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High-Risk Human Papillomavirus in Patients with Oral Carcinoma and Oral Potentially Malignant Disorders in Serbia—A Pilot Study
Get PDFBackground and Objectives: Oral squamous cell carcinoma (OSCC) accounts for about 95% of oral cancers. It represents a serious public health problem due to the high degree of morbidity and mortality, as well as multifactorial etiology. Human papillomavirus (HPV) infection is a well-documented risk factor for oropharyngeal carcinoma, but its role in oral carcinogenesis is still debatable. Our aim was to investigate the differences in the prevalence of high-risk HPV genotypes (HR-HPV) in patients with OSCC and oral potentially malignant disorders (OPMD) from that of healthy subjects. Materials and Methods: A total of 90 subjects were included in the cross-sectional study and divided into three groups of 30 patients each: (1) patients with OSCC, (2) patients with OPMD, and (3) healthy subjects. We examined the presence of 12 HR-HPV genotypes in the obtained biological material (oral swabs) using real-time PCR. Results: One or more of the 12 tested HR-HPV genotypes were detected in 5/30 patients with OSCC and 2/30 with OPMD, whereas no healthy subjects were positive for any of the tested genotypes. There was a statistically significant difference in nodal involvement between HPV-positive and HPV-negative patients with OSCC. Conclusions: Oral HR-HPV was detected in patients with oral premalignant and malignant lesions but not in healthy individuals, suggesting a possible role in oral carcinogenesis. Broad HR-HPV panel testing could increase the sensitivity of risk assessment and screening for OSCC
Uticaj Doksiciklina na regenerativni potencijal mezenhimskih matičnih ćelija periodoncijuma
Get PDFParodontopatija je hronično progresivno inflamatorno oboljenje tkiva parodoncijuma uzrokovano bakterijama zubnog plaka. Destrukcija parodoncijuma je posledica prekomerne aktivacije inflamatornog odgovora domaćina na bakterijsku infekciju i posledične produkcije citokina uključujući Interleukin-17 (IL-17). Lečenje parodontopatije podrazumeva i sistemsku primenu oralnih antibiotika poput doksociklina. Ovaj antibiotik iz klase tetraciklina ispoljava kako antibakterijska, tako i antiinflamatorna svojstva, a poznato je da utiče i na reparaciju tkiva i metabolizam alveolarnih kostiju.
Cilj ove studije je bio da utvrdimo da li doksociklin utiče na regenerativni potencijal mezenhimskih matičnih ćelija periodoncijuma (PDL-MMĆ) tretiranih sa IL-17. Naši rezultati su pokazali da doksociklin značajno smanjuje stimulativni efekat IL-17 na migraciju i ekspresiju matriksne metaloproteinaze 2 u PDL-MMĆ. Pored toga, doksociklin stimuliše osteogenu diferencijaciju PDL-MMĆ poništavajući inhibitorni efekat IL-17 na osteogenezu ovih ćelija. Analize ćelijske respiracije su otkrile da doksociklin smanjuje stopu potrošnje kiseonika i mitohondrijalnu biogenezu u IL-17-tretiranim PDL-MMĆ. Pokazana pro-regenerativna svojstva doksociklina u inflamatornom okruženju ukazuju na potencijal njegove primene u razvoju novih pristupa za terapiju parodontopatije
Nutritional and Anthropometric Status of Serbian Adults 10–74 Years Old: Results from European Food Safety Authority (EFSA) EU Menu Food Consumption Survey 2017–2021
