibitor. Those isoflavones were Genistin and Genistein. In summary, the hypocholesterolemic activity of soy isoflavones may occur by blocking the cholesterol biosynthesis pathway.Communicated by Ramaswamy H. Sarma.

Antioxidant and Anti-inflammatory Activity of Sea Cucumber (Holothuria scabra) Active Compounds against KEAP1 and iNOS Protein.

Oxidative stress and inflammation have a role in the development of various diseases. Oxidative stress and inflammation are associated with many proteins, including Kelch ECH associating protein 1 (KEAP1) and inducible nitric oxide synthase (iNOS) proteins. The active compounds contained in Holothuria scabra have antioxidant and anti-inflammatory properties. This study aimed to evaluate the antioxidant and anti-inflammatory activity of sea cucumber's active compounds by targeting KEAP1 and iNOS proteins. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) scavenging activity of H. scabra extract were measured spectrophotometrically. The 3-dimensional (3D) structures of sea cucumber's active compounds and proteins were obtained from the PubChem and Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) databases. Molecular docking was performed using AutoDock Vina software. Molecular dynamics simulations were carried out using Yet Another Scientific Artificial Reality Application (YASARA) software with environmental parameters according to the cell's physiological conditions. The membrane permeability test was performed using the PerMM web server. The methanol extract of H. scabra had a weak antioxidant activity against DPPH and strong activity against NO radical. Scabraside and holothurinoside G had the most negative binding affinity values when interacting with the active site of KEAP1 and iNOS proteins. Molecular dynamics simulations also showed that both compounds were stable when interacting with KEAP1 and iNOS. However, scabraside and holothurinoside G were difficult to penetrate the cell plasma membrane, which is seen from the high energy transfer value in the lipid acyl chain region of phospholipids. Scabraside and holothurinoside G are predicted to act as antioxidants and anti-inflammations, but in their implementation to in vitro and in vivo study, it is necessary to have liposomes or nanoparticles, or other delivery methods to help these 2 compounds enter the cell.

Pulsed Radiofrequency Decreases pERK and Affects Intracellular Ca2+ Influx, Cytosolic ATP Level, and Mitochondrial Membrane Potential in the Sensitized Dorsal Root Ganglion Neuron Induced by N-Methyl D-Aspartate.

Background: The molecular mechanism of pulsed radiofrequency (PRF) in chronic pain management is not fully understood. Chronic pain involves the activation of specific N-Methyl D-Aspartate receptors (NMDAR) to induce central sensitization. This study aims to determine the effect of PRF on central sensitization biomarker phosphorylated extracellular signal-regulated kinase (pERK), Ca2+ influx, cytosolic ATP level, and mitochondrial membrane potential (Δψm) of the sensitized dorsal root ganglion (DRG) neuron following NMDAR activation. Methods: This study is a true experimental in-vitro study on a sensitized DRG neuron induced with 80 µM NMDA. There are six treatment groups including control, NMDA 80 µM, Ketamine 100 µM, PRF 2Hz, NMDA 80 µM + PRF 2 Hz, and NMDA 80 µM + PRF 2 Hz + ketamine 100 µM. We use PRF 2 Hz 20 ms for 360 seconds. Statistical analysis was performed using the One-Way ANOVA and the Pearson correlation test with α=5%. Results: In the sensitized DRG neuron, there is a significant elevation of pERK. There is a strong correlation between Ca2+, cytosolic ATP level, and Δψm with pERK intensity (p<0.05). PRF treatment decreases pERK intensity from 108.48 ± 16.95 AU to 38.57 ± 5.20 AU (p<0.05). PRF exposure to sensitized neurons also exhibits a Ca2+ influx, but still lower than in the unexposed neuron. PRF exposure in sensitized neurons has a higher cytosolic ATP level (0.0458 ± 0.0010 mM) than in the unexposed sensitized neuron (0.0198 ± 0.0004 mM) (p<0.05). PRF also decreases Δψm in the sensitized neuron from 109.24 ± 6.43 AU to 33.21 ± 1.769 AU (p<0.05). Conclusion: PRF mechanisms related to DRG neuron sensitization are by decreasing pERK, altering Ca2+ influx, increasing cytosolic ATP level, and decreasing Δψm which is associated with neuron sensitization following NMDAR activation.

Sea Cucumber Compounds Targeting NF-κB in Cancer Treatment.

