Therapeutic Potential of Mesenchymal Stem Cells and Their Secretome in the Treatment of SARS-CoV-2-Induced Acute Respiratory Distress Syndrome.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent responsible for the development of a new coronavirus disease (COVID-19), is a highly transmittable virus which, in just ten months, infected more than 40 million people in 214 countries worldwide. After inhalation, aerosols containing SARS-CoV-2 penetrate to the depths of the lungs and cause severe pneumonia, alveolar injury, and life-threatening acute respiratory distress syndrome (ARDS). Since there are no specific drugs or vaccines available to cure or prevent COVID-19 infection and COVID-19-related ARDS, a new therapeutic agent which will support oxygen supply and, at the same time, efficiently alleviate SARS-CoV-2-induced lung inflammation is urgently needed. Due to their potent immuno- and angiomodulatory characteristics, mesenchymal stem cells (MSCs) may increase oxygen supply in the lungs and may efficiently alleviate ongoing lung inflammation, including SARS-CoV-2-induced ARDS. In this review article, we described molecular mechanisms that are responsible for MSC-based modulation of immune cells which play a pathogenic role in the development of SARS-CoV-2-induced ARDS and we provided a brief outline of already conducted and ongoing clinical studies that increase our understanding about the therapeutic potential of MSCs and their secretome in the therapy of COVID-19-related ARDS

Tumor necrosis factor-alpha as differential diagnostic marker for patients with fever of unknown origin

© 2019, University of Kragujevac, Faculty of Science. All rights reserved. Febrile conditions of unidentified origin are still unknown in modern medicine despite the development of diagnostic procedures. There are various agents of long-term temperature encompassing numerous infectious or non-infectious diseases. The aim of this study was to determine if there was a statistically significant difference in the values of proinfl ammatory cytokines (IL-1, TNFa, IL-6) in patients who meet the criteria for febrile conditions of unidentified origin, between the group of infectious, malignant, rheumatic, “other” diseases and undiagnosed patients. The study was conducted in the Immunology laboratory of the Center for Molecular Medicine and Stem Cells Research of the Faculty of Medical Sciences in Kragujevac. Blood samples were taken from patients tested at the Clinic for Infectious Diseases, of the Clinical Center of Kragujevac, in the period from 2014 to 2016. The study included 70 patients. The measured values of the level of TNFa showed significantly higher values in a group of malignant diseases than in the group of infectious diseases, while the values of IL-1 and IL-6 did not show statistical significance. TNFa can improve diagnosing in case of patients with an unknown febrile condition, which can shorten the length of the hospital stay and reduce the volume of performance of diagnostic procedures

Synthesis, Characterization and Biological Studies of Organoselenium trans-Palladium(II) Complexes

Background: Over the years, transition metal complexes have exhibited significant antimicrobial and antitumor activity. It all started with cisplatin discovery, but due to the large number of side effects it shows, there is a growing need to find a new metal-based compound with higher selectivity and activity on more tumors. Objectives: Two novel trans-palladium(II) complexes with organoselenium compounds as ligands, [Pd(L1)2Cl2] (L1 = 5-(phenylselanylmethyl)-dihydrofuran-2(3H)-one) and [Pd(L2)2Cl2] (L2 = 2- methyl-5-(phenylselanylmethyl)- tetrahydrofuran) were synthesized, in the text referred to as Pd-Se1 and Pd-Se2. Also, a structurally similar trans-palladium(II) complex, [Pd(L3)2Cl2] (L3= 2,2- dimethyl-3-(phenylselanylmethyl)-tetrahydro-2H-pyran ) was synthesized according to an already published work and is referred to as Pd-Se3. The interaction of synthesized complexes with DNA and bovine serum albumin was observed. Also, antimicrobial activity and in vitro testing, cell viability, and cytotoxic effects of synthesized ligands and complexes on human epithelial colorectal cancer cell line HCT-116 were studied. Molecular docking simulations were performed to understand better the binding modes of the complexes reported in this paper with DNA and BSA, as well as to comprehend their antimicrobial activity. Methods: The interactions of the synthesized complexes with DNA and bovine serum albumin were done using UV-Vis and emission spectral studies as well as docking studies. Antimicrobial activity was tested by determining the minimum inhibitory concentrations (MIC) and minimum microbicidal concentration (MMC) using the resazurin microdilution plate method. Cytotoxic activity on cancer cells was studied by MTT test. Results: The Pd(II) complexes showed a significant binding affinity for calf thymus DNA and bovine serum albumin by UV-Vis and emission spectral studies. The intensity of antimicrobial activity varied with the complexes Pd-Se1 and Pd-Se3, showing significantly higher activity than the corresponding ligand. The most significant activity was shown on Pseudomonas aeruginosa. Under standardized laboratory conditions for in vitro testing, cell viability and cytotoxic effects of synthesized ligands and complexes were studied on human epithelial colorectal cancer cell line HCT-116, where Pd-Se2 showed some significant cytotoxic effects. Conclusion: The newly synthesized complexes have the potential to be further investigated as metallodrugs.Publishe