Get PDFThe Serbian National Food Consumption Survey on adults from 10 to 74 years old, including pregnant women and vegetarians, was conducted in compliance with the EFSA EU Menu project support and guidance from 2017 to 2022. Valid data were collected from a total of 3018 participants with 856 adolescents aged 10 to 17 years, 1155 adults aged 18 to 64, 581 elderly subjects aged 65 to 74 years, 145 pregnant women, and 281 persons following a vegetarian diet. Data collection was conducted using a national Survey Pack designed for the project, including the following: a general questionnaire, an age-appropriate Food Propensity Questionnaire, an International Physical Activity Questionnaire, and 24 h dietary recall. The advanced nutritional platform Diet Assess and Plan (DAP) was applied for data storage, processing, and the creation of the final dataset for transfer to EFSA. The Serbian food composition database was used and updated during the project as a resource of food information for all foods and recipes that were consumed by the study cohort. Regardless of age and
gender category, the majority (56%) of adults had normal weight according to the Body Mass Index,while 21% were overweight, and 15.5% were underweight. The average daily energy intake was 2178.72 kcal, while overall contributions of carbohydrates, protein, and fat to the total energy intake were 43.37%, 15.47%, and 41.16%, respectively. The proportions of macronutrient intake deviated from the dietary reference values, particularly for fat, which was often too high, where sunflower oil was the major source of fat in diets. Out of the 3018 participants, 98% had breakfast, 99% had lunch,
and 95% had dinner, while approx. 80% had snacks between main meals. The highest energy intake was recorded during lunch, 706.5 kcal (32% TE). The survey results provide valuable insight into the nutritional status and dietary habits of adults from 10 to 74 years old living in Serbia. The Serbian food consumption database serves as an evidence platform for decision-making processes in public health nutrition policies and strategies, diet monitoring, exposure risk assessments, and interventions targeting identified nutritional challenges in particular population groups. Harmonized data are part of the EFSA comprehensive food consumption database
Borrelia lusitaniae and Borrelia valaisiana – potential for causing Lyme borreliosis in Serbia
Get PDFKompleks Borrelia burgdorferi sensu lato trenutno obuhvata dvadest i jednu opisanu vrstu borelija a
karakteriše ih značajna varijabilnost u pogledu geografske distribucije kao i specifičnosti na relaciji
domaćini rezervoari- kompetentni vektor. Poznato je da samo određeni sojevi vrsta borelija izazivaju
bolest kod ljudi. U Severnoj Americi, lajmsku boreliozu uzrokuje samo jedna vrsta borelija-Borrelia
burgdorferi sensu stricto (s.s.), dok u Evropi infekciju kod ljudi može uzrokovati nekoliko različitih vrsta
borelija-Borrelia afzelii, Borrelia garinii, Borrelia bavariensis, Borrelia spielmanii i Borrelia burgdorferi s.s.
Vrste Borrelia valaisiana, Borrelia lusitaniae i Borrelia bissettii identifikovane su samo u pojedinačnim
slučajevima i prepoznate su kao potencijalni patogeni. Različite vrste borelija povezane su sa različitim
kliničkim manifestacijama lajmske borelioze; B. afzelii obično ostaje lokalizovana u koži, B. garinii i
B. bavariensis se obično povezuju s poremećajima nervnog sistema, dok se B. burgdorferi s.s. često
povezuje sa razvojem artritisa. Iako postoje registrovani slučajevi lajmske borelioze u Srbiji, ne postoje
podaci o tome koje vrste borelija izazivaju određene kliničke manifestacije lajmske borelioze.
Region Srbije karakteriše visoka rasprostranjenost i raznovrsnost vrsta borelija u krpeljima i njihovim
domaćinima. Istraživanja prisustva borelija u krpeljima kao i mikrobiološka izolacija sojeva borelija iz
krpelja u Srbiji, ukazala su na dominaciju vrste B. lusitaniae, slede vrste B. afzelii, B. bavariensis, B.
