Effect of Metformin and Simvastatin in Inhibiting Proadipogenic Transcription Factors.

Obesity is a multifactorial chronic disease characterized by the excessive accumulation of fat in adipose tissue driven by hypertrophy and hyperplasia of adipocytes through adipogenesis. Adipogenesis plays a key role in the development of obesity and related metabolic disorders, which makes it potential target for the therapeutic approach to obesity. An increasing number of studies confirm the pleiotropic action of the combined treatment with metformin and statins, suggesting their anti-hypertensive, anti-inflammatory, and anti-adipogenic effect. The aim of this study was to analyze the effect of different doses of metformin (MET) and simvastatin (SIM) on the expression of key transcription factors of adipogenesis. Mouse 3T3-L1 preadipocytes were induced to differentiation in adipogenic medium with sustained MET and SIM treatment to assess the effect on adipogenesis. Nine days after initiating adipogenesis, the cells were prepared for further experiments, including Oil Red O staining, RT-PCR, Western blotting, and immunocytochemistry. Treating the cells with the combination of MET and SIM slightly reduced the intensity of Oil Red O staining compared with the control group, and down-regulated mRNA and protein expression of PPARγ, C/EBPα, and SREBP-1C. In conclusion, the inhibitory effect of MET and SIM on adipocyte differentiation, as indicated by decreased lipid accumulation, appears to be mediated through the down-regulation of adipogenic transcription factors, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding pro-tein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP-1C).

Association of intestinal inflammation and permeability markers with clinical manifestations of Parkinson's disease.

INTRODUCTION: Intestinal inflammation and gut microbiota dysbiosis can stimulate degeneration of dopaminergic neurons and development of Parkinson's disease (PD) via the gut-brain axis in certain patients. METHODS: In a case-control study, fecal markers of intestinal inflammation and permeability were measured using the ELISA method in PD patients and healthy controls. Motor and nonmotor symptoms were assessed using the Movement Disorder Society (MDS) Unified PD Rating Scale, Hoehn & Yahr scale, MDS Non-Motor Symptom Scale, Scales for Outcomes in PD - Autonomic Dysfunction, PD Sleep Scale - 2, Montreal Cognitive Assessment, Beck Anxiety Inventory, and Beck Depression Inventory-II. A correlation was established between the intestinal inflammation and permeability markers and PD symptoms. RESULTS: Higher levels of beta-defensin 2, zonulin and lactoferrin were recorded in PD patients compared to controls. Calprotectin and secretory immunoglobulin A showed no significant differences. Regression analysis indicated the roles of beta-defensin 2 and lactoferrin in predicting PD likelihood. Calprotectin yielded positive correlations with disease duration, depression, motor fluctuations, and gastrointestinal symptoms; beta defensin 2 with thermoregulation; and secretory immunoglobulin A with depression. Secretory immunoglobulin A showed negative correlation with age and age at disease onset, while zonulin showed negative correlation with the MDS Unified PD Rating Scale total score. CONCLUSIONS: Fecal markers differed in PD patients compared to controls and correlated with age, disease duration, and some nonmotor symptoms. Future studies should identify the subgroups of PD patients that are likely to develop intestinal inflammation.

The Importance of Prediabetes Screening in the Prevention of Cardiovascular Disease.

Background: Prediabetes is a disordered state of glucose metabolism defined by an elevated blood glucose level that is below the level required for the diagnosis of diabetes. Prediabetes is associated with an increased risk of cardiovascular disease. The onset and progression of macrovascular disease occur during the prediabetes phase. Early diagnosis and screening of prediabetes are essential steps to prevent diabetes and its associated complications. Objective: To assess the prevalence of prediabetes and undiagnosed diabetes in patients with cardiovascular disease according to the ADA criteria. Methods: This cross-sectional study included 2968 a high cardiovascular risk patients aged 40 to 75 years admitted to the Department of Internal Medicine. Sociodemographic variables and other relevant medical history information were collected by the researchers during the clinical interview. A fasting blood sample was obtained to determine HbA1c levels and other relevant laboratory findings. Results: Of the total number of participants, 1496 participants were not diagnosed with diabetes, 485 (32.4%) of them had HbA1c values indicating prediabetes and 158 (10.6%) of them had HbA1c values indicating new diagnosed diabetes. Up to one-third of those with undiagnosed prediabetes had already been diagnosed with cardiovascular complications. Conclusion: Routine screening of glycemic metabolism could be valuable in identifying high-risk individuals before a cardiovascular event occurs.

