Type 2 diabetes is a disease that causes numerous complications disrupting the functioning of the entire body. Therefore, new treatments for the disease are being sought. Studies in recent years have shown that forkhead box O (FOXO) proteins may be a promising target for diabetes therapy. FOXO proteins are transcription factors involved in numerous physiological processes and in various pathological conditions, including cardiovascular diseases and diabetes. Their roles include regulating the cell cycle, DNA repair, influencing apoptosis, glucose metabolism, autophagy processes and ageing. FOXO1 is an important regulator of pancreatic beta-cell function affecting pancreatic beta cells under conditions of insulin resistance. FOXO1 also protects beta cells from damage resulting from oxidative stress associated with glucose and lipid overload. FOXO has been shown to affect a number of processes involved in the development of diabetes and its complications. FOXO regulates pancreatic β-cell function during metabolic stress and also plays an important role in regulating wound healing. Therefore, the pharmacological regulation of FOXO proteins is a promising approach to developing treatments for many diseases, including diabetes mellitus. In this review, we describe the role of FOXO proteins in the pathogenesis of diabetes and the role of the modulation of FOXO function in the therapy of this disease.
Ovarian cancer (OC) is one of the biggest problems in gynecological oncology and is one of the most lethal cancers in women worldwide. Most patients with OC are diagnosed at an advanced stage; therefore, there is an urgent need to find new biomarkers for this disease. Gene expression profiling is proving to be a very effective tool for exploring new molecular markers for OC patients, although the relationship between such markers and patient survival and clinical outcomes is still elusive. Moreover, polymorphisms in genes encoding both apoptosis-associated proteins and oncoproteins may serve as key markers of cancer susceptibility. The aim of our study was to analyze the polymorphisms and expressions of the BCL2, BAX and c-MYC genes in a group of 198 women, including 98 with OC. The polymorphisms and mRNA expressions of the BCL2, BAX and c-MYC genes were analyzed using real-time PCR. The analysis of the BAX (rs4645878; G>A) and c-MYC (rs4645943; C>T) polymorphisms showed no association with ovarian cancer risk. The BCL2 polymorphism (rs2279115; C>A) showed a significant difference in the frequency of genotypes between the studied groups (CC: 23.47% vs. 16.00%, AA: 25.51% vs. 37.00%; p = 0.046; OR = 1.61). Furthermore, the expression levels of the BCL2 and c-MYC genes showed a decrease at the transcript level for OC patients compared to the control group (BCL2: 17.46% ± 3.26 vs. 100% ± 8.32; p < 0.05; c-MYC: 37.56% ± 8.16 vs. 100% ± 9.12; p < 0.05). No significant changes in the mRNA level were observed for the BAX gene (104.36% ± 9.26 vs. 100% ± 9.44; p > 0.05). A similar relationship was demonstrated in the case of the protein expressions of the studied genes. These findings suggest that the CC genotype and C allele of the BCL2 polymorphism could be genetic risk factors for OC development. A gene expression analysis indicated that BCL2 and c-MYC are associated with OC risk.
Increasing knowledge of the gut microbiota and its interference in human homeostasis in recent years has contributed to a better understanding of number of different interactions occurring in the gastrointestinal tract. Disruption of the microbiota is detrimental to health and contributes to the development of numerous diseases and may also be an accelerator of pathophysiological processes such as atherosclerosis. Cardiovascular diseases are the most common cause of death worldwide, so the development of new methods to support the treatment and prevention of these diseases becoms one of the priorities of modern medicine. Probiotics may constitute an important element of support in the treatment and prevention of CVD (cardiovascular diseases). A number of papers support such a statement, however, larger clinical trials are needed. Through a number of mechanisms including mitigating inflammation, sealing the intestinal epithelium, and affecting metabolism, probiotics may have a beneficial effect on general health and slow down the pathogenesis of many diseases, including those affecting the cardiovascular system. This article contains a review of current discoveries on the role of probiotics in the prevention and support of CVD treatment.
Osteoporosis is a multifactorial and polygenic disease caused by an imbalance between osteoclastogenesis and osteoblastogenesis, leading to a decrease in bone mineral density and the occurrence of disorders in the microarchitecture and metabolism of bone tissue. In postmenopausal women, there is a significant decrease in the production of estrogens, which play a key role in maintaining proper bone mineral density. Estrogens have an inhibitory effect on the development and activity of osteoclasts by reducing the synthesis of pro-resorption cytokines and stimulating the expression of osteoprotegerin (OPG). Osteoprotegerin is a cytokine that prevents bone loss by inhibiting the process of osteoclastogenesis, reducing bone resorption. The aim of our study was to determine the influence of the rs3102735 (−163A>G), rs3134070 (−245T>G), rs207361 (−950T>C), rs7844539 (6890A>C), and rs2073618 (1181G>C) polymorphisms of the OPG gene on the risk of osteoporosis and osteopenia in postmenopausal Polish women. The study included 802 unrelated women (osteoporosis: n = 317, osteopenia: n = 110, controls: n = 375) at postmenopausal age (54.7 ± 8.6 years). Genetic analysis was performed using real-time PCR. BMD values as well as clinical and bone parameters with the tested polymorphisms were analyzed among the study population. Analysis of the PPARG rs1801282 variants did not show any association with the risk of osteoporosis and osteopenia. However, for the OPG rs207361 polymorphism, we observed a statistically significant association with the risk of osteoporosis, suggesting that the OPG rs207361 variant may be one of the genetic markers associated with the pathogenesis of osteoporosis.
Rhabdomyosarcoma of the cervix is a soft tissue sarcoma that usually occurs in young women. It is very rare in adulthood. We discuss symptoms, the process of diagnosis of rhabdomyosarcoma embryonale of the cervix in a 61-year-old women and differences in treatment dependent on patient’s age. A 61-year-old woman with symptoms such as palpable mass in the external cervical opening and post-menopausal hemorrhaging was admitted to the oncology ward where excision of the polyp was performed. Embryonal rhabdomyosarcoma (ERMS) was diagnosed by histopathological examination of obtained tissues. The diagnosis was complemented by chest computed tomography and pelvis magnetic resonance imaging to exclude metastases. A Wertheim–Meigs operation and excision of the ovaries, the fallopian tubes and the surrounding tissue was performed in the course of treatment. In the patient’s follow-up of 25 months to date, there have been no signs of recurrence or symptoms connected to ERMS. Based on the therapeutic outcome, the decision to limit the treatment to a surgical resection was adequate for a post-menopausal patient. Because of the rarity of ERMS in the post-menopausal age, we think that the patient should be carefully followed up to further examine this issue and develop diagnostic and treatment guidelines.
Summary: The human microbiota has a tremendous effect on our health. In the last decades, our knowledge about interactions between bacteria and humans have grown greatly. Not only is it necessary for humans to synthesize vitamins, to have tight intestinal barriers or protect from pathogens, it also has an impact on our immune system and thus plays an important role in autoimmune diseases and prevention of excessive inflammatory response. The idea of probiotics is to restore the balance in humans digestive microbiota. There is a growing number of scientific papers that proves a positive impact of using probiotics in various diseases. However, there are still questions that need to be answered before probiotics play a bigger role in the treatment. This paper presents the information about the use of probiotics in most common diseases of gastrointestinal tract.