Curcumin inhibits NF-kB and Wnt/β-catenin pathways in cervical cancer cells

Curcumin is a natural non-toxic phenol which is isolated from Curcumin longa L. Mounting evidence has revealed the anticancer properties of curcumin in various tumors, but the underlying molecular mechanisms of this suppression in cervical cancer is still remained unclear. Here we assessed the antitumor effects of curcumin compared with 5-Fluorouracil in Hella cells in spheroids models and monolayer cell cultures. The anti-proliferative effects of curcumin and 5-Fluorouracil were as examined in spheroid and monolayer models. The expression levels of Wnt/β-catenin and NF-kB pathways as well as the influence of the cell cycle were evaluated. Curcumin inhibited cell growth in Hella cells through the regulation of NF-kB and Wnt pathways. Also, cells developed a G2/M cell cycle arrest followed by sub-G1 apoptosis with 5-Fluorouracil and curcumin. It was also shown that curcumin either considerably affects the Wnt/β-catenin and NF-kB pathways. We showed that curcumin inhibits invasion and proliferation of cervical cancer cells via impairment of NF-kB and Wnt/β-catenin pathways, proposing further studies on the potential impacts of this compound on cancer therapy. © 2019 Elsevier Gmb

Therapeutic potentials of curcumin in the treatment of glioblstoma

Glioblastoma multiforme (GBM), a greatly aggressive malignancy of the brain, is correlated with a poor prognosis and low rate of survival. Up to now, chemotherapy and radiation therapy after surgical approaches have been the treatments increasing the survival rates. The low efficacy of mentioned therapies as well as their side-effects has forced researchers to explore an appropriate alternative or complementary treatment for glioblastoma. In experimental models, it has been shown that curcumin has therapeutic potentials to fight against GBM. Given that curcumin has pharmacological effects against cancer stem cells, as major causes of resistance to therapy in glioblastoma cells. Moreover, it has been showed that curcumin exerts its therapeutic effects on GBM cells via affecting on apoptosis, oxidant system, and inflammatory pathways. Curcumin would possess a synergistic impact with chemotherapeutic agents. Herein, we summarized the current findings on curcumin as therapeutic agent in the treatment of GBM. © 2020 Elsevier Masson SA

Quercetin and cancer: New insights into its therapeutic effects on ovarian cancer cells

Ovarian cancer is known as a serious malignancy that affects women's reproductive tract and can considerably threat their health. A wide range of molecular mechanisms and genetic modifications have been involved in ovarian cancer pathogenesis making it difficult to develop effective therapeutic platforms. Hence, discovery and developing new therapeutic approaches are required. Medicinal plants, as a new source of drugs, could potentially be used alone or in combination with other medicines in the treatment of various cancers such as ovarian cancer. Among various natural compounds, quercetin has shown great anti-cancer and anti-inflammatory properties. In vitro and in vivo experiments have revealed that quercetin possesses a cytotoxic impact on ovarian cancer cells. Despite obtaining good results both in vitro and in vivo, few clinical studies have assessed the anti-cancer effects of quercetin particularly in the ovarian cancer. Therefore, it seems that further clinical studies may introduce quercetin as therapeutic agent alone or in combination with other chemotherapy drugs to the clinical setting. Here, we not only summarize the anti-cancer effects of quercetin but also highlight the therapeutic effects of quercetin in the ovarian cancer. © 2020 The Author(s)

Design, modeling, expression, and chemoselective PEGylation of a new nanosize cysteine analog of erythropoietin

