Publications by authors named "Miriana Stan"

8 Publications

  • Page 1 of 1

Obesity ‑ a risk factor for increased COVID‑19 prevalence, severity and lethality (Review).

Mol Med Rep 2020 Jul 5;22(1):9-19. Epub 2020 May 5.

Laboratory of Toxicology, Medical School, University of Crete, 71409 Heraklion, Greece.

Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are a group of viruses that cause infections in the human respiratory tract, which can be characterized clinically from mild to fatal. The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is the virus responsible. The global spread of COVID‑19 can be described as the worst pandemic in humanity in the last century. To date, COVID‑19 has infected more than 3,000,000 people worldwide and killed more than 200,000 people. All age groups can be infected from the virus, but more serious symptoms that can possibly result in death are observed in older people and those with underlying medical conditions such as cardiovascular and pulmonary disease. Novel data report more severe symptoms and even a negative prognosis for the obese patients. A growing body of evidence connects obesity with COVID‑19 and a number of mechanisms from immune system activity attenuation to chronic inflammation are implicated. Lipid peroxidation creates reactive lipid aldehydes which in a patient with metabolic disorder and COVID‑19 will affect its prognosis. Finally, pregnancy‑associated obesity needs to be studied further in connection to COVID‑19 as this infection could pose high risk both to pregnant women and the fetus.
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http://dx.doi.org/10.3892/mmr.2020.11127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248467PMC
July 2020

Effects of Cetylated Fatty Acids Mixture from Celadrin on Chondrogenesis and Inflammation with Impact on Osteoarthritis.

Cartilage 2020 01 29;11(1):88-97. Epub 2018 May 29.

"Sfanta Maria" Clinical Hospital, "Carol Davila" University, Medicine and Pharmacy Faculty, Internal and Rheumatology Department, Bucharest, Romania.

Objective: Cetylated fatty acids are a group of naturally occurring fats of plant and/or animal origin. Cetyl myristoleate, in particular, was initially involved in osteoarthritis related research as its therapeutic administration prevented experimentally induced arthritis in Swiss Albino mice. In this context, the aim of our study was to investigate the possible mechanisms of Celadrin cetylated fatty acids action at the cellular level inflammation related pain relief and chondrogenesis.

Design: For this, we tested the effects of the cetylated fatty acids mixture from Celadrin on an scaffold-free 3-dimensional mesenchymal stem cells culture model of chondrogenesis. Furthermore, we treated stimulated mouse macrophage cells with the cetylated fatty acids mixture to investigate the expression profile of secreted inflammatory cytokines.

Results: The cetylated fatty acids mixture from Celadrin significantly decreased the production of IL-6, MCP-1, and TNF, key regulators of the inflammatory process, in stimulated RAW264.7 mouse macrophage cells. The treatment with cetylated fatty acids mixture initiated and propagated the process of chondrogenesis as demonstrated by the increased expression and deposition of chondrogenic markers by the differentiating mesenchymal cells.

Conclusion: The cetylated fatty acids mixture from Celadrin reduces inflammation by significantly decreasing the expression of IL-6, MCP-1, and TNF in stimulated RAW264.7 mouse macrophage cells. These compounds facilitate the chondrogenic differentiation process of human adipose-derived stem cells by stimulating the expression of chondrogenic markers under chondrogenic induction conditions.
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http://dx.doi.org/10.1177/1947603518775798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921950PMC
January 2020

Poly(HydroxyButyrate-co-HydroxyValerate) (PHBHV) Nanocarriers for Silymarin Release as Adjuvant Therapy in Colo-rectal Cancer.

Front Pharmacol 2017 2;8:508. Epub 2017 Aug 2.

Department of Toxicology, Faculty of Pharmacy, Carol Davila University of Medicine and PharmacyBucharest, Romania.

The aim of this study was to address one of the major challenges of the actual era of nanomedicine namely, the bioavailability of poorly water soluble drugs such as Silymarin. We developed new, biodegradable, and biocompatible nanosized shuttles for Silymarin targeted delivery in colon-cancer cells. The design of these 100 nm sized carrier nanoparticles was based on natural polymers and their biological properties such as cellular uptake potential, cytotoxicity and 3D penetrability were tested using a colon cancer cell line (HT-29) as the culture model. Comparative scanning electron microscopy (SEM) and atomic force microscopy (AFM) measurements demonstrated that the Silymarin loaded Poly(3-HydroxyButyrate-co-3-HydroxyValerate) (PHBHV) nanocarriers significantly decreased HT-29 cells viability after 6 and 24 h of treatment. Moreover, like toxicity studies on multicellular tumor spheroids showed that the Silymarin loaded PHBHV nanocarriers are able to penetrate 3D micro tumors and significantly reduce their size.
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http://dx.doi.org/10.3389/fphar.2017.00508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5539237PMC
August 2017

Worldwide legislative challenges related to psychoactive drugs.

