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Metabolic profiling of CD19+ cells in chronic lymphocytic leukemia by single-cell mass spectrometry imaging
No full textThis dataset contains data used in CD19+ lymphocyte metabolome research. The research was carried out as part of the research project called "Leukocyte Metabolic Markers in Chronic Lymphocytic Leukemia Spatially Resolved by the Imaging Mass Spectrometry (acronym CLLaIMS) financed by the Croatian Science Foundation (grant IP-2022-8228).
The dataset consists of excel worksheets with raw data of m/z signal intensity.The data was collected using single-cell MALDI-TOF Mass Spectrometry Imaging in a sample of 10 subjects. This research was conducted at the Clinical Institute for Laboratory Diagnostics in cooperation with the Clinical Institute for Transfusion Medicine and the Department of Hematology of University Hospital Center Osijek, Croatia from February 2022 to January 2024
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No full textLeukocitni metabolički biljezi u kriničnoj limfocitnoj leukemiji prostorno razlučeni slikovnom spektrometrijom masaLeukocyte Metabolic Markers in Chronic Lymphocytic Leukemia Spatially Resloved by the Imaging Mass Spectrometr
Promoter Methylation Status of ASC/TMS1/PYCARD is Associated with Decreased Overall Survival and TNM Status in Patients with Early Stage Non-small Cell Lung Cancer (NSCLC).
No full textBACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide, with 5-year overall survival less than 15%. Therefore, it is essential to find biomarkers for early detection and prognosis. Aberrant DNA methylation is a common feature of human cancers and its utility is already recognized in cancer management. The aim of this study was to explore the diagnostic and prognostic value of the promoter methylation status of the ASC/TMS1/PYCARD and MyD88 genes, key adaptor molecules in the activation of the innate immune response and apoptosis pathways.
METHODS: A total of 50 non-small cell lung cancer (NSCLC) patients were enrolled in the study. Methylation of bisulphite converted DNA was quantified by pyrosequencing in fresh frozen malignant tissues and adjacent non-malignant tissues. Associations between methylation and lung function, tumor grade and overall survival were evaluated using receiver-operating characteristics (ROC) analysis and statistical tests of hypothesis.
RESULTS: Methylation level of tested genes is generally low but significantly decreased in tumor tissues (ASC/TMS1/PYCARD, P<0.0001; MyD88, P<0.0002), which correlates with increased protein expression. Three CpG sites were identified as promising diagnostic marker candidates; CpG11 (-63 position) in ASC/TMS1/PYCARD and CpG1 (-253 position) and 2 (-265 position) in MyD88. The association study showed that the methylation status of the ASC/TMS1 CpG4 site (-34 position) in malignant and non-malignant tissues is associated with the overall survival (P=0.019) and the methylation status of CpG8 site (-92 position) is associated with TNM-stage (P=0.011).
CONCLUSIONS: The methylation status of the ASC/TMS1/PYCARD and MyD88 promoters are promising prognostic biomarker candidates. However, presented results should be considered as a preliminary and should be confirmed on the larger number of the samples
Targeting Burkitt Lymphoma with a Tumor Cell-specific Heptamethine Carbocyanine-cisplatin Conjugate
No full textBACKGROUND: Burkitt lymphoma is a fast-growing mature B cell malignancy, whose genetic hallmark is translocation and activation of the c-myc gene. Prompt multiagent immunochemotherapy regimens can have favorable outcomes, but prognosis is poor in refractory or relapsed disease. We previously identified a novel family of near-infrared heptamethine carbocyanine fluorescent dyes (HMCD or DZ) with tumor-homing properties via organic anion-transporting peptides. These membrane carriers have uptake in tumor cells but not normal cells in cell culture, mouse and dog tumor models, patient-derived xenografts, and perfused kidney cancers in human patients.
METHODS: Here we report the cytotoxic effects of a synthesized conjugate of DZ with cisplatin (CIS) on B cell lymphoma CA46, Daudi, Namalwa, Raji, and Ramos cell lines in cell culture and in xenograft tumor formation. Impaired mitochondrial membrane permeability was examined as the mechanism of DZ-CIS-induced lymphoma cell death.