Unlocking the Potential of Mesenchymal Stem Cells in Gynecology: Where Are We Now?

Stem cells, with their remarkable capacity for differentiation into diverse cell types, are vital for the development as well as maintenance of health and homeostasis. Two unique abilities set them apart from other cells: self-renewal and the capacity for differentiation. They play important roles in embryogenesis, development, regeneration, and various other processes. Over the last decade, there has been increased interest in their potential use in the treatment of numerous diseases and disorders across multiple fields of medicine in acute, chronic, innate, and acquired diseases. Stem cells are key to maintaining the body's homeostasis and regulating growth and tissue functions. There are several types of stem cells-embryonic, adult, and human-induced pluripotent cells. Currently, mesenchymal stem cells are of great interest due to their regenerative, immunomodulatory, analgesic, and antimicrobial (anti-inflammatory) effects. Recent studies have shown the potent regenerative effect of stem cell therapy in gynecologic diseases such as infertility, Asherman syndrome, lichen sclerosus, polycystic ovary syndrome, premature ovarian insufficiency, genitourinary syndrome of menopause, and rectovaginal fistulas. Moreover, the successful isolation of oogonial stem cells could lead to a revolution in the field of gynecology and the potential treatment of the conditions discussed. This review aims to provide a better understanding of the latest therapeutic options involving stem cells and raise awareness of this promising yet not widely known topic in gynecology and medicine in general.

Mechanistic-Based Classification of Endocytosis-Related Inhibitors: Does It Aid in Assigning Drugs against SARS-CoV-2?

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) canonically utilizes clathrin-mediated endocytosis (CME) and several other endocytic mechanisms to invade airway epithelial cells. Endocytic inhibitors, particularly those targeting CME-related proteins, have been identified as promising antiviral drugs. Currently, these inhibitors are ambiguously classified as chemical, pharmaceutical, or natural inhibitors. However, their varying mechanisms may suggest a more realistic classification system. Herein, we present a new mechanistic-based classification of endocytosis inhibitors, in which they are segregated among four distinct classes including: (i) inhibitors that disrupt endocytosis-related protein-protein interactions, and assembly or dissociation of complexes; (ii) inhibitors of large dynamin GTPase and/or kinase/phosphatase activities associated with endocytosis; (iii) inhibitors that modulate the structure of subcellular components, especially the plasma membrane, and actin; and (iv) inhibitors that cause physiological or metabolic alterations in the endocytosis niche. Excluding antiviral drugs designed to halt SARS-CoV-2 replication, other drugs, either FDA-approved or suggested through basic research, could be systematically assigned to one of these classes. We observed that many anti-SARS-CoV-2 drugs could be included either in class III or IV as they interfere with the structural or physiological integrity of subcellular components, respectively. This perspective may contribute to our understanding of the relative efficacy of endocytosis-related inhibitors and support the optimization of their individual or combined antiviral potential against SARS-CoV-2. However, their selectivity, combined effects, and possible interactions with non-endocytic cellular targets need more clarification.

Adipogenesis as a Potential Anti-Obesity Target: A Review of Pharmacological Treatment and Natural Products.

Obesity is recognized as a severe threat to overall human health and is associated with type 2 diabetes mellitus, dyslipidemia, hypertension, and cardiovascular diseases. Abnormal expansion of white adipose tissue involves increasing the existing adipocytes' cell size or increasing the number through the differentiation of new adipocytes. Adipogenesis is a process of proliferation and differentiation of adipocyte precursor cells in mature adipocytes. As a key process in determining the number of adipocytes, it is a possible therapeutic approach for obesity. Therefore, it is necessary to identify the molecular mechanisms involved in adipogenesis that could serve as suitable therapeutic targets. Reducing bodyweight is regarded as a major health benefit. Limited efficacy and possible side effects and drug interactions of available anti-obesity treatment highlight a constant need for finding novel efficient and safe anti-obesity ingredients. Numerous studies have recently investigated the inhibitory effects of natural products on adipocyte differentiation and lipid accumulation. Possible anti-obesity effects of natural products include the induction of apoptosis, cell-cycle arrest or delayed progression, and interference with transcription factor cascade or intracellular signaling pathways during the early phase of adipogenesis.

Increased bone mineral density in postmenopausal women with type 2 diabetes mellitus.

