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The potential of single-walled carbon nanotube-based therapeutic platforms targeting astrocytes
No full textCultivatable Bacteriota of Chronic Wound of Patients with Diabetic Foot Syndrome with Critical Limb Ischemia Based on Wound Biopsy in Peri-Revascularization Period
No full textDiabetic foot syndrome is often associated with inflammation. The aim of this study was to evaluate the impact of improved blood supply on the change in the clinical status and culturable bacteriota of chronic wounds. Patients with diabetic foot and peripheral arterial disease with a Rutherford score of 5 or 6 were included (n = 23). The blood supply to the limb was assessed with laboratory tests and two time-point qualitative cultures using a wound biopsy. The baseline parameters of the blood supply to the limb were Transcutaneous Oxygen Perfusion (TCPO2) of 15.0 mmHg, an Ankle Brachial Index (ABI) of 0.7, and a Toe Brachial Index (TBI) of 0.1, with an average Wound, Infection, Inflammation (WIfI) score of 5.7 (high). The most frequently isolated pathogens were Staphylococcus aureus (26.1%), followed by the Enterobacteriaceae family and Pseudomonas spp. (13.0%, each). Negative cultures were present in 47.8% (n = 11). The control parameters of blood supply improved; TCPO2 was 38.5 mmHg, the ABI was 0.9, and the TBI was 0.3, with a reduction in the average WIfI score to 3.7 (mild), while total colony-forming units (CFUs) increased by 13.5%. No cases of reocclusion or restenosis were observed during the study; however, small amputations were performed in two patients (8.7%). Five (21.7%) ulcers were significantly reduced and two (8.7%) progressed, while a negative culture at follow-up was obtained in five fewer patients than at baseline and nine patients presented growth despite having an initial negative result. Quantitative reduction was obtained in four (17.4%) cases. Pathogen distribution at follow-up resembled baseline findings. Optimizing clinical environments (enhancing blood flow and controlling inflammation) in general over focusing singularly on microbiota composition or revascularization seems to be crucial and arguably outweighed the impact of microbial change alone; in particular, reperfusion may increase the conditions to bacterial growth at the first stage
Intestinal Microbiota Modulation by Fecal Microbiota Transplantation in Nonalcoholic Fatty Liver Disease
No full textNumerous factors are involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which are responsible for its development and progression as an independent entity, but also thanks to their simultaneous action. This is explained by the hypothesis of multiple parallel hits. These factors are insulin resistance, lipid metabolism alteration, oxidative stress, endoplasmic reticulum stress, inflammatory cytokine liberation, gut microbiota dysbiosis or gut–liver axis activation. This is a systematic review which has an aim to show the connection between intestinal microbiota and the role of its disbalance in the development of NAFLD. The gut microbiota is made from a wide spectrum of microorganisms that has a systemic impact on human health, with a well-documented role in digestion, energy metabolism, the stimulation of the immune system, synthesis of essential nutrients, etc. It has been shown that dysbiosis is associated with all three stages of chronic liver disease. Thus, the modulation of the gut microbiota has attracted research interest as a novel therapeutic approach for the management of NAFLD patients. The modification of microbiota can be achieved by substantial diet modification and the application of probiotics or prebiotics, while the most radical effects are observed by fecal microbiota transplantation (FMT). Given the results of FMT in the context of metabolic syndrome (MetS) and NAFLD in animal models and scarce pilot studies on humans, FMT seems to be a promising treatment option that could reverse intestinal dysbiosis and thereby influence the course of NAFLD
Statistically correlated disordered freeform random metasurfaces: generation and electromagnetic numerical simulation