garinii, B. valaisiana i B. burgdorferi s.s. Takođe, B. lusitaniae je detektovana u krpeljima sakupljenim sa
guštera i u uzorcima slezine lisica, dok je B. valaisiana detektovana u krpeljima sakupljenim sa šakala
i ptica. Ispitivanje in vitro osetljivosti lokalnih sojeva borelija (izolovanih iz krpelja vrste Ixodes ricinus
sakupljenih sa vegetacije) na ljudski serum, pokazalo je da su sojevi B. valaisiana otporni na komplement,
dok su određeni sojevi B. lusitaniae (u prisustvu komplementa) podjednako pokretljvi kao i jedini
postojeći soj B. lusitaniae izolovan iz hronične kožne lezije, poreklom iz Portugala. Iako su lokalni sojevi
borelija osetljivi na antibiotike in vitro, ostaje nepoznato koje kliničke manifestacije lajmske borelioze
mogu izazvati vrste B. valaisiana i B. lusitaniae. Potrebno je da se razjasne mehanizami rezistencije
sojeva B. valaisiana i B. lusitaniae (koji cirkulišu u ovoj oblasti) u prisustvu komplementa.The twenty-one described Borrelia species with considerable variability in host and vector associations,
and geographical distribution have been classified to the Borrelia burgdorferi sensu lato complex.
Only a subset of Borrelia species is known to cause human illness. In North America, Lyme borreliosis (LB)
is predominantly caused by the Borrelia burgdorferi sensu stricto (s.s.), while in Europe, the overall
diversity of Borrelia species is higher and LB can be caused by Borrelia afzelii, Borrelia garinii, Borrelia
bavariensis, Borrelia spielmanii, and Borrelia burgdorferi s.s., while Borrelia valaisiana, Borrelia lusitaniae
and Borrelia bissettii have been identified in single cases only and are recognized as potential
pathogens. Different Borrelia species are involved in distinct clinical manifestations of LB; B. afzelii
usually remains localized in the skin, B. garinii and B. bavariensis are usually associated with nervous
system disorders, while B. burgdorferi s.s. is commonly associated with development of the arthritis.
Although there are registered cases of LB in Serbia, there is no data on which Borrelia species cause
certain clinical manifestations of LB. Region of Serbia is characterized by high prevalence and diversity
of Borrelia species in ticks and their vertebrate hosts. The studies on the presence and isolation of Borrelia
from ticks from Serbia pointed to the domination of B. lusitaniae followed by B. afzelii, B. bavariensis,
B. garinii, B. valaisiana and B. burgdorferi s.s. Also, B. lusitaniae was detected in ticks collected
from lizards and in spleen samples collected from red foxes, while B. valaisiana was detected in ticks
collected from golden jackals and birds. In vitro susceptibility of local Borrelia strains isolated from
ticks to human complement, showed B. valaisiana strains resisted complement-mediated killing, while
certain B. lusitaniae strains (in the presence of complement) were equally motile as the only existing
one B. lusitaniae human isolate from Portugal. Although local Borrelia strains are susceptible to antibiotics
in vitro, it remains unknown what clinical manifestations of LB can be caused by B. valaisiana
and B. lusitaniae. It is needed to elucidate the mechanism behind B. valaisiana and B. lusitaniae strains
(circulating in the area) survival in the presence of human complement
Clinical characteristics and management of neurocysticercosis patients: a retrospective assessment of case reports from Europe
No full textObjectives: Neurocysticercosis (NCC) is a parasitic disease caused by the larval stage of the tapeworm Taenia solium. NCC mainly occurs in Africa, Latin America and South-East Asia and can cause a variety of clinical
signs/symptoms. Although it is a rare disease in Europe, it should nonetheless be considered as a differential
diagnosis. The aim of this study was to describe clinical characteristics and management of patients with NCC
diagnosed and treated in Europe.
Methods: We conducted a systematic search of published and unpublished data on patients diagnosed with NCC
in Europe (2000–2019) and extracted demographic, clinical and radiological information on each case, if available. Results: Out of 293 identified NCC cases, 59% of patients presented initially with epileptic seizures (21% focal onset); 52% presented with headache and 54% had other neurological signs/symptoms. The majority of patients had a travel or migration history (76%), mostly from/to Latin America (38%), Africa (32%) or Asia (30%). Treatment varied largely depending on cyst location and number. The outcome was favorable in 90% of the cases.