Cancer is a major health problem worldwide and the leading cause of death in many countries. It remains challenging to find anticancer treatments that work efficiently for varying types of cancer cells. Several studies revealed that nuclear factor kappa B (NF-κB) is a family of dimeric transcription factors that induce tumor promotion, progression, and therapeutic resistance, providing evidence that NF-kB may be a promising target for cancer drugs. Some research has found that sea cucumber biocompounds have anticancer properties, but further research is essential to confirm anticancer targets. This manuscript discusses the mechanisms of anticancer targeting the NF-κB signaling pathway induced by sea cucumber-derived compounds. Additional database analysis showed the protein targeted by the compounds involved in several pathways related to the NF-κB network. Moreover, SwissADME predicted druglikeliness properties of the active compounds of sea cucumber. The discussion is expected to provide new insight into the promising potential of these marine natural products for the treatment of many different types of cancers.

The combination of Elephantopus scaber and Phaleria macrocarpa leaves extract promotes anticancer activity via downregulation of ER-α, Nrf2 and PI3K/AKT/mTOR pathway.

BACKGROUND: Elephantopus scaber and Phaleria macrocarpa have recently been interested as novel anticancer agents. However, there was no scientific evaluation of the anticancer effect of both plant combinations. OBJECTIVE: This study investigated the potential anticancer effects of combined E. scaber and P. macrocarpa leaves extract on human breast cancer cells lines. MATERIALS AND METHODS: T47D cells were treated with the combination of E. scaber and each part of P. macrocarpa (leaves/EL, mesocarp/EM, seed/ES and pericarp/EP). T47D cells were then exposed to three ratios (1:1, 2:1, and 1:2) of the best combination for 24, 48, and 72 h. The cell viability of T47D and TIG-1 cells was assessed using WST-1 assay. The apoptotic hallmarks were determined using FITC Annexin V-PI staining and DNA fragmentation assay. The cell proliferation and cell cycle profiles were analyzed using CFSE (carboxyfluorescein succinimidyl ester) and Propidium iodide-flowcytometry assays. The relative number of p-ERα, p-Nrf2, p-PI3K, p-AKT, and p-mTOR were assessed using flow cytometry. The molecular docking analysis was also performed to confirm the mechanism of the extract in silico. RESULTS: The combination of E. scaber and P. macrocarpa leaves (EL) possessed strong cytotoxic activity (p < 0.05) than other combination groups and cisplatin. EL showed selective killing only to T47D cells. EL at a ratio of 2:1 potentially suppressed the cell viability and cell division, induced apoptosis, and arrested the cell cycle of T47D cells by triple inhibiting the p-Nrf2, p-ERα, and p-PI3K/AKT/mTOR signaling pathway. Molecular docking analysis confirmed that the possible mechanism of EL to reduce T47D cell growth was by inhibiting ERα and Nrf2-complex, resulting in the reduction in the crosstalk effect of Nrf2, ERα and PI3K/AKT/mTOR pathways. CONCLUSION: The combination of leaf extracts from E. scaber and P. macrocarpa caused cell death in breast cancer cells T47D and not in normal cells TIG-1; hence has the potential to show anticancer efficacy in preclinical and clinical trials.

Serine racemase interaction with N-methyl-D-aspartate receptors antagonist reveals potential alternative target of chronic pain treatment: Molecular docking study.

Serine racemase (SR) catalyzes L-serine racemization to activate the N-methyl-D-aspartate receptor (NMDAR). NMDAR activation is associated with the progression of acute-to-chronic neuropathic pain. This study aimed to investigate NMDAR antagonist interactions with SR to obtain potential chronic pain target therapy. Several NMDAR antagonist drugs were obtained from the drug bank, and malonate was used as a control inhibitor. Ligands were prepared using the open babel feature on PyRx. The SR structure was obtained from Protein data bank (PDB) (3l6B) and then docked with ligands using the AutoDock Vina. Haloperidol had a lower binding affinity than malonate and other ligands. Ethanol had the highest binding affinity than other drugs but could bind to the Adenosine triphosphate (ATP)-binding domain. Haloperidol is bound to reface that function for reprotonation in racemization reaction to produce D-serine. Halothane bond with Arg135 residues aligned negatively charged substrates to be reprotonated properly by reface. Tramadol is bound to amino acid residues in the triple serine loop, which determines the direction of the SR reaction. Several NMDAR antagonists such as haloperidol, halothane, ethanol, and tramadol bind to SR in the specific binding site. It reveals that SR potentially becomes an alternative target for chronic pain treatment.

