Epoxyazadiradione exhibit anti‑cancer 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 anti‑cancer 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

Molecular basis for the pharmacological activities of piperlongumine against breast cancer: Role of glucose import, ROS, NF-κB 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-κB 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-κB 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-κB 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 “Mother Nature” 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

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV