Search

Background/Aim. Good metabolic control can delay the onset and progression of chronic complications of diabetes mellitus (DM). Intensified insulin therapy (IIT) is the cornerstone of good metabolic control in the treatment of type 1 DM (T1DM) while avoiding hypoglycemia and body weight (BW) gain in those patients. The aim of the study was to assess the effects of IIT with insulin analogs (aspart and glargine) in T1DM patients. Methods. This prospective clinical study included 49 patients with at least one year of T1DM duration, who were on IIT with human insulin at that moment. They commenced therapy with insulin aspart for three months, followed by insulin glargine for another three months. An analysis of blood glucose (BG) control (glycated hemoglobin – HbA1c, mean BG, fasting BG, postprandial BG, and glycemic variability) and analysis of BW, hypoglycemia, and C-reactive protein (CRP) levels were performed. Results. The HbA1c level decreased slightly (non-significantly) after three months of insulin aspart therapy (from 9.28% to 8.83%) and decreased significantly after the aspart/glargine combination (to 8.08%; p < 0.001). After the first three months with aspart therapy, a significant reduction in postprandial BG was noted after all three main meals. The mean postprandial rise of BG was significantly reduced. The variability of daily BG was significantly reduced (standard deviation of BG fell from 2.28 mmol/L to 1.90 mmol/L; p < 0.05). The mean BG value in the profiles decreased (from 9.11 mmol/L to 8.31 mmol/L; p < 0.05). All BG values in the profiles after six months were statistically significantly lower compared to the initial values, as well as the mean BG (6.88 mmol/L; p < 0.001) and the variability of daily BG (1.49 mmol/L; p < 0.01). Our results showed a significant reduction in the number of hypoglycemias after three months, especially after the introduction of insulin glargine therapy (significant reduction in the number of symptomatic, asymptomatic, and nocturnal hypoglycemias). The results showed a discrete but significant reduction in BW and a significant reduction in CRP levels (from 3.43 mg/L to 2.25 mg/L; p < 0.001). Conclusion. Treatment of patients with T1DM with insulin analogs (insulin aspart and insulin glargine) in IIT leads to improved BG control with a reduction in the number of hypoglycemia, BW, and CRP levels.

Our review paper evaluates the impact of plant-based products, primarily derived from plants from Serbia, on P-glycoprotein (P-gp) activity and their potential in modulating drug resistance in cancer therapy. We focus on the role and regulation of P-gp in cellular physiology and its significance in addressing multidrug resistance in cancer therapy. Additionally, we discuss the modulation of P-gp activity by 55 natural product drugs, including derivatives for some of them, based on our team's research findings since 2011. Specifically, we prospect into sesquiterpenoids from the genera Artemisia, Curcuma, Ferula, Inula, Petasites, and Celastrus; diterpenoids from the genera Salvia and Euphorbia; chalcones from the genera Piper, Glycyrrhiza, Cullen, Artemisia, and Humulus; riccardins from the genera Lunularia, Monoclea, Dumortiera, Plagiochila, and Primula; and diarylheptanoids from the genera Alnus and Curcuma. Through comprehensive analysis, we aim to highlight the potential of natural products mainly identified in plants from Serbia in influencing P-gp activity and overcoming drug resistance in cancer therapy, while also providing insights into future perspectives in this field. [ABSTRACT FROM AUTHOR]

The field of oncology has witnessed remarkable progress in personalized cancer therapy. Functional precision medicine has emerged as a promising avenue for achieving superior treatment outcomes by integrating omics profiling and sensitivity testing of patient-derived cancer cells. This review paper provides an in-depth analysis of the evolution of cancer-directed drugs, resistance mechanisms, and the role of functional precision medicine platforms in revolutionizing individualized treatment strategies. Using two-dimensional (2D) and three-dimensional (3D) cell cultures, patient-derived xenograft (PDX) models, and advanced functional assays has significantly improved our understanding of tumor behavior and drug response. This progress will lead to identifying more effective treatments for more patients. Considering the limited eligibility of patients based on a genome-targeted approach for receiving targeted therapy, functional precision medicine provides unprecedented opportunities for customizing medical interventions according to individual patient traits and individual drug responses. This review delineates the current landscape, explores limitations, and presents future perspectives to inspire ongoing advancements in functional precision medicine for personalized cancer therapy. [ABSTRACT FROM AUTHOR]