Metabarcoding dataset on the elicitation of Soybean and Mungbean using Ragi Tape as elicitors for enhancing secondary metabolites production.

Ragi Tape (RT) is commonly used as the microbial starter for various Indonesian traditional food. Consist of diverse microbial populations, RT has excellent agents as elicitors to augment the bioactive compounds in Soybean (SB) and Mungbean (MB). Metabarcoding analysis has shown to identify the microbial population involved in elicitation using RT. Inoculated RT from SB and MB were collected to extract the microbial DNA for the post-elicitation group. In comparison, DNA extraction from powdered RT was conducted as a pre-elicitation group. The total DNA were then sequenced by using the MiSeq Illumina platform with 16S rDNA gene region V3-V4 and 18S rDNA gene region V4 as a biomarker for bacterial and fungal identification, correspondingly. The obtained raw-data sequences were then analyzed using QIIME2 pipeline. According to the number of the acquired sequences, the 18S sequencing yielded more DNA strands than the 16S sequencing. However, the number of assigned OTUs was higher in 16S sequences than 18S sequences. From the perspective of the sample, RT has larger distinctive taxa, which were not identified in other samples. This metagenome data will provide fundamental information on RT employment in the elicitation process and further understanding of elicitation mechanisms using RT as biotic elicitors. The data is available at the BioProject database under the NCBI domain with accession no. PRJNA767401.

Lactobacillus plantarum FNCC 0137 fermented red Moringa oleifera exhibits protective effects in mice challenged with Salmonella typhi via TLR3/TLR4 inhibition and down-regulation of proinflammatory cytokines.

BACKGROUND: Salmonella typhi is a foodborne pathogenic bacterium that threatens health. S. typhi infection exacerbated the antibiotic resistance problem that needs alternative strategies. Moringa oleifera possesses anti-inflammatory and antimicrobial effects. However, there is a lack of information about the pharmacological value of red M. oleifera. The fermentation of red M. oleifera leaves extract (RMOL) is expected to add to its nutritional value. OBJECTIVE: The present study aimed to evaluate non-fermented RMOL (NRMOL) and fermented RMOL (FRMOL) effects on S. typhi infection in mice. MATERIALS AND METHODS: Female Balb/C mice were randomly divided into eight groups. The treatment groups were orally administered with NRMOL or FRMOL at doses 14, 42, and 84 mg/kg BW during the 28 days experimental period. Then S. typhi was introduced to mice through intraperitoneal injection except in the healthy groups. The NRMOL or FRMOL administration was continued for the next seven days. Cells that expressed CD11b+ TLR3+, CD11b+TLR4+, CD11b+IL-6+, CD11b+IL-17+, CD11b+TNF-a+, and CD4+CD25+CD62L+ were assessed by flow cytometry. RESULTS: Our result suggested that NRMOL and FRMOL extracts significantly reduced (p <0.05) the expression of CD11b+TLR3+, CD11b+TLR4+, CD11b+IL-6+, CD11b+IL-17+, and CD11b+TNF-α+ subsets. In contrast, NRMOL and FRMOL extracts significantly increased (p <0.05) the expression of CD4+CD25+CD62L+ subsets. NRMOL at dose 14 and 42 mg/kg BW was more effective compared to FRMOL in reducing the expression of CD11b+TLR3+, CD11b+TLR4+, and CD11b+TNF-α+ subsets. CONCLUSION: Our findings demonstrated that NRMOL and FRMOL extracts could be promising agents for protection against S. typhi infection via modulation of TLR3/TLR4, regulatory T cells, and proinflammatory cytokines.

Anticancer activity of Caesalpinia sappan by downregulating mitochondrial genes in A549 lung cancer cell line.

Background: The standardization and mechanism of action of  Caesalpinia sappan as an anticancer agent are still lacking. This study aimed to understand the mechanism of action of  C,sappan extract as an anticancer agent. Methods: This study was conducted using the A549 lung cancer cell line to understand the mechanism of action of  C. sappan extract as an anticancer agent. The cytotoxicity activity, cell cycle progression, apoptosis, protein-related apoptosis (i.e., BCL-2and BAX protein) assays, and RNA sequencing were performed level were measured. Moreover, the antioxidant activity, total flavonoids, and phenolics of C.sappan were also assessed. Results: C.sappan has strong antioxidant activity (22.14 ± 0.93 ppm) total flavonoid content of (529.3 ± 4.56 mgQE/g), and phenolics content of (923.37 ± 5 mgGAE/g). The C.sappan ethanol extract inhibited cancer cell growth and arrested at G0/G1 phase of cell cycle, inducing apoptosis by increasing BAX/BCL-2 protein ratio in A549 lung cancer cell line. Furthermore, results from RNA sequencing analysis showed that C.sappan ethanol extract caused downregulation of genes acting on mitochondrial function including adenosine triphosphate (ATP) production and respiration. Conclusions: This study demonstrated that C.sappan has the ability to inhibit cancer cell growth by inducing apoptosis and mitochondrial dysfunction in A549 cells.

