Regulation of DNA synthesis and the cell cycle in human prostate cancer cells and lymphocytes by ovine uterine serpin

<p>Abstract</p> <p>Background</p> <p>Uterine serpins are members of the serine proteinase inhibitor superfamily. Like some other serpins, these proteins do not appear to be functional proteinase inhibitors. The most studied member of the group, ovine uterine serpin (OvUS), inhibits proliferation of several cell types including activated lymphocytes, bovine preimplantation embryos, and cell lines for lymphoma, canine primary osteosarcoma and human prostate cancer (PC-3) cells. The goal for the present study was to evaluate the mechanism by which OvUS inhibits cell proliferation. In particular, it was tested whether inhibition of DNA synthesis in PC-3 cells involves cytotoxic actions of OvUS or the induction of apoptosis. The effect of OvUS in the production of the autocrine and angiogenic cytokine interleukin (IL)-8 by PC-3 cells was also determined. Finally, it was tested whether OvUS blocks specific steps in the cell cycle using both PC-3 cells and lymphocytes.</p> <p>Results</p> <p>Recombinant OvUS blocked proliferation of PC-3 cells at concentrations as low as 8 μg/ml as determined by measurements of [³H]thymidine incorporation or ATP content per well. Treatment of PC-3 cells with OvUS did not cause cytotoxicity or apoptosis or alter interleukin-8 secretion into medium. Results from flow cytometry experiments showed that OvUS blocked the entry of PC-3 cells into S phase and the exit from G₂/M phase. In addition, OvUS blocked entry of lymphocytes into S phase following activation of proliferation with phytohemagglutinin.</p> <p>Conclusion</p> <p>Results indicate that OvUS acts to block cell proliferation through disruption of the cell cycle dynamics rather than induction of cytotoxicity or apoptosis. The finding that OvUS can regulate cell proliferation makes this one of only a few serpins that function to inhibit cell growth.</p

Disease Monitoring Parameters for Autoimmune Diseases

Autoimmune diseases are complex chronic multisystem disorders that are potentially life threatening. The etiology of autoimmune diseases is not known but genetic, hormonal, and environmental factors are found to be involved in their pathogenesis. The clinical course is usually very long and patients have circulating autoantibodies in their serum before the appearance of clinical signs and symptoms. Seventy-five percent of the autoimmune diseases occur in women and it is one of the top ten causes of death in women below the age of 65 years. Many women may possess irregular non-specific symptoms such fatigue, muscle pain, and joint pain because of the genes and may or may not progress to one or the other symptomatic autoimmune diseases leading to severe complications including organ failure and death. Increased death rates in women because of autoimmune diseases have been recently reported in the US and UK. Researchers have also reported a steep rise in economic burden due to autoimmune diseases. Early diagnosis of the autoimmune diseases may play an important role in modifying the course of disease progression. Following up of patients with autoimmune diseases on a regular basis with available prognostic tests will greatly reduce morbidity and possibly mortality in these patients. In this comprehensive review article, we have summarized available prognostic strategies and recommendations for common autoimmune disorders

Prognostic Biomarkers in Cardiovascular Diseases

The use of biomarkers as a reliable and reproducible indicative of the risk, severity, and progression of cardiovascular diseases (CVDs) may greatly enhance the prognostic capability of primary healthcare clinicians. In primary healthcare, the realistic and wise use of reliable biomarkers could minimize the time and costs for effective diagnosis and suitable personalized therapy for CVD patients. Therefore, the aim of the present scoping review is to evaluate the prognostic significance of biomarkers in the progression and monitoring of CVDs. The review was conducted according to the PRISMA-ScR guidelines. Eight databases were searched for articles published as of June 2021 using search terms: cardiovascular diseases AND biomarkers AND prognosis. A total of 21 studies were included in this scoping review. This review identified biomarkers BNP, cTnT yielded better accuracy of disease progression prediction in ACS and HF respectively. The availability of CVDs prognostic biomarkers in primary healthcare clinics could promote improved clinical outcomes of patients

Metal–Metal Bonding in Low-Coordinate Dicobalt Complexes Supported by Phosphinoamide Ligands

Homobimetallic dicobalt complexes featuring metal centers in different coordination environments have been synthesized, and their multielectron redox chemistry has been investigated. Treatment of CoX₂ with MesNKP^<i>i</i>Pr₂ leads to self-assembly of [(THF)­Co­(MesNP^<i>i</i>Pr₂)₂­(μ-X)­CoX] [X = Cl (<b>1</b>), I (<b>2</b>)], with one Co center bound to two amide donors and the other bound to two phosphine donors. Upon two-electron reduction, a ligand rearrangement occurs to generate the symmetric species (PMe₃)­Co­(MesNP^<i>i</i>Pr₂)₂­Co­(PMe₃) (<b>3</b>), where each Co has an identical mixed P/N donor set. One-electron oxidation of <b>3</b> to generate a mixed valence species promotes a ligand reararrangement back to an asymmetric configuration in [(THF)­Co­(MesNP^<i>i</i>Pr₂)₂­Co­(PMe₃)]­[PF₆] (<b>4</b>). Complexes <b>1</b>–<b>4</b> have been structurally characterized, and their metal–metal interactions are discussed in the context of computational results