Reza Ahangari Cohan1, Armin Madadkar-Sobhani2,3, Hossein Khanahmad1, Farzin Roohvand4, Mohammad Reza Aghasadeghi4, Mohammad Hossein Hedayati5, Zahra Barghi5, Mehdi Shafiee Ardestani4, Davoud Nouri Inanlou1, Dariush Norouzian11Research and Development Department, Production and Research Complex, Pasteur Institute of Iran, Tehran, Iran; 2Department of Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran; 3Department of Life Sciences, Barcelona Supercomputing Center, Barcelona, Spain; 4Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran, Iran; 5Quality Control Department, Production and Research Complex, Pasteur Institute of Iran, Tehran, IranBackground: Recombinant human erythropoietin (rhEPO) is considered to be one of the most pivotal pharmaceutical drugs in the market because of its clinical application in the treatment of anemia-associated disorders worldwide. However, like other therapeutic proteins, it does not have suitable pharmacokinetic properties for it to be administrated at least two to three times per week. Chemoselective cysteine PEGylation, employing molecular dynamics and graphics in in silico studies, can be considered to overcome such a problem.Methods: A special kind of EPO analog was elicited based on a literature review, homology modeling, molecular dynamic simulation, and factors affecting the PEGylation reaction. Then, cDNA of the selected analog was generated by site-directed mutagenesis and subsequently cloned into the expression vector. The construct was transfected to Chinese hamster ovary/dhfr- cells, and highly expressed clones were selected via methotrexate amplification. Ion-immobilized affinity and size exclusion (SE) chromatography techniques were used to purify the expressed analog. Thereafter, chemoselective PEGylation was performed and a nanosize PEGylated EPO was obtained through dialysis. The in vitro biologic assay and in vivo pharmacokinetic parameters were studied. Finally, E31C analog Fourier transform infrared, analytical SE-high-performance liquid chromatography, zeta potential, and size before and after PEGylation were characterized.Results: The findings indicate that a novel nanosize EPO31-PEG has a five-fold longer terminal half-life in rats with similar biologic activity compared with unmodified rhEPO in proliferation cell assay. The results also show that EPO31-PEG size and charge versus unmodified protein was increased in a nanospectrum, and this may be one criterion of EPO biologic potency enhancement.Discussion: This kind of novel engineered nanosize PEGylated EPO has remarkable advantages over rhEPO.Keywords: nanoPEGylated EPO, cysteine PEGylation, pharmacokinetic propert

Meta-analysis: COVID-19 diagnosis in chest CT�master key for radiologists

Background: COVID-19 was discovered in February in China. Due to the high prevalence of the disease, early detection and rapid isolation of patients are the vital points for controlling the outbreak. The purpose of this study was to determine the correct location of chest CT scan in the diagnosis of COVID-19. Main text: The current study is a systematic review and meta-analysis. 2959 papers were found in all national and international databases. The study has been reported based on the PRISMA checklist. All analyses were done by CMA Ver. 2 software. The statistical analysis results show that the GGO observation level in the available shape was 46 in CT scan results, and the consolidation observation level in the general form was 33 in CT scan results. Pleural effusion was 7, and linear opacity observation level was 24 in CT scan results in the general form. The CT scan test sensitivity level was gained 94.7, and PCR test sensitivity level was achieved as 94.8. This level was 89 in the early stage. Conclusion: The chest CT has about 24 higher diagnostic sensitivity than the PCR test, in the early stage. GGO revealed a declining process and also indicates that GGO is an early symptom of the disease in CT scan. Linear opacity is the reason behind the initial dyspnea in coronavirus suffering patients referring to the medical centers. The extra-pulmonary lesions increase in the last stage of the disease that makes the patient�s worse. © 2021, The Author(s)

Involvement of PPAR-γ and p53 in DHA-induced apoptosis in Reh cells

Docosahexaenoeic acid (DHA, 22:6 n-3) is an omega-3 polyunsaturated fatty acid that is found in fish oil and exerts cytotoxic effect on a variety of cell lines. The molecular target, responsible for mediating this effect of DHA, still remains unknown. In this report, we presented experimental evidences for the role of PPAR-γ in conveying the cytotoxic effect of DHA. We showed that DHA induces apoptosis in Reh and Ramos cells and apoptotic effect of DHA is inhibited by the PPAR-γ antagonist GW9662, indicating that PPAR-γ functions as the mediator of the apoptotic effect of DHA. Furthermore, our result showed that DHA induces the PPAR-γ protein levels in both Reh and Ramos cells. Interestingly, DHA was found to induce the expression of p53 protein in Reh cells in a PPAR-γ-dependent manner. The up-regulation of p53 protein by DHA kinetically correlated with the activation of caspase 9, caspase 3, and induction of apoptosis, suggesting a role for p53 in DHA-mediated apoptosis in Reh cells. Taken together, these findings suggest a new signaling pathway, DHA-PPAR-γ-p53, in mediating the apoptotic effect of DHA in Reh cells. © Springer Science+Business Media, LLC 2007

