Can Ashwagandha Benefit the Endocrine System?-A Review.

Withania somnifera, also known as Ashwagandha, has been used in traditional medicine for thousands of years. Due to the wide range of its activities, there has been interest in its possible beneficial effects on the human body. It is proved that, among others, Ashwagandha has anti-stress, anti-inflammatory, antimicrobial, anti-cancer, anti-diabetic, anti-obesity, cardioprotective, and hypolipidemic properties. Particularly interesting are its properties reported in the field of psychiatry and neurology: in Alzheimer's disease, Parkinson's disease, multiple sclerosis, depression, bipolar disorder, insomnia, anxiety disorders and many others. The aim of this review is to find and summarize the effect that Ashwagandha root extract has on the endocrine system and hormones. The multitude of active substances and the wide hormonal problems faced by modern society sparked our interest in the topic of Ashwagandha's impact on this system. In this work, we also attempted to draw conclusions as to whether W. somnifera can help normalize the functions of the human endocrine system in the future. The search mainly included research published in the years 2010-2023. The results of the research show that Ashwagandha can have a positive effect on the functioning of the endocrine system, including improving the secretory function of the thyroid gland, normalizing adrenal activity, and multidirectional improvement on functioning of the reproductive system. The main mechanism of action in the latter appears to be based on the hypothalamus-pituitary-adrenal (HPA) axis, as a decrease in cortisol levels and an increase in hormones such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in men were found, which results in stress level reduction and improvement in fertility. In turn, other studies prove that active substances from W. somnifera, acting on the body, cause an increase in the secretion of triiodothyronine (T3) and thyroxine (T4) by the thyroid gland and a subsequent decrease in the level of thyroid-stimulating hormone (TSH) in accordance with the hypothalamus-pituitary-thyroid (HPT) axis. In light of these findings, it is clear that Ashwagandha holds significant promise as a natural remedy for various health concerns, especially those related to the endocrine system. Future research may provide new insights into its mechanisms of action and expand its applications in both traditional and modern medicine. The safety and toxicity of Ashwagandha also remain important issues, which may affect its potential use in specific patient groups.

The Association between Acetabulum Fractures and Subsequent Coxarthrosis in a Cohort of 77 Patients-A Retrospective Analysis of Predictors for Secondary Hip Osteoarthritis.

OBJECTIVE: the aim of this study was to document the occurrence of THA after acetabulum surgery and examine the factors that predict its occurrence. METHODS: This study included 77 consecutive patients who were admitted for acetabulum fracture surgery between 2012 and 2019. The inclusion criteria were acetabular fractures and indications for operative management. The exclusion criteria were acetabular fractures treated non-operatively, fractures requiring primary THA, and periprosthetic acetabular fractures. Data concerning demographics, date of injury, date of surgery, surgical approach, stabilization, and further reconstructive surgery were collected retrospectively. The number of patients who underwent THA and their risk factors were recorded. The minimum follow-up for each patient was 2 years of observation. A total of 77 patients with a mean age of 53 years were included. RESULTS: At a mean follow-up of 2 years, THA was performed in 16 (20.8%) patients due to post-traumatic arthritis. An analysis of the surgical approaches showed that the Kocher-Langenbeck approach increased the risk of THA nearly 12 times compared with the ilioinguinal approach (p = 0.016). Furthermore, the duration of the waiting period for surgery significantly impacted the occurrence of THA, with each additional day leading to an 89% increase in the risk of prosthesis usage (p = 0.001). CONCLUSIONS: This study suggests that acetabular fractures may lead to post-traumatic hip osteoarthritis. The surgical approach and the waiting time for surgery are potential factors that may predict secondary hip osteoarthritis and the need for subsequent THA. However, further investigations should be performed to establish predictors for secondary hip osteoarthritis, and especially to determine the impact of the surgical approach.

Natural Phytochemicals as SIRT Activators-Focus on Potential Biochemical Mechanisms.