ADMET informatics of Tetradecanoic acid (Myristic Acid) from ethyl acetate fraction of Moringa oleifera leaves

In-silico Computer-Aided Drug Design (CADD) often comprehends virtual screening (VS) of datasets of natural pharmaco-active compounds for drug discovery protocols. Plant Based Natural Products (PBNPs) still, remains to be a prime source of pharmaco-active compounds due to their unique chemical structural scaffolds and functionalities with distinct chemical characteristic feature from natural source that are much acquiescent to drug metabolism and kinetics. In the Post-COVID-Era number of publications pertaining to PBNPs and publicly accessible plant based natural product databases (PBNPDBs) has significantly increased. Moreover, PBNPs are important sources of inspiration or starting points to develop novel therapeutic agents. However, a well-structured, in-depth ADME/Tox profile of PBNPs has been limited or lacking for many of such compounds, this hampers the successful exploitation of PBNPs by pharma industries. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties play key roles in the discovery/ development of drugs, pesticides, food additives, consumer products, and industrial chemicals. In the present study, ADMET-informatics of Tetradecanoic Acid (Myristic Acid) from ethyl acetate fraction of Moringa oleifera leaves to predict drug metabolism and pharmacokinetics (DMPK) outcomes has been taken up. This work contributes to the deeper understanding of Myristic acid as major source of drug from commonly available medicinal plant - Moringa oleifera with immense therapeutic potential. The data generated herein could be useful for NP based lead generation programs. Keywords: Moringa oleifera; Secondary Metabolites; Bioactive Substances; Myristic acid (MA); DMPK; ADME/Tox; Natural Products (NPs); PBNPs; PBNPDB

ADMET informatics of Plant Derived n-Hexadecanoic Acid (Palmitic Acid) from ethyl acetate fraction of Moringa oleifera leaf extract

Palmitic Acid (PA) is known to exert multiple fundamental biological functions at cellular and tissue levels and its steady concentration is guaranteed by its endogenous synthesis by DNL. PA has been for a long time negatively represented for its detrimental health effects tailing its essential physiological attributes. PA has been portrayed to serve as a signalling molecule regulating the progression and development of many diseases at molecular level. Controversial data on the association of dietary PA with detrimental health effects has been related to several parameters such as fatty acid/ macronutrient imbalance by altered lipid metabolism, positive energy balance, excessive intake of carbohydrates, imbalance of dietary PA/PUFA, physiopathological conditions, presence of enhanced DNL and sedentary lifestyle. This may result in dyslipidemia, hyperglycemia, increased ectopic fat accumulation and increased inflammatory tone indicating that clear understanding of system based PA metabolism is still lacking. In the present study an attempt has been made to bring out the absorption, distribution, metabolism, elimination and toxicity profile of PA. Results are expected to have some implications in elucidating the molecular mechanisms that regulates pathophysiological events involved in hyperglycemia/ hyperlipidemia-induced complications associated with diabesity and CVD. Besides it may provide a better understanding to identify key molecular targets for therapeutic management of PA induced metabolic disorders. Keywords: Moringa oleifera; MOLE; Bioactive Secondary Metabolites; ADME/Tox; Natural Products (NPs); PBNPs; PDHA; n-Hexadecanoic Acid (nHDA); Palmitic Acid (PA

Geotechnical investigation on compacted clay liner blended with reactive material

Clays are used for the construction of waste containment barriers, mainly because of its low hydraulic conductivity. In general, at several places, it may not be possible to obtain the clay satisfying the essential requirements as a liner material. Hence at many places commercially available bentonites is often used for the construction of clay liners. Bentonite undergoes significant changes in volume upon saturation. Several physical and chemical stabilization methods are in practice to stabilize the bentonite. Previous studies report that contaminants with high concentrations attack the clay minerals leading to an increase in their permeability. Exfoliated vermiculite, finds several applications in construction industry, and it is also found to be good absorbent material. Hence this study has been carried out to find the optimal percentage of vermiculite that can be added to the bentonite so that it satisfies the essential requirements of clay liners and it can also absorb the heavy metals from the contaminants. The tests for index properties and engineering properties of bentonite-vermiculite mixtures were performed. The test results show that 30% of vermiculite can be added to bentonite, so that the essential requirements of the liner can be maintained