835 research outputs found
Moringin, an isothiocyanate improves the susceptibility of breast cancer cells to doxorubicin
Background: Breast cancer has become the most frequent tumor worldwide and is expected to have a large impact on cancer fatalities globally. Thus, the development of precise molecular diagnosis and prognosis is essential for the effective treatment of breast cancer patients. Doxorubicin (DOXO) is the widely accepted chemotherapeutic drug for the treatment of breast cancer. However, the primary challenge with current chemotherapy drugs is their toxic effects on healthy tissues. Moringin (MG), an Isothiocyanate (ITC) is produced from the seeds of Moringa oleifera. It is produced from the myrosinase-catalyzed hydrolysis of glucomoringin. Chemosensitization is a strategy used in cancer treatment to make cancerous cells more responsive to chemotherapeutic drugs. A chemosensitizing drug is used in therapy to reduce the doses of potential anticancer drugs, tackle the resistance of cancer cells to these treatments, prevent healthy cells from toxicity, and decrease side effects for patients. In this study, we investigated the potential of MG alone and in conjunction with DOXO against breast cancer cells.
Methods: MCF-7 and MDA-MB-231 breast cancer cell lines were used in the investigation. The chemo-sensitization experiments of MG, both alone and in combination with DOXO, were investigated by using the MTT and colony formation assay. Apoptosis was examined by using the AO/PI dual staining, cell cycle analysis, and mitochondrial membrane potential measurement. Expression of cell survival proteins was assessed through semi-quantitative PCR and western blotting. Expression of long non-coding RNAs was performed by qRT-PCR.
Results: The MTT and clonogenic assay results revealed the anti-proliferative potential of MG both alone and in combination of DOXO. The expression of proteins involved in cell survival (PARP, Bcl-2, Bcl-xL and Survivin) is also downregulated in combination compared to individual drug. We observed an increase in the sub-G1 and S-phase population in MG and DOXO (both individual as well in combination). However, the G1 and G2/M population was slightly decreased with MG and DOXO (both individual as well in combination). The expression of oncogenic lncRNAs such as H19, HOTAIR and NKILA, were reduced and the expression of tumor suppressor genes such as MEG3, GAS5 and MALAT1 was increased.
Conclusions: Taken together, results of this study provide evidence that, MG in breast cancer cell lines increases the susceptibility of breast cancer cells to DOXO
Epoxyazadiradione exhibit antiâcancer activities by modulating lncRNAs expression in pancreatic cancer
Background: Azadirachta indica (neem), a medicinal plant under Meliaceae family, is found in the Indian subcontinent. One of the limonoids, epoxyazadiradione (EPA), is a phytochemical isolated from the seeds of this tree. This is widely used in traditional medicine to treat a variety of human ailments. Although EPA has shown promise against some cancer types, its efficacy against pancreatic cancer and the underlying mechanism remains elusive.
Aim: We examined the antiâcancer activity of EPA against pancreatic cancer cells. We also examined the underlying mechanism.
Methods: Pancreatic cancer cell lines (PANC-1 and MiaPaCa-2) were used during the study. We performed MTT assay, clonogenic colony formation assay for cytotoxicity. The western blotting was performed to examine the expression pattern of various apoptotic proteins. Real-time PCR was performed to detect quantitative lncRNAs expression.
Results and Discussion: After treatment with EPA, the viability and proliferation of pancreatic cancer cells was decreased in a dose- and time-dependent manner. EPA suppressed the expression of apoptotic proteins involved in survival, proliferation, migration and invasion. EPA also suppressed the expression of MMP-9 in a concentration-dependent manner in pancreatic cancer cells. In addition, the limonoid also modulated the expression of lncRNAs (MEG-3, GAS-5, H19 and MHRT).
Conclusion: EPA exhibited strong anti-cancer activities against pancreatic cancer by modulating multiple cancer-related signalling molecules
Metabolic reprogramming in breast cancer patients as revealed by 1H NMR spectroscopy
Background: Breast cancer is a global health concern among women. Several metabolic pathways are dysregulated in breast cancer cells, including alterations in energy metabolism, amino acid metabolism, and lipid metabolism. Reprogramming of metabolic pathways may facilitate inappropriate proliferation of cancer cells and adaptation to the tumor microenvironment. Long non-coding RNAs (lncRNAs) have emerged as important regulatory targets in the process of tumorigenesis. However, the role of lncRNAs in the process of metabolic reprogramming is not properly known. Exploring metabolic alterations and its association with lncRNAs expression might be helpful for developing new biomarkers and therapeutic targets for cancer management.