Conclusions: Management of NCC in Europe varied considerably but often had a good outcome. Travel and
migration to and from areas endemic for T. solium will likely result in continued low prevalence of NCC in Europe.Therefore, training and guidance of clinicians is recommended for optimal patient management
Evolutionary dynamics of Usutu virus: Worldwide dispersal patterns and transmission dynamics in Europe
Get PDFBackground: Usutu virus (USUV) is an emerging mosquito-borne Flavivirus, with birds as the main zoonotic reservoir. Humans are accidental hosts and mostly develop mild or even asymptomatic infections, although severe complications such as encephalitis can also arise. Detailed characterization of the pathogen's phylogenetics may offer valuable insights into the prediction and prevention of potential epidemics; however, lack of uniformity and the number of available USUV sequences worldwide hamper comprehensive investigation. Aim: The study aimed to investigate USUV spatio-temporal dispersal inter- and intracontinentally and to estimate the dynamics of viral spread within Europe. Methods: Phylogeographic and phylodynamic analyses were done using advanced phylogenetic methods implemented in Beast 1.10.4 and Beast 2.6.4 software packages. Results: Herein, we report on a new USUV isolate from Culex pipiens collected in 2019 from Serbia. The results of this research revealed two newly described intercontinental migration events of USUV from Africa to Germany in the 1970s and from Africa to the Middle East (Israel) in the late 90s. Finally, phylodynamic analysis substantiated the ongoing active expansion of USUV in Europe. Conclusion: The data would imply a high potential for further USUV expansion in Europe. Detailed phylogenetic characterization of the pathogen may offer valuable insights into prediction and prevention of potential epidemics; however, lack of uniformity and number of available USUV sequences worldwide hampers comprehensive investigation. This study draws attention to the need for upscaling USUV surveillance
Ekstrakt lista masline u kombinaciji sa Losartanom ima pozitivan efekat na albuminuriju i progresivnu fokalnu segmentalnu glomerulosklerozu u hipertenzivnih miševa: uloga Klotho
No full textPrethodne studije su pokazale da klotho poseduje anti-inflamatornu, antifibrotičku i antioksidativnu ulogu, i da postoji direktna pozitivna korelacija izmedu klotho-a i albuminurije kod nekih animalnih modela hronične bubrežne bolesti (CKD). Fokalno segmentna glomeruloskleroza (FSGS) je oblik CKD, koji se odlikuje prisutnom proteinurijom, hipoalbuminemijom i oksidativnim stresom. Ranije smo pokazali da blokada receptora angiotenzina II tipa 1 losartanom (L) smanjuje proteinuriju, glomerulosklerozu, tubulointersticijsku inflamaciju i fibrozu u animalnom modelu FSGS izazvane adriamicinom (ADR, antitumorski lek) kod spontano hipertenzivnih pacova (SHR), ali ove promene u bubrezima su i dalje bile veće od kontrolnih vrednosti. Ekstrakt lista masline (Olea europaea L.) (OLE), dobro poznat kao prirodni antioksidans, bogat je fenolnim jedinjenjima koja se smatraju odgovornim za snažna antioksidativna i anti-inflamatorna dejstva ekstrakta. Stoga smo ispitivali da li tretman losartanom u kombinaciji sa ekstraktom lista masline može biti efikasniji u usporavanju progresije FSGS. Odrasle ženke SHR su podeljene u četiri grupe. Kontrolni pacovi su primili fiziološki rastvor. SHADR, SHADR+L i SHADR+L+OLE grupe su primile ADR (2 mg/kg telesne mase i.v.) dva puta u intervalu od 3 nedelje. Nakon druge injekcije, SHADR+L i SHADR+L+OLE grupe su primale gavažom L (10 mg/kg/dan), odnosno L+OLE (10+80 mg/kg/dan). Na kraju 6-nedeljnog tretmana analizirali smo albuminuriju, nivo azot monoksida (NO,), 6-nitrotriptofan (marker nitracije proteina), klotho i histopatologiju bubrega. U model grupi uočeno je mačajno povećanje albuminurije i indeksa oitećenja bubrega, ito je bilo praćeno značajno smanjenom ekspresijom klotho proteina i 6-nitortriptofana, kao i nivoa NO, u homogenatu bubrega