Molecular Mechanisms Responsible for Mesenchymal Stem Cell-Based Treatment of Viral Diseases

Mesenchymal stem cells (MSCs) are adult, immunomodulatory stem cells which reside in almost all postnatal tissues. Viral antigens and damage-associated molecular patterns released from injured and infected cells activate MSCs, which elicit strong antiviral immune response. MSC-sourced interferons and inflammatory cytokines modulate the cytotoxicity of NK cells and CTLs, enhance the antigen-presentation properties of DCs and macrophages, regulate cytokine synthesis in CD4+ T helper cells and promote antibody production in B cells. After the elimination of viral pathogens, MSCs produce immunoregulatory cytokines and trophic factors, prevent the over-activation of immune cells and promote tissue repair and regeneration. In this review article, we summarize the current knowledge on the molecular mechanisms that are responsible for the MSC-dependent elimination of virus-infected cells, and we emphasize the therapeutic potential of MSCs and their secretomes in the treatment of viral diseases

Malaria in the 21st century - Still a threatening problem

© 2019, Serbia Medical Society. All rights reserved. There are six parasite species (P. falciparum, P. vivax, P. ovale curtisi, P. ovale wallikeri, P. malariae, and P. knowlesi) that cause malaria in humans. P. falciparum is responsible for most malaria-related deaths globally. P. vivax is the dominant malaria parasite in most countries outside of the Sub-Saharan Africa. In 2016, 91 countries reported a total of 216 million cases of malaria. The global tally of malaria deaths reached 445,000. In 2016, 24 cases of imported malaria were registered in the Republic of Serbia, with an incidence of 0.33/100,000. According to the World Health Organization recommendations, every suspected malaria case should be confirmed by microscopy or a rapid diagnostic test before treatment. The main stone of antimalarial therapy should be artemisinin-based combinations. Since malaria occurs in Europe as an imported (though rarely also autochthonous and a hospital-borne infection), the objective of this paper is to point out current problems and attitudes in the diagnosis and treatment of malaria, without entering the data field significant for professionals (infectologists, epidemiologists, intensivists)

Interplay Between the Immunohistochemical Expression of P53 and the Proliferation Index in the Keratinocyte Tumors of the Skin

P53 is important for cell cycle regulation, and its overexpression is seen in malignant tumors. We examined correlation between p53 expression and cell proliferation, and its role in the pathogenesis of keratinocyte skin tumors. We used biopsies from patients with squamous cell carcinoma, actinic keratosis and keratoacanthoma. We examined crosssections stained with HE and using anti-cytokeratin, antip53 and anti-Ki67 antibodies