No full textWe present a method for generating and performing full-wave simulations of statistically correlated disordered freeform random metasurfaces (SC-DFRM). The SC-DFRM represents a specific type of disordered metasurface in which randomness is not entirely independent but follows certain statistical correlation rules. In generating these metasurfaces, we investigate both Gaussian and exponential power spectral densities. The domain decomposition spectral method is successfully used to analyze the impact of correlation lengths on the contributions of both coherent and incoherent fields to the total averaged scattered intensity
Contribution of Sorting Nexin 3 in the Cytomegalovirus Assembly
No full textBackground/Objectives: Cytomegalovirus (CMV) infection expands early endosomes (EEs) into tubular extensions that may contribute to the control of virus replication and virion assembly. Sequential recruitment of protein coats and sorting nexins (SNXs) creates membrane zones at the EEs that serve as scaffolds for membrane tubulation and retrieval of cargo proteins, including host cell signaling proteins and viral glycoproteins. This study aims to investigate whether the SNX3-dependent zone of EEs contributes to CMV replication and assembly. Methods: Protein localization was analyzed by confocal imaging and expression by Western blot. The contribution of SNX3 to murine CMV (MCMV) replication, assembly compartment (AC) formation, and virion release was analyzed by siRNA and shRNA depletion. The impact of other downstream SNXs that act in EE tubulation was investigated by combined siRNA knockdowns of SNX1, SNX2, SNX4, SNX17, and SNX27 on cell lines expressing shRNA for SNX3. Results: The SNX3-162 isoform acting at EEs was efficiently knocked down by siRNA and shRNA. The SNX3-dependent EE zone recruited SNX27 and contributed to Rab10-dependent tubulation within the pre-AC. SNX3 was not essential for MCMV replication but contributed to the SNX27-, SNX17- and SNX4-dependent release of virions. Silencing SNX3 further reduced the release of virions after silencing SNX27, SNX4, and SNX17, three SNXs that control recycling to the plasma membrane. Conclusions: SNX3 contributes to the formation of pre-AC and MCMV assembly. It acts sequentially with SNX27, SNX4, and SNX17 along the recycling pathway in the process of the production and release of infection virions, suggesting that multiple membrane sources may contribute to the secondary envelopment of MCMV virions
CAUSAL VARIANTS OF THALASSEMIA SYNDROMES IN THE POPULATION OF THE CROATIAN LITTORAL AND ISTRIA
No full textCilj istraživanja: Istražiti uzročne varijante talasemijskih sindroma u populaciji Hrvatskog
primorja i Istre te ih usporediti s uzročnim varijantama u drugim populacijama. Specifični
ciljevi su ispitati hematološke, biokemijske i kliničke značajke u pojedinaca s talasemijskim
sindromima, utvrditi korelaciju genotipa i fenotipa te izraditi algoritam za molekularno
genetičku dijagnostiku talasemija.
Materijal i metode: U presječno istraživanje je uključeno 112 ispitanika iz 65 obitelji koje nisu
u međusobnom krvnom srodstvu sa sumnjom na talasemiju. Analizirani su hematološki i
biokemijski parametri. Molekularno-genetička analiza globinskih gena provedena je metodama
lančane reakcije polimerazom i sekvenciranja po Sangeru. Procjena težine talasemijskog
fenotipa je učinjena Mahidol sustavom bodovanja. U statističkoj obradi podataka korišten je
Mann-Whitney U-test.
Rezultati: Heterozigotni β-talasemijski sindrom je otkriven u 30 ispitanika i njihovih 16 prvih
srodnika u 24 obitelji iz Hrvatskog primorja i Istre koje nisu u međusobnom krvnom srodstvu.
U svih ispitanika utvrđena je mikrocitoza i hipokromija, a u 60,0% i blaga anemija. Hemoglobin
(Hb) F je bio povišen u 75,0%, a HbA2 u 60,7% ispitanika. Specifični genotipski profil u
populaciji Hrvatskog primorja i Istre čini devet uzročnih varijanti, od kojih na pet varijanti
otpada 83,2%: Hb Lepore Boston-Washington (BW), β+ IVS-I-110, β0 IVS-II-1, β0 IVS-I-1 i β+
IVS-I-6. Najčešće uzročne varijante su pretežito mediteranskog podrijetla i većinom se
podudaraju s varijantama opisanim u susjednim populacijama Mediterana i Balkana. Nisu
otkrivene nove varijante. Svi ispitanici su imali blagi oblik talasemije. Postoji dobra korelacija
genotipa i fenotipa. U ispitanika s istim genotipom i varijabilnim biokemijskim fenotipom (HbF
>5%) otkrivena je prisutnost XmnI polimorfizma, kao potencijalnog sekundarnog
modifikatora. Niti jedan ispitanik nije bio nositelj α-talasemijske varijante.