Objectives: Serum from 43 breast cancer patients and 13 healthy individuals were used for the analysis of metabolic profile.
Methods: For the identification and quantification of metabolites, 1H NMR spectroscopy was used while for lncRNAs expression, q-RT-PCR was used.
Results: Metabolites such as amino acids, lipids, membrane metabolites, lipoproteins, and energy metabolites were observed in the serum of both patients and healthy individuals. The serum of patients and healthy individuals produced measurable amounts of metabolites related to lipoproteins, amino acids, membrane, lipids, and energy. The unsupervised PCA, supervised PLS-DA, supervised OPLS-DA, and random forest classification analyses revealed alterations in more than 25 metabolites. Further analysis of metabolites with AUC value \u3e0.9 revealed significant elevation in the levels of LPR, glycerol, and lactate, while the levels of succinate, glucose, and isobutyrate was reduced in comparison to healthy control. The advanced stage breast cancer patients revealed alterations in these metabolites (except LPR) in comparison to early breast cancer patients. Over 25 metabolic signaling pathways were associated with altered metabolites. Further, a dysregulation in MEG3, H19, and GAS5 lncRNAs were observed in the breast tumor tissue in comparison to normal adjacent tissue.
Conclusion: The study reveals that metabolic pathways are altered in breast cancer patients. The study also opens a window for examining the association of lncRNAs with metabolic patterns in patients
Molecular basis for the pharmacological activities of piperlongumine against breast cancer: Role of glucose import, ROS, NF-ÎșB and lncRNAs
Background: Piperlongumine (PL, piplartine) is an alkaloid derived from the Piper longum L. (long pepper) root. The activities PL against breast cancer and the underlying mechanism is not thoroughly investigated.
Aim: We examined the anti-cancer activities of PL against breast cancer cells. The molecular basis for the pharmacological activities of this alkaloid was also examined.
Methods: The breast cancer cell lines such as MCF-7, T-47D, MDA-MB-231, MDA-MB-468 and MDA-MB-453 were used during the study. We used MTT assay, clonogenic and soft agar colony formation assay for cytotoxicity. The cell cycle analysis, phosphatidylserine externalization assay, measurement of mitochondrial membrane potential, AO/PI and DAPI staining, and DNA laddering was used for apoptosis. The western blot analysis was performed to examine the expression pattern of tumorigenic proteins. Other parameters used were the intracellular detection of ROS, immunocytochemistry for NF-ÎșB and GLUT-1 activation, wound healing assay for cell migration, and real-time PCR for lncRNA expression. We also evaluated if PL can enhance the efficacy of doxorubicin in swiss albino mice implanted with Ehrlich Ascites Carcinoma (EAC) cells and metabolic parameters were also examined in serum of mice.
Results: PL inhibited proliferation and suppressed the long-term as well as soft agar colony formation of breast cancer cells in a dose dependent manner. PL induced ROS generation and accumulation of cells in sub-G1 phase, mitochondria mediated apoptosis in cancer cells as revealed by the presence of fragmented nuclei, PARP activation, loss of mitochondrial membrane potential, chromatin condensation, DNA laddering and suppression in the expression of cell survival proteins. PL reduced glucose import and modifies the expression of glucose and lactate transporter in breast cancer cells. The amide alkaloid suppresses the TNF-α induced NF-ÎșB activation and modulate the lncRNAs such as MEG-3, GAS-5 and H19 expression in breast cancer. In mice model, PL was found to synergize with doxorubicin by reducing the size, volume and weight of the tumor. With an increase in the concentration of PL, the serum cholesterol and triglyceride levels were decreased while there was increase in the serum level of glucose in EAC bearing mice.