BACKGROUND AND OBJECTIVES: Studies of bone mineral density (BMD) in women with type 2 diabetes mellitus have shown conflicting results. We conducted this study to determine whether postmenopausal women with diabetes have higher BMD than non-diabetic women of similar age, and to investigate the relationship between BMD and relevant clinical characteristics in these groups of women. PATIENTS AND METHODS: We retrospectively analyzed lumbar spine, femoral neck, and radius BMD data and other relevant clinical data for 130 postmenopausal women with type 2 diabetes mellitus and 166 non-diabetic women collected during a voluntary screening for osteoporosis in postmenopausal women without a history of low bone mass or osteoporotic fractures. RESULTS: Women with type 2 diabetes mellitus had significantly higher mean lumbar spine BMD ( 0.903+/-0.165 vs. 0.824+/-0.199, respectively, P<.001) and mean femoral neck BMD (0.870+/-0.132 vs. 0.832+/-0.134, respectively, P<.05) than non-diabetic women. In both groups of women, age correlated negatively with BMD levels at all three anatomical sites. Higher body mass index was associated only with higher lumbar spine BMD in both groups. Alkaline phosphatase levels showed a negative correlation with BMD at all sites in women with type 2 diabetes mellitus. CONCLUSION: Postmenopausal women with type 2 diabetes mellitus have higher BMD levels than non-diabetic women with similar clinical characteristics, and require a more scrutinized approach in managing low bone mass.

The role of oral glucose intolerance test in reducing pregnancy complications.

The influence of glucose monitoring during pregnancy on newborn body weight, and complications during pregnancy and labor was assessed. We performed a retrospective analysis of macrosomal children, fetal growth, caesarean sections, malformations, still-births and the number of oral glucose tolerance test (OGTT) carried out in a five-year period. The proportion of women participating in OGTT tests increased from 20% to 40% (p<0.05) between 2000 and 2004. Gestation diabetes mellitus (GDM) proportions among pregnant women seen at the Department of Obstetrics and Gynecology at Slavonski Brod General Hospital, Croatia increased from 1% to 6.7% (p < 0. 05) during the observed period. Proportion of births identified as macrosomal decreased from 13.3% to 12.2% (p<0.05). Additionally, infant mortality and still-births along with other fetal and maternal complications declined during the same period. These results suggest that regular measurements of glucose tolerance during pregnancy may prevent preterm birth, decrease the proportion of macrosomal newborns, lower mortality and decrease fetal and maternal complication incidence during pregnancy and delivery.

Effects of raloxifene on changes in bone density.

Raloxifene hydrochloride therapy effectiveness in bone mineral density (BMD) changes compared to calcium and vitamin D3 therapy over a 2-year period. Case-control study: a group of 254 women was prescribed raloxifene (raloxifene hydrochloride) together with calcium and vitamin D3 while other group of 254 women used calcium and vitamin D3 therapy. BMD was measured at the hip, spine and forearm at the beginning and at the end of the 2-year period. Treatment with raloxifene resulted in a 3.7% increase in BMD at the spine in 98% of examinees. A 1.2% BMD increase was shown in 75% of examinees at the hip. A 1.2% decrease in BMD at forearm shown in 93% of examinees using raloxifene. The calcium and vitamin D3 therapy led to an increase in BMD in 58% examinees at the spine, in 56% at the hip and in 38% at the forearm, which was significantly lower than in women using raloxifene. Among women using calcium and vitamin D alone an average BMD decrease of 1.2% was registered on 42% of examinees at the spine, 2.6% decrease on 46% of examinees at the hip and 4.2% decrease on 35% of examinees at the forearm. Treatment with raloxifene resulted in a significant increase in BMD at the spine with odds ratio (OR 5.85, p <0.05) compared with calcium and vitamin D3 alone. There was no statistically proven increase in BMD at either the hip (OR 0.015) or forearm (OR 0.122).

[Midwives in Brod na Savi (Croatia) in 19th century]. / O primaljama u Brodu na Savi u XIX. stoljecu.

The development of population policy and health legislation as a result of government, the need for more young, healthy, working and military active population, resulted in the education of all health workers including midwives, legal regulation of their work, increasing their number and training of midwifery profession. With the development of this profession conditions of women giving birth, pregnancy and birth control were gradually improved, and thus influenced the birth rate and mortality of the population and the natural growth. On the example of the town of Brod na Savi one can see that it was time-consuming and controlled development of the midwifery profession in the region, which have affected the poor socio-economic conditions, poor climatic conditions, and the presence of the border and the consequent large-scale migration of the population. It is important to note that the foundations for population policies and the observed midwifery profession enabled the development of the same in the coming period.