Zaključak: Molekularno-genetičko testiranje ima sve veći značaj u postavljanju precizne
dijagnoze talasemijskih sindroma, otkrivanju statusa nositelja, genetičkom savjetovanju, izradi
preventivnih programa, definiranju terapijskih ciljeva i razvoju javnozdravstvenih mjera.
Vrijedno je nastaviti istraživanja na molekularnoj karakterizaciji uzročnih varijanti β
talasemijskih sindroma na području cijele Hrvatske.Objectives: To investigate the causal variants of thalassemia syndromes in the population of the
Croatian Littoral and Istria, and compare the findings with other populations. The specific aims
are to analyze the hematological, biochemical, and clinical features in individuals with
thalassemia syndromes, to determine the correlation between genotype and phenotype, and to
design the algorithm for molecular-genetic diagnosis of thalassemia.
Material and Methods: The cross-sectional study included 112 participants from 65 unrelated
families with suspected thalassemia. Hematological and biochemical parameters were
analyzed. Molecular-genetic analysis of the globin genes was performed using polymerase
chain reaction and Sanger sequencing. The assessment of thalassemic phenotype was performed
according to Mahidol scoring system. The Mann-Whitney U-test was used for statistical data
processing.
Results: Heterozygous β-thalassemia syndrome was identified in 30 participants and their 16
first-degree relatives from 24 unrelated families from the Croatian Littoral and Istria.
Microcytosis and hypochromia were observed in all subjects, with mild anemia present in 60%.
Hemoglobin (Hb) F was elevated in 75,0%, and HbA2 in 60,7% of subjects. The specific
genotype profile in the population of the Croatian Littoral and Istria consists of nine causal
variants, five of which account for 83.2%: Hb Lepore Boston-Washington (BW), β+ IVS-I-110,
β0 IVS-II-1, β0 IVS-I-1, and β+ IVS-I-6. The most frequent causal variants are predominantly
of Mediterranean origin and largely overlap with variants reported in neighboring
Mediterranean and Balkan populations. No new variants were detected. All participants had a
mild type of disease. There is a good correlation between genotype and phenotype. In subjects
with the same genotype and a variable biochemical phenotype (HbF >5%), the presence of the
XmnI polymorphism was detected as a potential secondary modifier. None α-thalassemia
carrier was identified.
