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Topic Review
Mitochondria in the Central Nervous System
Nearly half a century has passed since the discovery of cytoplasmic inheritance of human chloramphenicol resistance. The inheritance was then revealed to take place maternally by mitochondrial DNA (mtDNA) and mutations in mtDNA were identified as a cause of severe inheritable metabolic diseases with neurological manifestation. A growing number of preclinical studies have revealed that animal behaviors are influenced by the impairment of mitochondrial functions. Indeed, as high as 54% of patients with one of the most common primary mitochondrial diseases, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, present psychiatric symptoms. Mitochondrial functions are observed to be compromised and to become less resilient under continuous stress. Furthermore, stress, inflammation, mitochondrial impairment have been linked to the activation of the tryptophan–kynurenine metabolic system, which observably contributes to the development of pathological conditions including neurological and psychiatric disorders.
  • 844
  • 29 Aug 2022
Topic Review
Resting Metabolic Rate
Resting metabolic rate (RMR) reflects the energy expended by the human body in a prolonged resting state in the absence of food digestion, physical or cognitive activities. RMR declines with age and has been related to changes in body composition and health status. In this study we aimed to assess whether having specific age-associated diseases, or the development thereof, correlate with RMR changes over time. Information on such associations is important to understand the energetic burden of specific diseases and whether early perturbation in energetic metabolism can inform impending health deterioration and future pathology.
  • 839
  • 04 Nov 2020
Topic Review
Fabry Nephropathy
Fabry disease (FD; OMIM#301500) is an X-linked lysosomal storage disorder associated with inherited or de novo disease causing variants in the α-galactosidase A gene (GLA; OMIM*300644). Reduced or even absent α-galactosidase A (α-Gal A; EC 3.2.1.22) activity leads to accumulation of glycosphingolipids with terminal α-D-galactosyl residues, especially globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) in plasma, urine and different organ systems, mainly cardiac, renal, endothelial and neuronal. The major physiological source of Gb3 is globoside, a glycolipid of erythrocytes and cells membranes found in different tissues. Kidneys are very frequently affected in patients with Fabry disease regardless of gender. Most important manifestations of Fabry nephropathy are proteinuria and slowly progressive chronic kidney disease, which can in some cases lead to end stage renal disease.
  • 839
  • 27 Sep 2020
Topic Review
The Mechanisms of Action of Pulsed Radiofrequency
Radiofrequency energy is a common treatment modality for chronic pain. While there are different forms of radiofrequency-based therapeutics, the common concept is the generation of an electromagnetic field in the applied area, that can result in neuromodulation (pulsed radiofrequency—PRF) or ablation. Radiofrequency (RF) energy-based procedures, whether conventional, ablative or pulsed, represent a technique commonly performed for chronic pain in a variety of musculoskeletal conditions. 
  • 839
  • 19 Oct 2022
Topic Review
Trace Elements on Glaucomatous Diseases
Glaucoma is a heterogeneous group of chronic neurodegenerative disorders characterized by a relatively selective, progressive damage to the retinal ganglion cells (RGCs) and their axons, which leads to axon loss and visual field alterations. To date, many studies have shown the role of various elements, mainly metals, in maintaining the balance of prooxidative and antioxidative processes, regulation of fluid and ion flow through cell membranes of the ocular tissues. Based on the earlier and current research results, their relationship with the development and progression of glaucoma seems obvious and is increasingly appreciated.
  • 839
  • 27 Apr 2021
Topic Review
Artemisia absinthium L.
Artemisia absinthium – wormwood (Asteraceae) – is a very important species in the history of medicine, formerly described in medieval Europe as “the most important master against all exhaustions”. It is a species known as a medicinal plant in Europe and also in West Asia and North America. The raw material obtained from this species is Artemisiae herba and Artemisiae absinthium aetheroleum. The main substances responsible for the biological activity of the herb are: the essential oil, bitter sesquiterpenoid lactones, flavonoids, another bitterness-imparting compounds, azulenes, phenolic acids, tannins and lignans. In the official European medicine, the species is used in both allopathy and homeopathy. In the traditional Asian and European medicine, it has been used as an effective agent in gastrointestinal ailments and also in the treatment of helminthiasis, anaemia, insomnia, bladder diseases, difficult-to-heal wounds, and fever. Today, numerous other directions of biological activity of the components of this species have been demonstrated and confirmed by scientific research, antiprotozoal, antibacterial, antifungal, anti-ulcer, hepatoprotective, anti-inflammatory, immunostimulatory, cytotoxic, analgesic, neuroprotective, antidepressant, procognitive, neurotrophic, and cell membrane stabilizing activities. A. absinthium is also making a successful career as a cosmetic plant. In addition, the importance of this species as a spice plant and valuable additive in the alcohol industry (famous absinthe and vermouth-type wines) has not decreased. The species has also become an object of biotechnological research.