A Potential Anticancer Mechanism of Finger Root (Boesenbergia rotunda) Extracts against a Breast Cancer Cell Line.

Breast cancer is the most common type of cancer women suffer from worldwide in 2020 and the 4th leading cause of cancer death. Boesenbergia rotunda is an herb with high potential as an anticancer agent. This study explores the potential bioactive compounds in B. rotunda as anti-breast cancer agents using in silico and in vitro approaches. The in silico study was used for active compound analysis, selection of anticancer compound candidates, prediction of target protein, functional annotation, molecular docking, and molecular dynamics simulation, respectively. The in vitro study was conducted by measurement toxicity, rhodamine 123, and apoptosis assays on T47D cells. Based on the KNApSAcK database, B. rotunda contained 20 metabolites, which are dominated by chalcone and flavonoid groups. Seven of them were predicted to have anticancer activity, namely, sakuranetin, cardamonin, alpinetin, 2S-pinocembrin, 7.4'-dihydroxy-5-methoxyflavanone, 5.6-dehydrokawain, and pinostrobin chalcone. These compounds targeted proteins related to cancer progression pathways such as the PI3K/Akt, FOXO, JAK/STAT, and estrogen signaling pathways. Therefore, these compounds are predicted to inhibit growth and induce apoptosis of cancer cells through their interactions with MMP12, MMP13, CDK4, JAK3, VEGFR1, VEGFR2, and KCNA3. Anticancer activity of B. rotunda through in vitro study confirmed that B. rotunda extract is strong cytotoxic and induces apoptosis of breast cancer cell lines. This study concludes that Boesenbergia rotunda has potency as an anticancer candidate.

miR-155-5p predictive role to decelerate foam cell atherosclerosis through CD36, VAV3, and SOCS1 pathway.

MicroRNAs (miRNAs) are noncoding RNA molecules that play a significant role in atherosclerosis pathogenesis through post-transcriptional regulation. In the present work, a bioinformatic analysis using TargetScan and miRdB databases was performed to identify the miRNAs targeting three genes involved in foam cell atherosclerosis (CD36, Vav3, and SOCS1). A total number of three hundred and sixty-seven miRNAs were recognized and only miR-155-5p was selected for further evaluation based on Venn analysis. Another objective of this study was to evaluate the biological process and regulatory network of miR-155-5p associated with foam cell atherosclerosis using DIANA, DAVID, Cytoscape, and STRING tools. Additionally, the comprehensive literature review was performed to prove the miR-155-5p function in foam cell atherosclerosis. miR-155-5p might be related with ox-LDL uptake and endocytosis in macrophage cell by targeting CD36 and Vav3 genes which was showed from the KEGG pathways hsa04979, hsa04666, hsa04145 H, hsa04810, and GO:0099632, GO:0060100, GO:0010743, GO:001745. Furthermore, miR-155-5p was also predicted to increase the cholesterol efflux from macrophage by inhibit SOCS1 expression based on KEGG pathway hsa04120. Eleven original studies were included in the review and strongly suggest the role of miR-155-5p in foam cell atherosclerosis inhibition.

Bioinformatics Study of Sea Cucumber Peptides as Antibreast Cancer Through Inhibiting the Activity of Overexpressed Protein (EGFR, PI3K, AKT1, and CDK4).

Breast cancer is the most common type of cancer in women globally. The overexpressed proteins, including EGFR, PI3K, AKT1, and CDK4, have a role in the growth of breast cancer cells. The 3D peptide structure of sea cucumber Cucumaria frondosa was modeled and then docked with EGFR, PI3K, AKT1, and CDK4 proteins using AutoDock Vina software. The docking result, which has the best binding affinity value, is continued with molecular dynamics simulation. The docking results showed that all peptides bind to the active sites of the four proteins. WPPNYQW and YDWRF peptides bind to proteins with lower binding affinity values than positive controls. The four proteins were in a stable state when complexed with the WPPNYQW peptide, which was seen from the RMSD and RMSF value. PI3K-YDWRF and AKT1-YDWRF complexes are stable, characterized by high RMSD values and increased volatility in several amino acids. WPPNYQW peptide has high potential as an antibreast cancer agent because it binds to the active sites of the four proteins with low binding affinity values and stable interactions. Meanwhile, the YDWRF peptide interacts with the four proteins with low binding affinity values, but the interaction is only stable on PI3K and AKT1 proteins.

