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.
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.
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).
Cervical cancer (CC) is a complex, multistep process involving various viral, molecular, cellular, endogenous, and environmental events that transform normal cervical epithelium into a malignant tumor through a cascade of events. The contribution of high-risk human papillomavirus (HPV) to cancer is significant but involves many additional mechanisms such as oxidative stress (OS), arrested apoptosis of non-functional intraepithelial neoplastic cells, senescence-associated secretory phenotype (SASP), and the final epithelial–mesenchymal transition (EMT) of cervical epithelial neoplasia (CIN) cells. While high-risk HPV oncoproteins E6 and E7 are widely recognized as the primary triggers of CC, the critical role of E6 in degrading the p53 regulatory protein, thereby inhibiting the apoptosis of reactive oxygen species (ROS)-damaged neoplastic cells, is frequently underappreciated in the gynecological literature. Arrested apoptosis of non-functional neoplastic intraepithelial cells is a key event in cervical carcinogenesis and the biological basis of CIN progression via SASP senescence and ultimately EMT. While recent reviews touched upon each of the reviewed aspects, this review aims to provide a general understanding of all links in this complex molecular-biological chain, from HPV infection, oxidative stress, arrested apoptosis, SASP, and EMT. Beyond providing an encompassing primer for clinical researchers, we additionally review potential oxidative stress-related markers for shifting the classic diagnostic and therapeutic paradigms of CIN and cervical cancer.
Background/Objectives: Nurses’ job satisfaction is influenced by organizational conditions and psychological responses to demanding work. Although perceived organizational support, organizational justice, and burnout are established correlates of nurses’ work outcomes, less is known about how distributive justice and emotional exhaustion may operate simultaneously within the association between organizational support and job satisfaction. This study examined these two theoretically distinct indirect pathways. Methods: A cross-sectional study was conducted among 157 nurses employed at General County Hospital Požega, Croatia, between November 2023 and January 2025. Perceived organizational support, distributive justice, emotional exhaustion, and job satisfaction were assessed using standardized questionnaires. Structural equation modeling used robust maximum likelihood estimation with full information maximum likelihood for partially missing data; indirect associations were evaluated in a separate maximum-likelihood model using 5000 bootstrap samples. Results: Greater perceived organizational support was associated with more favorable perceptions of distributive justice and lower emotional exhaustion. Greater distributive justice was associated with higher job satisfaction, whereas emotional exhaustion was associated with lower job satisfaction. The remaining direct association between organizational support and job satisfaction was not statistically significant after both pathways were included. Bootstrap analyses supported indirect associations through both distributive justice and emotional exhaustion. A sensitivity analysis showed that reversing the ordering of distributive justice and organizational support yielded identical global fit indices. Conclusions: Organizational support, perceived fairness, and emotional exhaustion appear to be closely interconnected aspects of nurses’ work experience. The findings integrate organizational and psychological perspectives and identify supportive management, fair resource allocation, and the prevention of emotional exhaustion as complementary organizational targets. Because of the cross-sectional design, the pathways should be interpreted as statistical indirect associations rather than causal mechanisms.
Background/Objectives: Ego defense mechanisms are subconscious processes that help individuals cope with stressors from both external and internal realities. They are divided into three levels based on their adaptive function. Patients undergoing chronic hemodialysis are those who have been treated with this method for longer than three months. Only a few studies have examined the defense mechanisms in hemodialysis patients. Our study aimed to examine the association between ego defense mechanisms and alexithymia, depression, and sleep disorders, as well as clinical and biochemical variables, in a group of 170 hemodialysis patients. Methods: We used the Defense Style Questionnaire-40, the Toronto Alexithymia Scale-26, the Pittsburgh Sleep Quality Index, and the Hamilton Depression Inventory as our analyses methods. Clinical and biochemical variables, along with interdialytic weight gain, were measured before the hemodialysis session. Results: There was a positive correlation between the affect displacement and dissociation with leukocyte levels (Spearman’s rho = 0.192, p = 0.02; rho = 0.165, p = 0.04), and between autistic fantasy and phosphorus levels (rho = −0.163, p = 0.04). Depressive HD patients had higher levels of somatization, affect displacement, and splitting compared to the HD patients without depression (Man–Whitney U test, p = 0.005, p = 0.022, p = 0.045). There were higher levels of immature defense mechanisms in the group of patients with alexithymia than in the group without alexithymia (Mann–Whitney U test, p < 0.001). Conclusions: The immature defense mechanisms were our research model’s strongest predictive factor of alexithymia (OR = 1.87, 95% CI 1.27 to 2.75).