Portable Microfluidic Integrated Plasmonic Platform for Pathogen Detection

Timely detection of infectious agents is critical in early diagnosis and treatment of infectious diseases. Conventional pathogen detection methods, such as enzyme linked immunosorbent assay (ELISA), culturing or polymerase chain reaction (PCR) require long assay times, and complex and expensive instruments, which are not adaptable to point-of-care (POC) needs at resource-constrained as well as primary care settings. Therefore, there is an unmet need to develop simple, rapid, and accurate methods for detection of pathogens at the POC. Here, we present a portable, multiplex, inexpensive microfluidic-integrated surface plasmon resonance (SPR) platform that detects and quantifies bacteria, i.e., Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) rapidly. The platform presented reliable capture and detection of E. coli at concentrations ranging from ∼105 to 3.2 × 107 CFUs/mL in phosphate buffered saline (PBS) and peritoneal dialysis (PD) fluid. The multiplexing and specificity capability of the platform was also tested with S. aureus samples. The presented platform technology could potentially be applicable to capture and detect other pathogens at the POC and primary care settings. © 2015, Nature Publishing Group. All rights reserved

Invariant Forms and Automorphisms of Locally Homogeneous Multisymplectic Manifolds

It is shown that the geometry of locally homogeneous multisymplectic manifolds (that is, smooth manifolds equipped with a closed nondegenerate form of degree > 1, which is locally homogeneous of degree k with respect to a local Euler field) is characterized by their automorphisms. Thus, locally homogeneous multisymplectic manifolds extend the family of classical geometries possessing a similar property: symplectic, volume and contact. The proof of the first result relies on the characterization of invariant differential forms with respect to the graded Lie algebra of infinitesimal automorphisms, and on the study of the local properties of Hamiltonian vector fields on locally multisymplectic manifolds. In particular it is proved that the group of multisymplectic diffeomorphisms acts (strongly locally) transitively on the manifold. It is also shown that the graded Lie algebra of infinitesimal automorphisms of a locally homogeneous multisymplectic manifold characterizes their multisymplectic diffeomorphisms.Comment: 25 p.; LaTeX file. The paper has been partially rewritten. Some terminology has been changed. The proof of some theorems and lemmas have been revised. The title and the abstract are slightly modified. An appendix is added. The bibliography is update

Development of Indirect Immunofluorescence Technique for the Identification of MRC5 Working Seed Cell

Diploid and continuous cell lines are used to propagate viral vaccines. At Human Viral Vaccine Department of Razi Vaccine and Serum Research Institute, MRC5 diploid cell is used for the development of live attenuated measles, mumps, rubella, and three types of poliovirus vaccines.  Additionally, three continuous cell lines (i.e., RK13, HeLa, and Vero) are applied in quality control tests. Accordingly, cell cross-contamination can occur at cell culture labs, hence controlling the identity and specificity of cells is essential. Indirect immunofluorescence is a sensitive, specific, and simple test for cell identification. The present study was designed to develop the in-house indirect immunofluorescence test (IIF) as follows: homemade polyclonal anti-MRC5 serum was prepared in rabbits, and cross-reactive antibodies to RK13, HeLa, and Vero cells were eliminated. The diploid and continuous cell lines were fixed on Teflon slide using cold methanol and acetone. The reproducibility of the in-house IIF test was evaluated using the agreement Kappa test.  The purity of the three batches of MRC5 working seed cell at Human Viral Vaccine Department of Razi institute was verified using IIF and no contamination with continuous cell lines was detected