forrás: https://medpublics.com/docs/gyulladas_es
2022-05-04 12:19:43
The connection between inflammation and tumorigenesis is well-established and in the last decade has received a great deal of supporting evidence from genetic, pharmacological, and epidemiological data. Inflammatory bowel disease is an important risk factor for the development of colon cancer. Inflammation is also likely to be involved with other forms of sporadic as well as heritable colon cancer. The molecular mechanisms by which inflammation promotes cancer development are still being uncovered and could differ between colitis-associated and other forms of colorectal cancer. Recent work has elucidated the role of distinct immune cells, cytokines, and other immune mediators in virtually all steps of colon tumorigenesis, including initiation, promotion, progression, and metastasis. These mechanisms, as well as new approaches to prevention and therapy, are discussed in this review.
forrás: http://medpublics.com/docs/OlimpiqSXC_Retinal.pdf
2021-06-23 10:37:34
Aim: To determine whether treatment with the stem cell stimulator Olimpiq® Stem×Cell prevents increase of retinal and renal vascular permeability in alloxan-induced diabetic rats. Materials and Methods: Two groups of Wistar rats were made diabetic by single intraperitoneal injection of Alloxan. The third, the control group, received vehicle alone. One diabetic group received Olimpiq® Stem×Cell treatment for 4 weeks. The permeability of the blood–retinal barrier (BRB) and renal vessels were measured by the extravasation of fluorescein–labeled bovine serum albumin. Results: Six weeks subsequently to Alloxan injection, significantly elevated the tissue fluorescence, the renal vascular leakage and BRB breakdown was demonstrated in the diabetic group, compared to the nondiabetic group. Olimpiq® Stem×Cell treatment significantly reduced the BRB breakdown, tissue fluorescence, and vascular leakage. Conclusion: Olimpiq® Stem×Cell would be a useful choice of treatment for complications associated with increased vascular permeability of diabetes, such as retinopathy or nephropathy.
forrás: https://pubmed.ncbi.nlm.nih.gov/21079686/
2021-01-22 12:16:26
Increasing the intracellular Zn(2+) concentration with zinc-ionophores like pyrithione (PT) can efficiently impair the replication of a variety of RNA viruses, including poliovirus and influenza virus. For some viruses this effect has been attributed to interference with viral polyprotein processing. In this study we demonstrate that the combination of Zn(2+) and PT at low concentrations (2 µM Zn(2+) and 2 µM PT) inhibits the replication of SARS-coronavirus (SARS-CoV) and equine arteritis virus (EAV) in cell culture. The RNA synthesis of these two distantly related nidoviruses is catalyzed by an RNA-dependent RNA polymerase (RdRp), which is the core enzyme of their multiprotein replication and transcription complex (RTC). Using an activity assay for RTCs isolated from cells infected with SARS-CoV or EAV--thus eliminating the need for PT to transport Zn(2+) across the plasma membrane--we show that Zn(2+) efficiently inhibits the RNA-synthesizing activity of the RTCs of both viruses. Enzymatic studies using recombinant RdRps (SARS-CoV nsp12 and EAV nsp9) purified from E. coli subsequently revealed that Zn(2+) directly inhibited the in vitro activity of both nidovirus polymerases. More specifically, Zn(2+) was found to block the initiation step of EAV RNA synthesis, whereas in the case of the SARS-CoV RdRp elongation was inhibited and template binding reduced. By chelating Zn(2+) with MgEDTA, the inhibitory effect of the divalent cation could be reversed, which provides a novel experimental tool for in vitro studies of the molecular details of nidovirus replication and transcription.
forrás: https://pubmed.ncbi.nlm.nih.gov/32125455/
2021-01-22 11:19:04
Josef Penninger is the founder and a shareholder of Apeiron, the company that makes rhACE2. Arthur Slutsky has been a paid consultant for Apeiron. No other conflicts of interested have been reported.
forrás: https://app.dimensions.ai/details/publication/pub.1125450507
2021-01-22 10:57:07
In the new millennium, the outbreak of new coronavirus has happened three times: SARS-CoV, MERS-CoV, and 2019-nCoV. Unfortunately, we still have no pharmaceutical weapons against the diseases caused by these viruses. The pandemic of 2019-nCoV reminds us of the urgency to search new drugs with totally different mechanism that may target the weaknesses specific to coronaviruses. Herein, we disclose a new targeted oxidation strategy (TOS II) leveraging non-covalent interactions potentially to oxidize and inhibit the activities of cytosolic thiol proteins via thiol/thiolate oxidation to disulfide (TOD). Quantum mechanical calculations show encouraging results supporting the feasibility to selectively oxidize thiol of targeted proteins via TOS II even in relatively reducing cytosolic microenvironments. Molecular docking against the two thiol proteases Mpro and PLpro of 2019-nCoV provide evidence to support a TOS II mechanism for two experimentally identified anti-2019-nCoV disulfide oxidants: disulfiram and PX-12. Remarkably, disulfiram is an anti-alcoholism drug approved by FDA 70 years ago, thus it can be immediately used in phase III clinical trial for anti-2019-nCoV treatment. Finally, a preliminary list of promising TOS II drug candidates targeting the two thiol proteases of 2019-nCoV are proposed upon virtual screening of 32143 disulfides