Conclusion: Molecular-genetic testing is increasingly important for the precise diagnosis of
thalassemia syndromes, detection of carriers, genetic counseling, the development of preventive
strategies, setting therapeutic goals, and the implementation of public health programs. It is
worth to continue research on the molecular characterization of causal variants of β-thalassemia
syndromes in the Croatian population
Neuronal-ILC2 interactions regulate pancreatic glucagon and glucose homeostasis
No full textThe immune system shapes body metabolism, while interactions between peripheral neurons and immune cells control tissue homeostasis and immunity. However, whether peripheral neuroimmune interactions orchestrate endocrine system functions remains unexplored. After fasting, mice lacking type 2 innate lymphoid cells (ILC2s) displayed disrupted glucose homeostasis, impaired pancreatic glucagon secretion, and inefficient hepatic gluconeogenesis. Additionally, intestinal ILC2s were found in the pancreas, which was dependent on their expression of the adrenergic beta 2 receptor. Targeted activation of catecholaminergic intestinal neurons promoted the accumulation of ILC2s in the pancreas. Our work provides evidence that immune cells can be regulated by neuronal signals in response to fasting, activating an inter-organ communication route that promotes pancreatic endocrine function and regulation of blood glucose level
Influence of a Zombie-like State of the Liver on Drugs and Its Medico-Legal Implications: A Scoping Review
No full textWhen cells remain permanently trapped in a particular cell cycle stage, they are in senescence. This also occurs in the liver. Such cells are often referred to as “zombie cells”, and an entire organ filled with these “zombie cells” is said to be in a “zombie-like” state, characterized by a lack of function. The senescence-associated secretory phenotype (SASP) encompasses the substances these “zombie cells” release, which can significantly affect nearby cells and tissues. While cellular senescence and SASP are related concepts, they are distinct. This scoping review aims to clarify the role of hepatocyte senescence and hepatocyte SASP in the administration of pharmaceuticals, as well as their relevance to medico-legal practice, disability claims, and insurance coverage. In this context, the effects of pharmaceuticals on senescent hepatocytes are discussed, particularly regarding the medico-legal implications of substances likely to be abused. In conclusion, hepatocyte senescence may be relevant in clinical or medico-legal work because it sheds a new light on interpreting clinical findings and expert witness statements
Oestrogenic and androgenic activity of oxybenzone and methylparaben in vitro
No full textMotivated by emerging concerns about health hazards associated with various industrial chemicals, this study investigated the disruption of endocrine system using well established in vitro assays. Due to the lack of scientific data on adverse effects of chemicals used in personal care products (PCPs), the focus was placed on oestrogenic and androgenic action of photostabiliser oxybenzone and preservative methylparaben. To this end we relied on in vitro assays for oestrogen and androgen receptor activation based on HeLa-9903 and AREcoScreen GR KO M1 cell lines to determine dose response according to respective OECD Test Guidelines 455 and 458. Our findings clearly demonstrate that both chemicals act as oestrogen receptor agonists and androgen receptor antagonists, raising additional concerns about health risks for humans posed by excessive and widespread use of such chemicals in PCPs
Silicon-Mediated Modulation of Olive Leaf Phytochemistry: Genotype-Specific and Stress-Dependent Responses
No full textSecondary metabolites in olive (Olea europaea L.) leaves constitute a complex framework wherein phenylpropanoids, terpenoids, and secoiridoids in particular, serve as major contributors to olive plant resilience. Silicon (Si) stands as a mediator of defense mechanisms in plants, enhancing their protective responses and adaptability. A field trial on one-year-old plantlets of two metabolically distinct olive genotypes was conducted to investigate the effects of foliar-applied Si on the phytochemical profiles of locally treated leaves. Silicon’s systemic effects in juvenile leaves were also appraised. We accounted for intervarietal differences in nutrient uptake and conducted in situ measurements of physiological indices. The peak of the summer season and the onset of autumn were chosen as the two sampling time points. Intense summer conditions prompted metabolic adjustments that resulted in phytochemical profiles unique to each cultivar. These profiles were further significantly altered by Si while remaining genotype-specific, with substantial increases in prominent compounds like oleuropein (105% and 252%) and verbascoside (62% and 126%), depending on the genotype. As the pressure from environmental factors eased, the differences in Si-mediated phytochemical responses emerged. Silicon had a limited effect on the phytochemical profile of the resilient cultivar which acquired a metabolic steady-state, while it significantly altered the profile of its metabolically more versatile counterpart, resulting with a progressive increase in its oleuropein (37%) and verbascoside (26%) levels. These effects extended to untreated, juvenile leaves as well. While effective in altering and improving the phytochemical composition of olive leaves, Si acted in a manner that adhered to each genotype’s metabolic foundation. The intensity of environmental constraints, along with each cultivar’s inherent sensitivity to them, seems to be tied to silicon’s capacity to mediate significant phytochemical alterations. The extent of silicon’s prophylactic function may therefore be dependent on a genotype’s metabolic foundation and overall sensitivity, and as such it seems inseparable from stress and its intensity