Cardiovascular protection effect of chlorogenic acid: focus on the molecular mechanism.

Vascular endothelial cells have a variety of functions such as the control of blood coagulation, vascular permeability, and tone regulation, as well as quiesce of immune cells. Endothelial dysfunction is a cardiovascular events predictor, which is considered the initial stage in atherosclerosis development. It is characterized by alterations in endothelium functions due to imbalanced vasodilators and vasoconstrictors, procoagulant and anticoagulant mediators, as well as growth inhibitor and promotor substances. Chlorogenic acid (CGA) is the primary polyphenol in coffee and some fruits. It has many health-promoting properties, especially in the cardiovascular system. Many studies investigated the efficacy and mechanism of this compound in vascular health. CGA has several vascular benefits such as anti-atherosclerosis, anti-thrombosis, and anti-hypertensive. This review focuses on the molecular mechanism of CGA in vascular health.

Beneficial effects of green coffee and green tea extract combination on metabolic syndrome improvement by affecting AMPK and PPAR-α gene expression.

Effect of green coffee and green tea extract on metabolic syndrome. To explore green coffee and green tea extract combination effect on metabolic profile and blood pressure improvement through adenosine monophosphate-activated protein kinase (AMPK) and Peroxisome Proliferator-Activated Receptor α (PPARα) gene expression modulation. Experimental laboratory research with pre- and post-control group design. Twenty-five metabolic syndrome rats model were grouped into five groups (n = 5): standard control (normal), metabolic syndrome (SM), green coffee extract (GC), green tea extract (GT), and combination green coffee and green tea extract (CM). The extract was given during 9 weeks. Serum glucose, triglyceride, high-density lipoprotein, and systolic blood pressure level were analyzed before and after the extract administration. At the end of the study, PPAR-α and AMPK-α2 gene were analyzed. Independent t-test. CM group had significantly higher PPAR-α, and AMPK-α2 gene expression compared to those of SM, GC, and GT group. Green coffee and green tea extract combination administration improved metabolic profile and blood pressure on metabolic syndrome through affecting PPAR-α and AMPK-α2 gene expression.

CARF: an emerging regulator of p53 tumor suppressor and senescence pathway.

Replicative senescence, a major outcome of normal cells with finite lifespan, is a widely accepted in vitro model for ageing studies. Limited repair and defense mechanisms of normal cells, in addition to DNA alterations and oncogene inductions under stress, are believed to result in senescence as a protective mechanism to prevent undesirable proliferation of cells. The ARF/p53/p21(cip1/waf1) tumor suppression pathway acts as a molecular sensor and regulator of cellular stress, senescence, and immortalization. Understanding the molecular regulation of this pathway by intrinsic and extrinsic signals is extremely important to address unsolved questions in senescence and cancer. CARF was first discovered as a binding partner of ARF and has since been shown to have both ARF-dependent and -independent functions that converge to regulate p53 pathway. CARF directly binds to p53 and HDM2, and functions in a negative feedback pathway. Whereas CARF transcriptionally represses HDM2 to increase p53 activity, HDM2 in return degrades CARF. Thus, CARF may act as a novel key regulator of the p53 pathway at multiple checkpoints. The aim of this article is to discuss the current knowledge about functions of CARF and its impact on p53 pathway in regulation of senescence and carcinogenesis.

Merger of ayurveda and tissue culture-based functional genomics: inspirations from systems biology.

Ayurveda is one of the ancient systems of health care of Indian origin. Roughly translated into "Knowledge of life", it is based on the use of natural herbs and herb products for therapeutic measures to boost physical, mental, social and spiritual harmony and improve quality of life. Although sheltered with long history and high trust, ayurveda principles have not entered laboratories and only a handful of studies have identified pure components and molecular pathways for its life-enhancing effects. In the post-genomic era, genome-wide functional screenings for targets for diseases is the most recent and practical approach. We illustrate here the merger of ayurveda and functional genomics in a systems biology scenario that reveals the pathway analysis of crude and active components and inspire ayurveda practice for health benefits, disease prevention and therapeutics.