RESULTS: The new conjugate, DZ-CIS, is cytotoxic against Burkitt lymphoma cell lines and tumor models. DZ-CIS retains tumor-homing properties to mitochondrial and lysosomal compartments, does not accumulate in normal cells and tissues, and has no nephrotoxicity in mice. DZ-CIS accumulated in Burkitt lymphoma cells and tumors induces apoptosis and retards tumor cell growth in culture and xenograft tumor growth in mice.
CONCLUSION: DZ-CIS downregulated c-myc and overcame CIS resistance in myc-driven TP53-mutated aggressive B cell Burkitt lymphoma. We propose that DZ-CIS could be used to treat relapsed/refractory aggressive Burkitt lymphomas
Short-Term High-NaCl Dietary Intake Changes Leukocyte Expression of VLA-4, LFA-1, and Mac-1 Integrins in Both Healthy Humans and Sprague-Dawley Rats: a Comparative Study
No full textThis study is aimed at assessing the effects of a short-term high-salt (HS) diet on the peripheral blood leukocyte (PBL) activation status in healthy rats and young human individuals. Distribution of PBL subpopulations and surface expression of integrins were determined using flow cytometry in 36 men and women on a 7-day low-salt diet (<3.2 g salt/day) immediately followed by a 7-day HS diet (~14 g salt/day) or in Sprague-Dawley (SD) rats (n = 24) on a 0.4% NaCl diet (aLS group) or a 4% NaCl diet (aHS group) for 7 days. The aHS group presented with an increased frequency of granulocytes, while the frequency of lymphocytes was reduced. Although in humans HS diet reduced the expression of CD11b(act) integrin on lymphocytes, the frequency of CD11b(act)-bearing cells among all PBL subsets was increased. The aHS group of rats exhibited increased expression of total CD11b/c in granulocytes and CD3 lymphocytes. The expression of CD11a was significantly reduced in all PBL subsets from human subjects and increased in the aHS group. CD49d expression on all PBL subsets was significantly decreased in both humans and rats. In human subjects, we found reduced frequencies of intermediate monocytes accompanied by a reciprocal increase in classical monocytes. Present results suggest that a short-term HS diet can alter leukocytes' activation status and promote vascular low-grade inflammation
Impact of High Salt Diet on Cerebral Vascular Function and Stroke in Tff3-/-/C57BL/6N Knockout and WT (C57BL/6N) Control Mice
No full textHigh salt (HS) dietary intake leads to impaired vascular endothelium-dependent responses to various physiological stimuli, some of which are mediated by arachidonic acid (AA) metabolites. Transgenic Tff3-/- gene knockout mice (Tff3-/-/C57BL/6N) have changes in lipid metabolism which may affect vascular function and outcomes of stroke. We aimed to study the effects of one week of HS diet (4% NaCl) on vascular function and stroke induced by transient occlusion of middle cerebral artery in Tff3-/- and wild type (WT/C57BL/6N) mice. Flow-induced dilation (FID) of carotid artery was reduced in WT-HS mice, but not affected in Tff3-/--HS mice. Nitric oxide (NO) mediated FID. NO production was decreased with HS diet. On the contrary, acetylcholine-induced dilation was significantly decreased in Tff3-/- mice on both diets and WT-HS mice. HS intake and Tff3 gene depletion affected the structural components of the vessels. Proteomic analysis revealed a significant effect of Tff3 gene deficiency on HS diet-induced changes in neuronal structural proteins and acute innate immune response proteins' expression and Tff3 depletion, but HS diet did not increase the stroke volume, which is related to proteome modification and upregulation of genes involved mainly in cellular antioxidative defense. In conclusion, Tff3 depletion seems to partially impair vascular function and worsen the outcomes of stroke, which is moderately affected by HS diet
Treatment of Trigeminal Neuralgia by Radiofrequency Neuromodulation