u poredenju sa ovim vrednostima u kontrolnoj grupi. Tretman losartanom je mačajno smanjio albuminuriju, glomerulosklerozu i tubulointersticijska oštećenja u poredenju sa model grupom, ali su oštećenja bubrega i dalje bila mačajno veća nego u kontrolnoj grupi. Takode, vrednost NO, je vraćena na kontrolni nivo, a proteinska ekspresija 6-nitrotriptofana je mačajno povećana, dok je klotho-a ostala nepromenjena, u poredenju sa model grupom. Interesantno, kada je tretmanu losartanom dodat ekstrakt lista masline primećeno je mačajno i još jače smanjenje albuminurije, glomeruloskleroze, tubulointersticijske inflamacije i fibroze u poredenju sa model grupom. Takode, ovi parametri su sniženi do nivoa koji se nisu mačajno razlikovali od onih u kontroli. Pored toga, ekspresija proteina klotho-a u bubrezima je mačajno povećana u poredenju sa grupama SHADR+L i model Naši rezultati su pokazali da je ekstrakt lista masline kombinovan sa losartanom bio efikasniji od samog tretmana losartanom u usporavanju progresije FSGS kod SHR, a ovaj povoljan efekat uključivao je Klotho signalni put.Previous studies have shown the anti-inflammatory, antifibrotic and antioxidant properties of klotho, and a direct positive correlation between klotho and albuminuria in some chronic kidney disease (CKD) animal models. Focal segmented glomerulosclerosis (FSGS), a form of CKD, is distinguished by proteinuria, hypoalbuminemia, and oxidative stress. We previously showed that blockade of angiotensin Õ type 1 receptor with losartan (L) decreased proteinuria, glomerulosclerosis, tubulointerstitial inflammation, and fibrosis in animal model of FSGS induced by Adriamycin (ADR, anti-cancer agent) in spontaneously hypertensive rats (SHR), but these renal alterations were still higher than control values. Olive (Olea europaea L.) leaf extract (OLE), well-known as natural antioxidant, is rich in phenolic compounds that are thought to be responsible for its powerful antioxidant and anti-inflammatory properties. Here, we examined if losartan treatment in combination with olive leaf extract consumption could be more effective in slowing down the progression of FSGS. Adult female SHRs were divided in four groups. Control rats received vehicle. SHADR, SHADR+L and SHADR+L+OLE groups received ADR (2 mg/kg body weight i.v.) twice in 3-week-interval. After the second injection, SHADR+L, and SHADR+L+OLE groups received by gavage L (10 mg/kg/day), and L+OLE (10+80 mg/kg/day), respectively. At the end of6-week treatment, we analysed albuminuria, renal nitric oxide level (NO,), 6-nitrotryptophan (marker ofnitration of proteins), klotho, and renal histopathology In model group we found significantly increased albuininuria and renal injury score, followed by significantly decreased klotho protein expressions, NOx level, and 6- nitortryptophan in comparison to these values in control group. Losartan treatment significantly reduced albuminuria, glomerulosclerosis, and tubulointerstitial injuries compared to model group, but renal alterations were still significantly higher than in control group. Furthermore, NO, level reversed to control and 6-nitrotryptophan protein expression significantly increased, but klotho remained unchanged, compared to model group. Interestingly, when olive leaf extract was added to losartan treatment, a significant and even stronger decrease of albuminuria, glomerulosclerosis, tubulointerstitial inflammation and fibrosis were observed in comparison to model group. Also, these parameters were lowered to the levels not significantly different than in control. Furthermore, renal protein expression of klotho was significantly increased compared to SHADR+L and model groups. Our results showed that olive leaf extract in addition to losartan treatment was more effective than losartan alone in slowing down the progression of FSGS in SHR, and that beneficial effect involved the klotho signalling pathway
Natural Substances vs. Approved Drugs in the Treatment of Main Cardiovascular Disorders—Is There a Breakthrough?