Daru 2017 Jun 2;25(1):14. Epub 2017 Jun 2.

University of Crete, Medical School, Department of Toxicology and Forensic Sciences, Heraklion, Greece.

The discovery of a "new" psychoactive substance is a relatively exceptional event, while the regulatory response usually involved the assessment of risks to public health and inclusion of the novel substance in the national list of controlled substances. However, in recent years we have witnessed the rapid emergence of new chemical substances, which elude international control and pose a challenge to existing processes and a threat to the credibility of control systems. We currently review and present characteristics of these legal and illegal new substances and issues regarding their global monitoring and regulatory measures already taken, or in the process of being taken, for their control. The concept of prohibition applied in active substance-related legislation is rather hazard ridden as balance is required between the ban on substances of potential therapeutic use and the access on the market of high-risk substances. Current and future laws regarding psychoactive compounds.
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http://dx.doi.org/10.1186/s40199-017-0180-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455135PMC
June 2017

Environmental metal contamination and health impact assessment in two industrial regions of Romania.

Sci Total Environ 2017 Feb 16;580:984-995. Epub 2016 Dec 16.

Department of Forensic Sciences and Toxicology, University of Crete, Heraklion, Greece.

We investigated two Romanian industrial regions- Copşa Mică and Zlatna, to assess the current situation of soil pollution and bioaccumulation of Pb, Cd, Cu and Zn in different vegetable species and possible risks to consumers. Both total and mobile forms of the metals were determined in soil samples, and metal content in the edible parts of root vegetable samples was also assessed. The concentrations of Pb and Zn in soil were higher in Copşa Mică than in Zlatna (566mg/kg vs 271mg/kg for Pb and 1143mg/kg vs 368mg/kg for Zn)·The metal mobility in soil from Copsa Mica decreases in the order Zn>Cu>Cd>Pb (1.88mg/kg, 0.40mg/kg, 0.22mg/kg, 0.16mg/kg, respectively), while in Zlatna, the order was Cu>Zn>Pb>Cd (0.88mg/kg, 0.29mg/kg, 0.04mg/kg, 0.01mg/kg, respectively), apparently depending on metal and soil conditions. In Copsa Mica, the amount of Pb and Cd in vegetable samples exceeded the maximum permissible limits in carrots (median concentration 0.32mg/kg for Pb and Cd) and in yellow onions (median concentration 0.24mg/kg for Cd). In Zlatna region, the content of Cd exceeded the maximum limits in yellow onions (median concentration 0.11mg/kg). The amount of Pb was higher than the maximum acceptable level in carrots from the Zlatna region (median concentration 0.12mg/kg). Cu and Zn levels were within the normal range in all vegetable samples. In the Zlatna region, the transfer factors for Pb and Cd were higher in carrots (median values of 9.9 for Pb and 21.0 for Cd) compared to carrots harvested in Copsa Mica (median values of 4.0 for Pb and 2.0 for Cd). Daily intake rates of metals through local vegetable consumption exceeded the limit values established by the European Food Safety Authority for Pb (1.2 to 2.4 times) and Cd (5.5 to 9.1 times) in both regions, with potential adverse health effects for the local population. The results highlight the need for total soil remediation action before fruit and vegetables produced in these polluted areas can be safely consumed.
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http://dx.doi.org/10.1016/j.scitotenv.2016.12.053DOI Listing
February 2017

Colon Cancer Cells Gene Expression Signature As Response to 5- Fluorouracil, Oxaliplatin, and Folinic Acid Treatment.

Front Pharmacol 2016 23;7:172. Epub 2016 Jun 23.

Department of Toxicology and Forensic Sciences, Medical School, University of Crete Heraklion, Greece.