In the previous study fifteen jatrophane diterpenes were isolated from the Euphorbia nicaeensis latex. Fourteen of them have been shown to be potent P-glycoprotein (P-gp) inhibitor in two MDR cancer cells (NCI-H460/R and DLD1-TxR). The aim of this study was to determine whether and which jatrophane diterpenes can be isolated from the root of the plant, and then to examine their inhibition power on P-glycoprotein of selected cancer cell lines (NCI- -H460, DLD1, U87, NCI-H460/R, DLD1-TxR and U87-TxR). Two previously undescribed jatrophane diterpenes were isolated from the root of E. nicaeensis collected in Deliblato Sand (Serbia). The structures of the isolated compounds were determined using 1D and 2D NMR, as well as HRESIMS data. The results obtained by MTT assay showed different antitumor potential of these two jatrophanes. Compound 1 inhibited cell growth of non-small cell lung carcinoma cell lines NCI-H460 and NCI-H460/R, as well as glioblastoma cell lines U87 and U87-TxR, while jatrophane 2 was almost completely inactive in the suppression of cancer cell growth in a given range of concentrations. The obtained results also showed that the isolated compounds have an inhibitory effect on P-glycoprotein, as well as that their inhibitory potential is similar.

This article is an editorial that discusses the potential of natural products and nanoparticles in cancer treatment. It highlights the challenges faced in utilizing natural products for medicinal purposes, such as poor solubility and bioavailability. Nanoparticles, on the other hand, offer unique properties that allow for precise targeting of tumors and reduced impact on healthy tissues. The article also mentions specific studies that explore the application of nanoparticles in targeted therapy for different types of cancer. Overall, the article emphasizes the need for further research in this field to enhance the effectiveness of cancer treatments. [Extracted from the article]

Background: C-Myc is one of the major cellular oncogenes overexpressed in non-small cell lung carcinoma (NSCLC). Its deregulated expression is necessary but not sufficient for malignant transformation. We evaluated expression of MYC gene in NSCLC patients and its association with alterations in the genes previously identified to be related to NSCLC pathogenesis, PHACt R 3 and E2F4. Methods: We analyzed M YC gene expression by qRT-PCR in 30 NSCLC patients' samples and paired normal lung tissue. M YC expression was further statistically evaluated in relation to histopathological parameters, PHACTR3 and E2F4 gene alterations and survival. Alterations in aforementioned genes were previously detected and identified based on AP-PCR profiles of paired normal and tumor DNA samples, selection of DNA bands with altered mobility in tumor samples and their characterization by the reamplification, cloning and sequencing. Results: M YC s significantly increased in NSCLC samples and its overexpression significantly associated with squamous cell carcinoma subtype. Most importantly, MYC overexpression significantly coincided with mutations in PHACTR3 and E2F4 genes, in group of all patients and in squamous cell carcinoma subtype. Moreover, patients with jointly overexpressed M YC and altered PHACTR3 or E2F4 showed trend of shorter survival. Conclusions: Overall, MYC is frequently overexpressed in NSCLC and it is associated with mutated PHACTR3 gene, as well as mutated E2F4 gene. These joint gene alterations could be considered as potential molecular markers of NSCLC and its specific subtypes.

Introduction/Objective. Intensive oxidative stress is proven in patients with diabetes mellitus and important in the development of a microvascular complication of type 2 diabetes mellitus. The aim of the study was to investigate the relationship between morphometric parameters of retinal blood vessels in patients with diabetic retinopathy (DR) and the levels of parameters of oxidative stress: advanced oxidation protein product (AOPP), thiobarbituric acid reactive substances (TBARS), and total sulfhydryl (SH) groups in blood samples. Methods. The patients (the group with DR and controls) were sex- and age-matched. Glycaemia, hemoglobin A1C HbA1C, total cholesterol and its fractions, and triglycerides were measured in blood samples. AOPP and total SH groups were determined in the plasma by specific methods. Modification of the thiobarbituric acid method was used for the determination of TBARS. The number and diameter of retinal blood vessels, as morphometric parameters on digital retinal photography, was determined by using the ImageJ software. Student’s t-test was used as the statistical method for the evaluation of differences between the morphometric and blood test parameters. The significance of differences in morphometric parameters of retinal blood was establish by one-way ANOVA. Results. Significantly higher levels of parameters of oxidative stress (AOPP and TBARS) were in the group of patients with DR than in the controls. This difference was also present among the patients with mild and severe forms of DR (AOPP F 77.03, p < 0.001) (TBARS F 63.28, p < 0.001). The diameter of retinal blood vessels correlated with levels of AOPP, but only in patients with mild DR. Conclusion. Parameters of oxidative stress, AOPP and TBARS, may be important for the follow-up of DR. In early stages in diabetic retinopathy, AOPP can be a valuable biomarker.