Get PDFCardiovascular diseases (CVDs) are a group of diseases with a very high rate of morbidity and mortality. The clinical presentation of CVDs can vary from asymptomatic to classic symptoms such as chest pain in patients with myocardial infarction. Current therapeutics for CVDs mainly target disease symptoms. The most common CVDs are coronary artery disease, acute myocardial infarction, atrial fibrillation, chronic heart failure, arterial hypertension, and valvular heart disease. In their treatment, conventional therapies and pharmacological therapies are used. However, the use of herbal medicines in the therapy of these diseases has also been reported in the literature, resulting in a need for critical evaluation of advances related to their use. Therefore, we carried out a narrative review of pharmacological and herbal therapeutic effects reported for these diseases. Data for this comprehensive review were obtained from electronic databases such as MedLine, PubMed, Web of Science, Scopus, and Google Scholar. Conventional therapy requires an individual approach to the patients, as when patients do not respond well, this often causes allergic effects or various other unwanted effects. Nowadays, medicinal plants as therapeutics are frequently used in different parts of the world. Preclinical/clinical pharmacology studies have confirmed that some bioactive compounds may have beneficial therapeutic effects in some common CVDs. The natural products analyzed in this review are promising phytochemicals for adjuvant and complementary drug candidates in CVDs pharmacotherapy, and some of them have already been approved by the FDA. There are insufficient clinical studies to compare the effectiveness of natural products compared to approved therapeutics for the treatment of CVDs. Further long-term studies are needed to accelerate the potential of using natural products for these diseases. Despite this undoubted beneficence on CVDs, there are no strong breakthroughs supporting the implementation of natural products in clinical practice. Nevertheless, they are promising agents in the supplementation and co-therapy of CVDs
Increase in Frequency of Myeloid-Derived Suppressor Cells in the Bone Marrow of Myeloproliferative Neoplasm: Potential Implications in Myelofibrosis
No full textThe Philadelphia-negative myeloproliferative neoplasms (MPNs), defined as clonal disorders of the hematopoietic stem cells, are characterized by the proliferation of mature myeloid cells in the bone marrow and a chronic inflammatory status impacting the initiation, progression, and symptomatology of the malignancies. There are three main entities defined as essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), and genetically classified by JAK2V617F, CALR, or MPL mutations. In MPNs, due to the overproduction of inflammatory cytokines by the neoplastic cells and non-transformed immune cells, chronic inflammation may provoke the generation and expansion of myeloid-derived suppressors cells (MDSCs) that highly influence the adaptive immune response. Although peripheral blood MDSC levels are elevated, their frequency in the bone marrow of MPNs patients is not well elucidated yet. Our results indicated increased levels of total (T)-MDSCs (CD33+HLA-DR−/low) and polymorphonuclear (PMN)-MDSCs (CD33+/HLA-DRlow/CD15+/CD14−) in the bone marrow and peripheral blood of all three types of MPNs malignancies. However, these bone marrow MDSCs-increased frequencies did not correlate with the clinical parameters, such as hepatomegaly, leukocytes, hemoglobin, or platelet levels, or with JAK2 and CALR mutations. Besides, bone marrow MDSCs, from ET, PV, and PMF patients, exhibited immunosuppressive function, determined as T-cell proliferation inhibition. Notably, the highest T-MDSCs and PMN-MDSC levels were found in PMF samples, and the increased MDSCs frequency strongly correlated with the degree of myelofibrosis. Thus, these data together indicate that the immunosuppressive MDSCs population is increased in the bone marrow of MPNs patients and may be implicated in generating a fibrotic microenvironment