  • 839
  • 27 Jan 2022
Topic Review
Cyclin-Dependent Kinase Inhibitors in Hematology
Genetically altered stem or progenitor cells feature gross chromosomal abnormalities, inducing modified ability of self-renewal and abnormal hematopoiesis. Cyclin-dependent kinases (CDK) regulate cell cycle progression, transcription, DNA repair and are aberrantly expressed in hematopoietic malignancies. Incorporation of CDK inhibitors (CDKIs) into the existing therapeutic regimens therefore constitutes a promising strategy. However, the complex molecular heterogeneity and different clinical presentation is challenging for selecting the right target and defining the ideal combination to mediate long-term disease control. Preclinical and early clinical data suggest that specific CDKIs have activity in selected patients, dependent on the existing rearrangements and mutations, potentially acting as biomarkers. Indeed, CDK6, expressed in hematopoietic cells, is a direct target of MLL fusion proteins often observed in acute leukemia and thus contributes to leukemogenesis. The high frequency of aberrancies in the retinoblastoma pathway additionally warrants application of CDKIs in hematopoietic neoplasms. In this review, we describe the preclinical and clinical advances recently made in the use of CDKIs. These include the FDA-approved CDK4/6 inhibitors, traditional and novel pan-CDKIs, as well as dual kinase inhibitors. We additionally provide an overview on molecular mechanisms of response vs. resistance and discuss open questions.
  • 839
  • 11 Oct 2021
Topic Review
Brain Trauma, Glucocorticoids and Neuroinflammation
Brain injury is a common cause of death and disability for people of all ages worldwide. Depending on the biomechanics, brain lesions may occur both in areas of the brain directly adjacent to the place of force application and in remote areas. The mechanisms of hippocampal damage are of particular importance, since they underlie late complications of traumatic brain injury (TBI), such as epilepsy, depression and cognitive impairment. The mechanisms of reorganization of neuronal networks in the hippocampus include long-lasting chronic neuroinflammation and secondary damage to the nervous tissue. Responses and disturbances of the hypothalamic–pituitary–adrenal (HPA) axis may play a critical role in late post-traumatic pathology, in particular by modulation of synaptic activity and neuroinflammation in the hippocampus.
  • 846
  • 25 May 2022
Topic Review
Brain Metastasis from CUP
Brain metastases (BMs) are the most common intracranial tumours in adults and occur up to 3–10 times more frequently than primary brain tumours. BMs may be the cause of the neurological presenting symptoms in patients with otherwise previously undiagnosed cancer. In up to 15% of patients with BMs, the primary tumour cannot be identified. These cases are known as BM of cancer of unknown primary (CUP) (BM-CUP). CUP has an early and aggressive metastatic spread, poor response to chemotherapy, and poor prognosis. The pathogenesis of CUP seems to be characterized by a specific underlying pro-metastatic signature.  This entry is a review of modern diagnostic and therapeutic approaches to brain metastases from unknown primary tumor.
  • 838
  • 22 Dec 2020
Topic Review
immunotherapeutic approaches of Prostate Cancer
The clinical spectrum of prostate cancer (PCa) varies from castration-naive to metastatic castration-resistant disease. Despite the administration of androgen synthesis inhibitors and chemotherapy regimens for castration-resistant prostate cancer, the treatment options for this entity are limited. The utilization of the immune system against cancer cells shows potential as a therapeutic modality for various solid tumors and hematologic malignancies. With technological advances over the last decade, immunotherapy has become an integral treatment modality for advanced solid tumors. The feasibility of immunotherapy has shown promise for patients with PCa, and with advances in molecular diagnostic platforms and our understanding of immune mechanisms, immunotherapy is reemerging as a potential treatment modality for PCa. Various combinations of individualized immunotherapy and immune checkpoint blockers with androgen receptor-targeted therapies and conventional cytotoxic agents show promise. This article will review the current status of immunotherapy, including new discoveries and precision approaches for PCa, and discuss future directions in the continuously evolving landscape of immunotherapy.
  • 838
  • 28 Oct 2020
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