Introduction/Aim. Adrenal incidentalomas (AIs) are defined as tumours revealed during imaging procedures of abdomen or abdominal laparotomy, performed in patients without previous suspicion for adrenal disease. This study was conducted to evaluate morphological and functional features of AIs seven years after the initial diagnosis. Patients and Thirty-eight AI patients were monitored for seven years, with CT scans used for morphological follow-up. Hormonal activity assessments included basal cortisol levels, adrenocorticotropic hormone, overnight dexamethasone suppression test, plasma or urinary metanephrines, vanillymandelic acid, electrolytes, hematocrit, acid-base status, oral glucose tolerance test, and chromogranin A. Results. Functional activity was confirmed in six patients, with mild autonomous cortisol secretion (MACS) detected in two patients. Nine patients underwent adrenalectomy. Histopathological examination revealed hormonal activity in six cases, adrenocortical carcinoma was found in one patient, while secondary deposits from bronchial carcinoma were detected in one patient. Among the remaining 29 patients observed for the first year, tumor size remained stable. After seven years, two patients experienced tumor enlargement = 1 cm, along with the development of MACS on endocrine evaluation. Adrenalectomy was recommended for one patient due to tumor size exceeding 4 cm. Conclusion. The initial adrenal incidentaloma (AI) evaluation must include comprehensive diagnostic procedures for surgical consideration. Subsequent follow-up should include CT imaging after 12 months to monitor the tumor growth. Although mild autonomous cortisol secretion does not tend to progress to overt Cushing's syndrome, it can develop in patients initially considered to have hormonally inactive tumor. Our findings suggest that even small adrenal masses (< 4 cm) can enlarge over seven years, potentially evolving into MACS. Therefore, regular long-term monitoring every 5 - 7 years is recommended. [ABSTRACT FROM AUTHOR]

Background/Aim. The value of ultrasound in functional disorders can be significant. That is why the question arises on the use of ultrasound examination of thyroid gland and its echogenicity as a screening method in early detection of disfunctions, of the gland primarily subclinical and clinical forms of hypothyreoidism. The objective of this paper was to determine antibodies of thyroid peroxidase (anti-TPO) and thyroglobuline antibodies (anti-TG) increase frequency in relation to the character of ultrasound echogenicity as well as to estimate the frequency of subclinically and clinically obvious hypothyreoidism in relation to the changed echogenicity. Methods. Study included 656 patients in outpatient clinic during 2014. All examinees underwent ultrasound examination of thyroid gland, the blood was taken for determination of free thyroxine (FT4), thyroidstimulating hormone (TSH), anti-TPO and anti-TG. The patients were divided into two groups; the group A with normal echogenicity of thyroid gland tissue, and the group B with decreased echogenicity. The group B was divided into two subgroups, B1 with a mildly decreased and B2 with significantly decreased echogenicity. Results. TPO antibody, TSH and TG antibody positivity and their mean values in the group B were significantly higher, as well as in subgroups B1 and B2, in relation to the group A (p < 0.001). In the group A, only 4 (1%) examinees were indicated with subclinical hypothyreoidism. In the group B, the sublinical hypothyreoidism was indicated in 42, while the clinical hypothyreoidism was indicated in 16 examinees. Fifty-eight (25%) examinees suffered from thyroid gland altered function. In the subgroup B1, 16 examinees were indicated with subclinical and 4 with clinical hypothyreoidism. Twenty (11%) examinees suffered from altered thyroid function. In the group B2, the subclinical hypothyreoidism was found in 26 examinees, while the clinical hypothyreoidism was found in 12. Thirty-eight (76%) examinees suffered from altered thyroid function. Conclusion. The ultrasound screening of thyroid gland plays an important role in early detection of thyroid disfunction, i.e., sublinical and clinical hypothyreoidism. Decreased ultrasound echogenicity represents the significant marker of altered thyroid gland function. In these persons we have determined the high percentage of subclinical and clinical hypothyreoidism frequency.

In this paper, the synthesis of fourteen alkylamino and arylamino derivatives of sesquiterpene quinone avarone and its model compound tert-butylquinone is described. Branched, cyclic, allylic and benzylic alkylamino/arylamino groups were introduced into the quinone moiety. For all the obtained derivatives, their biological activity and redox properties were studied. The cytotoxic activity of the synthesized derivatives towards multidrug resistant (MDR) human non-small cell lung carcinoma NCI-H460/R cells, their sensitive counterpart NCI-H460 and human normal keratinocytes (HaCaT) was investigated. The antimicrobial activity towards Gram-positive and Gram-negative bacteria, and fungal cultures was determined. Some of the synthesized derivatives showed selectivity for cancer cells, including MDR cells. Regarding their cell death induction potential, the most promising compounds were allylamino derivatives, preferentially triggering apoptosis, with high selectivity for cancer cells, including MDR cells. Several compounds showed promising antimicrobial activity, comparable to those of commercial antibiotic and antimycotic agents.