Sirtuins are a family of proteins with enzymatic activity. There are seven mammalian sirtuins (SIRT1-SIRT7) that are found in different cellular compartments. They are a part of crucial cellular pathways and are regulated by many factors, such as chemicals, environmental stress, and phytochemicals. Several in vitro and in vivo studies have presented their involvement in anti-inflammatory, antioxidant, and antiapoptotic processes. Recent findings imply that phytochemicals such as resveratrol, curcumin, quercetin, fisetin, berberine, and kaempferol may regulate the activity of sirtuins. Resveratrol mainly activates SIRT1 and indirectly activates AMPK. Curcumin influences mainly SIRT1 and SIRT3, but its activity is broad, and many pathways in different cells are affected. Quercetin mainly modulates SIRT1, which triggers antioxidant and antiapoptotic responses. Fisetin, through SIRT1 regulation, modifies lipid metabolism and anti-inflammatory processes. Berberine has a wide spectrum of effects and a significant impact on SIRT1 signaling pathways. Finally, kaempferol triggers anti-inflammatory and antioxidant effects through SIRT1 induction. This review aims to summarize recent findings on the properties of phytochemicals in the modulation of sirtuin activity, with a particular focus on biochemical aspects.

Current Treatment of Melanoma Brain Metastases.

Melanoma is a type of skin cancer in which there is a strong correlation between its occurrence and exposure to ultraviolet radiation. Although it is not the most common skin cancer, it has the highest mortality rate of all skin cancers. The prognosis of patients is significantly worsened by melanoma metastasis to the brain, which often occurs in patients with advanced disease. The formation and development of melanoma metastases to the brain involve a very complex process, and their mechanisms are not fully understood. One of the ways for metastatic melanoma cells to survive and develop cancer in the brain environment is the presence of oncogenic BRAF mutation, which occurs in up to 50% of metastatic melanoma cases. Before discovering new methods of treating metastases, the overall survival of patients with this disease was 6 months. Currently, research is being conducted on new drugs using immunotherapy (immune checkpoint inhibitors: anti-PD-1, anti-CTLA-4) and targeted therapy (BRAF and MEK inhibitors) to improve the prognosis of patients. In this article, we summarize the current state of knowledge about the results of treating brain metastases with new systemic therapies.

Cyclic AMP but Not Calmodulin as a Potential Wasoconstrictor in Simulated Reperfusion.

The phenomena of ischemia and reperfusion are associated with the pathological background of cardiovascular diseases. Ischemia is initiated by ischemia reperfusion injury (IRI), which involves disruption of intracellular signaling pathways and causes cell death. The aim of this study was to assess the reactivity of vascular smooth muscle cells in the conditions of induced ischemia and reperfusion, and to determine the mechanisms leading to contractility disorders. This study was conducted using classical pharmacometric methods on an isolated model of the rat caudal artery. The experiment consisted of the analysis of the final and initial perfusate pressure measurements after induction of arterial contraction with phenylephrine in the presence of forskolin and A7 hydrochloride, two ligands modifying the contractility of vascular smooth muscle cells (VSMC). The pharmacometric analysis showed that in simulated reperfusion, cyclic nucleotides have a vasoconstrictive effect, and calmodulin has a vasodilating effect. The responsiveness of vascular smooth muscle cells to the vasopressor effects of α1-adrenomimetics during reperfusion may change uncontrollably, and the effects of secondary messengers may be counter physiological. Further studies are needed to evaluate the function of other second messengers on VSMCs in the process of ischemia and reperfusion.

Vitamin D Supplementation and Its Impact on Different Types of Bone Fractures.

Vitamin D helps to balance the levels of calcium and phosphorus to maintain proper bone structure. It is also involved in essential biological roles and displays a wide spectrum of potential benefits in the human body. Since there are many types of fractures that occur at specific ages and due to different circumstances, the influence of vitamin D on the frequency of a particular fracture may differ. Thus, the authors investigated the possible preventive effect of vitamin D on the risks of vertebral fractures, hip fractures, stress fractures and pediatric fractures. Additional aspects of vitamin D, especially on recuperation after injures and its impact on the severity of particular fractures, were also discussed. It was suggested that vitamin D supplementation may contribute to a reduction in hip fracture risk due to reduced bone turnover, decreased frequency of falls and improved muscle function. Furthermore, vitamin D appears to lower the risk of stress fractures in athletes and military recruits. Due to a nonunified protocol design, presented investigations show inconsistencies between vitamin D supplementation and a decreased risk of vertebral fractures. However, a vitamin D preventive effect on pediatric fractures seems to be implausible.