Colorectal cancer tumour markers and biomarkers:Recenttherapeutic advances

Colorectal cancer(CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments.

Role of environmental pollution in irritable bowel syndrome

Irritable bowel syndrome(IBS),with the prevalence of 10%-20 % of the population has become an emerging problem worldwide. IBS is a functional gastrointestinal(GI) disorder characterized by abdominal pain or discomfort and altered bowel habits. The etiology of IBS contains genetic,psychological,and immunological factors,and has not been fully elucidated; of note,recent studies also point at environmental pollution and its role in the development of functional GI diseases. In this review we focus on several environmental factors,such as bacterial contamination,air pollution,radiation and even stress as potential triggers of IBS. We discuss associated disturbances in homeostasis,such as changes in intestinal microbiome and related pathophysiological mechanisms. Based on the effect of environmental factors on the GI tract,we also propose novel targets in IBS treatment.

Artificial meat? Feasible approach based on the experience from cell culture studies

This short review is to list pros and cons which are based on the literature and personal experience in cell culture studies related to possible commercial production of artificial meat as functional food. The general view of muscle composition and determinants of meat quality are shortly described. Principles of muscle cell propagation in culture and mutual relationships between different cell types present in this organ are briefly discussed. Additionally, the effects of some cytokines and growth factors for muscle cell growth and muscle tissue development are indicated. Finally, conclusion remarks related to detrimental consequences of meat production to natural environment as well as personal opinion of author on the prospects of artificial meat production are declared.

The role of degenerative pathways in the development of irreversible consequences after brain ischemia

Ischemic stroke and irreversible consequences:Ischemic stroke in humans is the second most common cause of death in the world(Mozaffarian et al.,2016).The outcomes after a stroke are often dependent on complications,including motor disorders,depression and dementia(Pluta et al.,2018a),which causes a high risk of re-hospitalization and/or palliative care.This is also the main reason for long-term disability in people after stroke,with up to half of those who survived the stroke will not regain their independence until the end of their lives(Mozaffarian et al.,2016).According to epidemiological forecasts,human ischemic stroke will soon become the dominant cause of death worldwide(Bejot et al.,2016)as well as dementia with the phenotype of Alzheimer’s disease(AD;Kim and Lee 2018).It is suggested that human ischemic stroke and experimental brain ischemia in animals are associated with the possible development of AD neuropathology(Pluta et al.,2018a).

Dysfunctional glia:contributors to neurodegenerative disorders

Astrocytes are integral components of the central nervous system,where they are involved in numerous functions critical for neuronal development and functioning,including maintenance of blood-brain barrier,formation of synapses,supporting neurons with nutrients and trophic factors,and protecting them from injury.These roles are markedly affected in the course of chronic neurodegenerative disorders,often before the onset of the disease.In this review,we summarize the recent findings supporting the hypothesis that astrocytes play a fundamental role in the processes contributing to neurodegeneration.We focus onα-synucleinopathies and tauopathies as the most common neurodegenerative diseases.The mechanisms implicated in the development and progression of these disorders appear not to be exclusively neuronal,but are often related to the astrocytic-neuronal integrity and the response of astrocytes to the altered microglial function.A profound understanding of the multifaceted functions of astrocytes and identification of their communication pathways with neurons and microglia in health and in the disease is of critical significance for the development of novel mechanism-based therapies against neurodegenerative disorders.

Misdiagnosed Aortic Intramural Hematoma and the Role of Intravascular Ultrasound Imaging in Detection of Acute Aortic Syndrome:A Case Report

Acute aortic syndrome includes classic aortic dissection,aortic intramural hematoma,and penetrating atherosclerotic ulcer– a group of conditions that are defined by their dynamic evolution and similar clinical manifestation.Accurate diagnosis and prompt treatment are essential as all the aforementioned conditions are a signifi cant threat to a patient’s life.However,acute aortic syndrome and especially aortic intramural hematoma may be challenging diagnostic problems.Intravascular ultrasound imaging is a diagnostic method that can be useful for more thorough evaluation of the aortic lesion and can particularly aid in discerning the different forms of acute aortic syndrome.We present a case of a patient with aortic intramural hematoma that was missed by conventional imaging studies but was successfully visualized with intravascular ultrasound imaging.