No full textTrigeminalna neuralgija (TN) jedan je od najčešćih uzroka boli lica. Medikamentno liječenje katkada nije dovoljno učinkovitoi može imati neprihvatljive nuspojave. Ostale mogućnosti liječenja obuhvaćaju kiruški zahvat, te minimalno invazivne tehnike poput perkutane rizotomije glicerolom, perkutane mikrokompresije balonom, te kontinuirane radiofrekventne termokoagulacije (CRF). CRF se široko rabi u liječenju TN, no visoke temperature >70° C mogu dovesti do ozbiljnih komplikacija, dok suniže temperature nedovoljno učinkovite. Pulsna radiofrekventna neuromodulacija (PRF) rabi struju u kratkim, visokovoltažnim impulsima, dok “tiha” faza omogućava eliminaciju topline te temperatura tkiva u pravilu ne prelazi 42° C. Mehanizam kojim se PRF dovodi do smanjenja boli bez termičkog oštećenja tkiva nije potpuno razjašnjen, no pretpostavlja se da brze promjene električnog polja dovode do promijenjenog prijenosa bolnih impulsa. Prema dostupnoj literaturi, u odnosu na CRF učinkovitost je nešto niža, no sa značajno manje komplikacija. Ipak, produljenje vremena izvođenja PRF sa 2 na 6 do 8 minuta može značajno povećati učinkovitost navedene metode.Trigeminal neuralgia (TN) is one of the most common causes of facial pain. Sometimes medical treatment is not effective enough and may have unacceptable side effects. Other treatment options include surgical interventions and minimally invasive techniques such as percutaneous rhizotomy with glycerol, percutaneous balloon decompression, and percutaneous radiofrequency thermocoagulation (CRF). CRF is widely used for TN treatment, but high temperatures >70 °C can cause serious complications, while lower temperatures are inefficient. Pulsed radiofrequency (PRF) uses the current in short, high-power pulses, while the ‘silent’ phase allows heat elimination and temperature of the tissue generally does not exceed 42 °C. The mechanism by which PRF leads to pain reduction without thermal damage to the tissue is not fully understood, but rapid changes in the electrical fi eld are assumed to result in altered transmission of pain signals. According to available literature, compared to CRF, effi cacy is lower, but with signifi cantly less complications. However, the prolongation of PRF time from 2 to 6 to 8 minutes can signifi cantly increase the effi ciency of this method
Spinal Cord Stimulation for the Treatment of Chronic Pain – The Initial Osijek Experience
No full textStimulacija kralježnične moždine (engl. spinal cord stimulation - SCS) je postupak kojim se ugrađuju jedna ili dvije elektrode u epiduralni prostor torakalne i lumbalne kralježnice te se elektrode spoje na bateriju koja isporučuje stimulaciju programiranu za tog bolesnika. SCS je indiciran kod bolesnika s jakom kroničnom boli koja se ne smanjuje primjenom ostalih oblika liječenja. Ovaj zahvat se radi kod bolesnika koji imaju bolove u lumbalnom dijelu kralježnice nakon neurokirurških zahvata na lumbalnoj kralježnici s posljedičnim stvaranjem priraslica, sa širenjem boli u donje ekstremitete ili bez širenja boli, kod bolesnika s bolovima nakon amputacije donjih ekstremiteta, te boli koja je posljedica kompleksnih regionalnih bolnih sindroma. U KBC-u Osijek tijekom 2017. g. postupak perkutane ugradnje elektroda za stimulator kralježnične moždine učinjen je kod 5 bolesnika. Prema našim saznanjima sve dosadašnje ugradnje stimulatora kralježnične moždine u Republici Hrvatskoj učinjene su kirurškim, a ne perkutanim pristupom. Bolesnike se procjenjivalo putem numeričke ljestvice za procjenu boli, Oswestry upitnika za procjenu stupnja invalidnosti, SF-36 upitnika za procjenu kvalitete života. Upitnici su ispunjavani prije zahvata, na kontrolnom pregledu prije ugradnje trajne stimulacije, te mjesec i tri mjeseca nakon ugradnje trajnog stimulatora. U ukupnim vrijednostima opaženo je značajno poboljšanje ocjene tjelesnog zdravlja, smanjenje stupnja invalidnosti kao i trenutni, prosječni i najjači intenzitet boli proteklih četiri tjedana u odnosu na prvu vizitu.Spinal cord stimulation (SCS) is a procedure of incorporating