5-FU cytotoxicity mechanism has been assigned both to the miss-incorporation of fluoronucleotides into RNA and DNA and to the inhibition of thymidylate synthase. 5-FU is one of the most widely used chemotherapeutic drugs, although it has severe side effects that may vary between patients. Pharmacogenetic studies related to 5-FU have been traditionally focused on the rate-limiting catabolic enzyme, dihydropyrimidine dehydrogenase that breaks 80-85% of 5-FU into its inactive metabolite. Choosing the right dosing scheme and chemotherapy strategy for each individual patient remains challenging for personalized chemotherapy management. In the general effort toward reduction of colorectal cancer mortality, in vitro screening studies play a very important role. To accelerate translation research, increasing interest has been focused on using in vivo-like models such as three-dimensional spheroids. The development of higher throughput assays to quantify phenotypic changes in spheroids is an active research area. Consequently, in this study we used the microarray technology to reveal the HT-29 colorectal adenocarcinoma cells gene expression signature as response to 5-FU/OXP/FA treatment in a state of the art 3D culture system. We report here an increased reactive oxygen species production under treatment, correlated with a decrease in cell viability and proliferation potential. With respect to the HT-29 cells gene expression under the treatment with 5-FU/OXP/FA, we found 15.247 genes that were significantly differentially expressed (p < 0.05) with a fold change higher that two-fold. Among these, 7136 genes were upregulated and 8111 genes were downregulated under experimental conditions as compared to untreated cells. The most relevant and statistic significant (p < 0.01) pathways in the experiment are associated with the genes that displayed significant differential expression and are related to intracellular signaling, oxidative stress, apoptosis, and cancer.
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http://dx.doi.org/10.3389/fphar.2016.00172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917556PMC
July 2016

Management of rheumatoid arthritis: Impact and risks of various therapeutic approaches.

Exp Ther Med 2016 Apr 2;11(4):1177-1183. Epub 2016 Feb 2.

Department of Toxicology, Faculty of Pharmacy, 'Carol Davila' University of Medicine and Pharmacy, Bucharest 020956, Romania.

Rheumatic diseases are highly prevalent chronic disorders and the leading cause of physical disability worldwide, with a marked socio-economic impact. Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of unknown etiology with an autoimmune pathogenesis, characterised by arthropathy with chronic, deforming, destructive evolution and multiple systemic manifestations. The management of RA has undergone significant changes as far as objectives and approaches are concerned, ending in the current strategy known as 'treat to target'. The therapeutic array of RA includes several categories of medicinal products, of varying potential. There are several criteria for the classification of medicinal products used against this disease, one of the most important and modern of which divides such substances according to their effects on the progress of the disease: symptom-modifying antirheumatic drugs (including non-steroidal anti-inflammatory drugs and corticoids), disease-modifying antirheumatic drugs (including various substances, such as gold salts, antimalarials, sulfasalazine, D-penicillamine; non-specific immunosuppressive medication, such as methotrexate, cyclophosphamide, azathioprine and leflunomide) and biological therapy is a recent addition, providing new insight into the treatment of this disease. The selection of the optimal therapy for RA should be based on guidelines and recommendations, but also on clinical particular aspects and patient preferences.
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http://dx.doi.org/10.3892/etm.2016.3045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812232PMC
April 2016

Impact of multicellular tumor spheroids as an in vivo‑like tumor model on anticancer drug response.

Int J Oncol 2016 Jun 1;48(6):2295-302. Epub 2016 Apr 1.

Department of Surgery, 'Sf. Ioan' Emergency Clinical Hospital, 'Carol Davila' University of Medicine and Pharmacy, Bucharest 042122, Romania.

The incidence of colorectal cancer is higher in men than in women, amounting to 15% of cancer-related diseases as a whole. As such, undesirable effects, arising from the administration of current chemotherapeutic agents (the FOLFIRI/FOLFOX combinations), which are exerted on the remaining non-cancerous tissues and/or cells, have contributed to the occurrence of resistance to multiple drugs, thus markedly reducing their efficacy. However, the delivery of chemotherapeutic agents may be improved and their action may be more selectively targeted to diseased tissues/cells by means of developing biotechnologies and nano‑techniques. Thus, the current focus is on creating biological tissue and related tumor models, by means of three‑dimensional (3D) spheres, in an attempt to bridge the gap between results obtained in the pre‑clinical phase and promising outcomes obtained in clinical trials. For this purpose, the characterization and use of so‑called 'multicellular tumor spheroids', may prove to be invaluable. In this study, we focus on describing the efficacy of a model 3D system as compared to the traditional 2D tumor spheres in determining drug response, highlighting a potentially greater effect of the drugs following the encapsulation of respective liposomes. The results obtained demonstrate the successful preparation of a suspension of liposomes loaded with folinic acid, oxaliplatin and 5‑fluorouracil (5‑FU), and loaded with meso‑tetra (4‑sulfonatophenyl) porphyrin. Following its use on HT‑29 colorectal cancer cells, an important comparative reduction was noted in the viability of the HT‑29 cells, demonstrating the efficacy of multicellular tumor spheroids carrying liposomes loaded with therapeutic drugs. These findings indicate that the method of drug encapsulation in liposomes may improve the treatment efficacy of chemotherapeutic agents.
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http://dx.doi.org/10.3892/ijo.2016.3467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867843PMC
June 2016