Sudden death syndrome caused by cardiac tumor

© 2020, Serbian Medical Society. All rights reserved. Cardiac tumors are not a common pathology. However, due to their occurrence in the vital organ, they bare an extremely important clinical significance. According to biological behavior, they are divided into 2 groups, primary (benign and malignant), which are less frequent and secondary (metastatic), which are more common. Among all primary benign cardiac tumors, myxoma is the one that occurs most often. A great number of studies indicate that it originates from multipotent mesenchymal cells of the septum of the left atrium. It is due to its localization that some authors consider it potentially malignant. This paper presents a case of cardiac myxoma which is echocardiographically diagnosed in a 34-year-old woman who died suddenly, several days before the scheduled surgery. The diagnosis of the disease was confirmed after the autopsy, by a routine haematoxylin-eosin (H&E) staining method and an additional immunohistochemistry method (IHC). By presenting a rare clinical case, we emphasize the fact that every diagnosed cardiac tumor requires immediate cardiac surgery without delay

Encephalopathy during H1N1 influenza a virus infection

© 2016, University of Kragujevac, Faculty of Science. All Rights Reserved. Influenza virus type A is known for its capacity to transform its antigenic structure and create new viral subtypes. The clinical picture varies from non-febrile, mild upper respiratory tract infection to severe or fatal pneumonia. Neurological complications include encephalitis, encephalopathy, Reye’s syndrome and other neurological diseases. Patients with encephalopathy exhibit a disturbed state of consciousness lasting more than 24 hours, and patients with encephalitis exhibit high temperature, focal neurological signs and pathological CSF results in addition to disturbed state of consciousness. A 54-year old, previously healthy male farmer was hospitalized at the Clinic for Infectious Diseases of the Clinical Centre Kragujevac on the fifth day of disease. In addition to general symptoms of the disease, the clinical picture was dominated by a disturbed state of consciousness (Glasgow Coma Scale score <8). The aetiological agent was an H1N1 influenza A virus, which was isolated from nasopharyngeal secretions. No other causes of infection were demonstrated from both serum and cerebrospinal fluid specimens. Interstitial pneumonia was detected by radiographic examination of the chest. There were also some changes present in the EEG. The patient was cured without consequences. Because our country is in a whirlwind of pandemic H1N1 virus activity, we should think of all the possible complications that this virus can produce regardless of the epidemiological data and the clinical picture

Analysis Of Clinical, Haematological And Biochemical Parameters In Patients With Infectious Mononucleosis

Primary infection with Epstein-Barr virus (EBV) usually occurs in early childhood and often does not present clinical symptoms. More than 90% of adults are infected with this virus. A primary infection that occurs in adolescence or adulthood is usually clinically presented as infectious mononucleosis with a triad of symptoms: fever, lymphadenopathy and pharyngitis. Our retrospective study included 51 patients with a median age of 17 (9-23) years and serologically confirmed infectious mononucleosis. All patients with infectious mononucleosis were treated at the Clinic for Infectious Diseases at the Clinical Center in Kragujevac during 2013. We analysed the clinical, haematological and laboratory parameters of patients. The aspartate-aminotransferase levels were increased in 40 patients, with a mean value of 116.24 (±93.22); the alanine-aminotransferase levels were increased in 44 patients, with a mean value of 189.24 (±196.69). Lymphadenopathy was the most common clinical feature upon admission in 49 patients (96%); 38 patients (74.5%) had splenomegaly, and 20 (39%) had hepatomegaly. Twenty-six patients (51%) had leukocytosis with lymphocytosis, while 15 (75%) of the 20 who had a normal leukocyte count also had lymphocytosis. In the present study, we updated the clinical, haematological and laboratory parameters, which may lead to the establishment of an accurate diagnosis and promote further treatment of the patients

The Analysis of Risk Factors and Clinical-Demographic Characteristics of Patients with Clostridium Dificille Infection as Well as The Outcome of Their Treatment

Pseudomembranous colitis is a frequent nosocomial infection associated with significant morbidity and mortality. Clostridium difficile infection incidence most frequently increases due to unreasonable antibiotic use and the appearance of new hypervirulent bacterial strains, which leads to prolonged hospitalization and an increase in the total cost of hospital treatment