one or two electrodes into the epidural space of the thoracic and lumbar spine. The epidural space is located above the dura that covers the spinal cord. This procedure is performed in patients with pain in the lumbar spine with or without pain spreading to lower extremities, in patients with lower extremity amputation, and pain resulting from complex regional pain syndromes. SCS is indicated in patients with severe chronic pain that cannot be alleviated by other modes of treatment. Total SCS was performed in fi ve patients. Patients fi lled out a numerical scale assessing the intensity of pain, the Oswestry questionnaire assessing the degree of disability, and the SF36 questionnaire assessing the quality of life. The above-mentioned questionnaires were completed by the patients before implantation of permanent SCS, then one month after permanent SCS and 3 months of permanent SCS. The results showed signifi cant improvement in the quality of life at the 4th visit in almost all SF-36 items except for limiting the activity for physical health, emotional problems, and mental health. In the overall values, the improvement in physical health assessment with a median 33 (interquartile range from 30 to 59) was signifi cantly better as compared to the 15 (interquartile range from 11 to 16) on the fi rst visit (Friedman’s test, p=0.007). There was also a signifi cant reduction in the degree of disability, as well as in the current, average and most severe pain intensity lasting for four weeks compared to the fi rst visit
Serum Levels of the High-mobility Group box 1 Protein (HMGB1) in Children with Type 1 Diabetes Mellitus: Case-control Study
No full textINTRODUCTION: The involvement of the high-mobility group box 1 protein (HMGB1) in various autoimmune and inflammatory diseases has been documented; however, the role of this proinflammatory molecule in children with diabetes type 1 (T1DM) has not been addressed. The aim of this case-control study is to compare the serum level of HMGB1 in children with newly diagnosed T1DM (group 1) and a control group composed of healthy children.
MATERIAL AND METHODS: This case-control study included 136 children: group 1 (n = 96) and a control group (n = 40). Measurements were taken from serum for the following: HMGB1, white blood cell count, C-reactive protein, glucose, haemoglobin A1C, and β-cell autoantibodies (GADA-65, IA-2, ICA). HMGB1 was determined using enzyme-linked immunosorbent assay on a Labsystems iEMS Reader MF analyser (Labsystems Diagnostics Oy, Helsinki, Finland).
RESULTS: The level (median and interquartile range) of HMGB1 was statistically higher (p < 0.001) in children with T1DM: 8.7 (5.0-9.8) µg/l, in comparison with the control group: 1.0 (0.6-1.4) µg/l. No correlation was found between HMGB1 and HbA1c in group 1, or between HMGB1 and BMI. A statistically higher percentage of positive children for autoantibodies were present in group 1 compared to the control group (p ≤ 0.001). HMGB1 serum levels were also tested and the presence of autoantibodies, and none of those antibodies correlated with the level of HMGB1.
CONCLUSIONS: The higher level of HMGB1 in children with T1DM, compared to the control group, indicates that this proinflammatory molecule is a good candidate marker of inflammation in children with T1DM
Nutritional Considerations of Cardiovascular Diseases and Treatments
No full textNutritional considerations of many chronic diseases are not fully understood or taken into consideration in everyday clinical practice. Therefore, it is not surprising that high proportion of hospitalized patients with cardiovascular diseases remains underdiagnosed with malnutrition. Malnourished patients have increased risk of poor clinical outcomes, complications rate, prolonged hospital stay, more frequent rehospitalizations, and lower quality of life. The purpose of this review is to recapitulate recent data on nutritional considerations in cardiovascular medicine