Conclusion: PL exhibit potential against breast cancer. Further, PL enhances the efficacy of doxorubicin in EAC mice model. The modulation of lncRNAs, NF-ÎșB and glucose import may contribute to the activities of PL against breast cancer
Inflammation, a Double-Edge Sword for Cancer and Other Age-Related Diseases
Increasing evidence from diverse sources during the past several years has indicated that long-term, low level, chronic inflammation mediates several chronic diseases including cancer, arthritis, obesity, diabetes, cardiovascular diseases, and neurological diseases. The inflammatory molecules and transcription factors, adhesion molecules, AP-1, chemokines, C-reactive protein (CRP), cyclooxygenase (COX)-2, interleukins (ILs), 5-lipooxygenase (5-LOX), matrix metalloproteinases (MMPs), nuclear factor (NF)-kB, signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor (TNF), and vascular endothelial growth factor (VEGF) are molecular links between inflammation and chronic diseases. Thus, suppression of inflammatory molecules could be potential strategy for the prevention and therapy of chronic diseases. The currently available drugs against chronic diseases are highly expensive, minimally effective and produce several side effects when taken for long period of time. The focus of this review is to discuss the potential of nutraceuticals derived from âMother Natureâ such as apigenin, catechins, curcumin, ellagic acid, emodin, epigallocatechin gallate, escin, fisetin, flavopiridol, genistein, isoliquiritigenin, kaempferol, mangostin, morin, myricetin, naringenin, resveratrol, silymarin, vitexin, and xanthohumol in suppression of these inflammatory pathways. Thus, these nutraceuticals offer potential in preventing or delaying the onset of chronic diseases. We provide evidence for the potential of these nutraceuticals from pre-clinical and clinical studies
Mechanochemical synthesis of a new triptycene-based imine-linked covalent organic polymer for degradation of organic dye
In the present work, a novel triptycene-based imine-linked covalent organic polymer (TP-COP) was designed and synthesized via room-temperature, solvent-free mechanochemical grinding. The as-synthesized TP-COP material was fully characterized by Fourier transform infrared spectroscopy, solid-state NMR, field emission scanning electron microscopy (FESEM), high-resolution transmission electron microscopy (HRTEM), Brunauer-Emmett-Teller method, thermogravimetric analysis, diffuse reflectance spectroscopy (DRS), and electron paramagnetic resonance (EPR). The HRTEM image of TP-COP clearly indicates the presence of graphene-like layered morphology (exfoliated layers). The DRS study reveals that TP-COP exhibited a low optical band gap value of 2.49 eV, implying its semiconducting nature. Further, the EPR study confirmed the semiconducting behavior of TP-COP through the generation of free radicals. These findings suggest that TP-COP could be used as an efficient photocatayst for the degradation of organic dye (RhB) under solar irradiation. Moreover, TP-COP showed excellent reusability in degrading dye (RhB) without obvious performance decay
Mechanochemical synthesis of a new triptycene-based imine-linked covalent organic polymer for degradation of organic dye
In the present work, a novel triptycene-based imine-linked covalent organic polymer (TP-COP) was designed and synthesized via room-temperature, solvent-free mechanochemical grinding. The as-synthesized TP-COP material was fully characterized by Fourier transform infrared spectroscopy, solid-state NMR, field emission scanning electron microscopy (FESEM), high-resolution transmission electron microscopy (HRTEM), Brunauer-Emmett-Teller method, thermogravimetric analysis, diffuse reflectance spectroscopy (DRS), and electron paramagnetic resonance (EPR). The HRTEM image of TP-COP clearly indicates the presence of graphene-like layered morphology (exfoliated layers). The DRS study reveals that TP-COP exhibited a low optical band gap value of 2.49 eV, implying its semiconducting nature. Further, the EPR study confirmed the semiconducting behavior of TP-COP through the generation of free radicals. These findings suggest that TP-COP could be used as an efficient photocatayst for the degradation of organic dye (RhB) under solar irradiation. Moreover, TP-COP showed excellent reusability in degrading dye (RhB) without obvious performance decay
The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis
Background: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. Methods: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. Results and Conclusion: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events
MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV
Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe
Measurement of prompt open-charm production cross sections in proton-proton collisions at root s=13 TeV
The production cross sections for prompt open-charm mesons in proton-proton collisions at a center-of-mass energy of 13TeV are reported. The measurement is performed using a data sample collected by the CMS experiment corresponding to an integrated luminosity of 29 nb(-1). The differential production cross sections of the D*(+/-), D-+/-, and D-0 ((D) over bar (0)) mesons are presented in ranges of transverse momentum and pseudorapidity 4 < p(T) < 100 GeV and vertical bar eta vertical bar < 2.1, respectively. The results are compared to several theoretical calculations and to previous measurements.Peer reviewe
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