To treat or not to treat Alzheimer’s disease by the ketogenic diet? That is the question

Alzheimer’s disease (AD) and current treatments: AD is a serious neurological disorder worldwide that affects about 26 million people,and whose prevalence has been calculated to quadruple by 2050,thus reaching over 1% of the total population,with the highest prevalence occurring in both adults and elderly (Pluta et al.,2018).Neurodegenerative processes of the sporadic form of AD probably start 20 years before the clinical onset of the disorder (Pluta et al.,2018).This disease is the most important cause of dementia in world aged society (~75%).AD is a disorder that affects not only patients but also their caregivers.The social and economic burden associated with AD was calculated as an example in the United States alone;600 billion dollars annually is spent on caring for AD patients (Pluta et al.,2018).AD is the one of the great health-care challenges of the 21st century.The incidence of AD,a chronic and progressive neurodegenerative disorder,is increasing,as well as the need for efficient methods of diagnosis,prevention and treatment (Pluta et al.,2018).The characteristic clinical and neuropathological hallmarks of AD are: dementia as the main clinical symptom and in post-mortem neuropathological examination,the presence of amyloid plaques as well as neurofibrillary tangles and loss of neurons in the brain of AD patients.The role of amyloid and tau protein is questioned in the etiology of AD and other causes such as ischemic etiology are being considered (Pluta and U?amek-Kozio?,2019).There are several treatments that are not causal but symptomatic that are not effective,especially for advanced disease.To date,only a few drugs are approved,such as acetylcholinesterase inhibitors and memantine.Drugs that regulate partly the activity of neurotransmitters and partly alleviate behavioral symptoms.Other treatment options include active and passive immunization,anti-aggregation specifics,and secretase inhibitors.The road to clarity AD etiology,early final ante mortem diagnosis and treatment has been one fraught with a wide range of complications and numerous revisions with a lack of a final solution.Research has recently been launched to identify new mechanisms underlying AD that could be the target of new prevention strategies (Pluta and U?amek-Kozio?,2019).Therefore,other treatment options can be recommended,and the ketogenic diet seems to be an interesting last resort solution at the moment (Rusek et al.,2019).The diet contains large amounts of fat and low carbohydrates with vitamin supplementation.New scientific articles suggest that a low-carbohydrate and high-fat ketogenic diet may help alleviate the brain damage in AD (Ota et al.,2019;Rusek et al.,2019).A ketogenic diet can alleviate the effects of impaired glucose metabolism in AD by providing ketones as an additional source of energy.Here,based on new data,we have presented that a ketogenic diet can be effective in preventing and treating AD,but both ketone bodies production and carbohydrate reduction are needed to achieve this.

Genes associated with Alzheimer's disease affecting ischemic neurodegeneration of the hippocampal CA3 region

Neurodegeneration in the brain after ischemia with reperfusion mimicking the neuropathology of Alzheimer's disease:Brain ischemia with reperfusion,which is one of the main causes of morbidity and mortality in the world,triggers various neuropathological changes characteristic for Alzheimer's disease(AD)such as increased blood-brain barrier permeability,excitotoxicity,necrosis,autophagy,mitophagy,apoptosis,neuroinflammation,amyloid plaques,neurofibrillary tangles,cerebral vessel pathology,and brain atrophy that lead to the death of neurons,deteriorating motor,sensory and cognitive functions(Figure 1)(Kato et al.,1988;Wisniewski et al.,1995;Van Groen et al.,2005;Kocki et al.,2015;Ułamek-Koziołet al.,2016,2017,2019).Brain ischemia is recognized as a major contributor to the dysfunction of an aging brain and the development of neurodegenerative diseases,including AD(Pluta,2019).

The role of diet in the management of MAFLD-why does a new disease require a novel,individualized approach?

In 2020,international consensus guidelines recommended renaming a non-alcoholic fatty liver disease(NAFLD)to metabolic-associated fatty liver disease(MAFLD)(1).However,these two terms are not interchangeable.Diagnosis of MAFLD is established while hepatic steatosis(diagnosed by the use of non-invasive methods as well as liver biopsy)is accompanied by overweight/obesity or type 2 diabetes(T2D)or two or more metabolic risk factors,including increased waist circumference(with cut off values specific for the population),arterial hypertension,hypertriglyceridemia,low high-density lipoprotein cholesterol(HDL-C)(<40 mmol/L in women and<50 mmol/L in men),prediabetes(impaired fasting glucose,impaired glucose tolerance or glycated hemoglobin 5.7-6.4%).

Novel opioid-neurotensin-based hybrid peptide with spinal long-lasting antinociceptive activity and a propensity to delay tolerance development

The behavioral responses exerted by spinal administration of the opioid-neurotensin hybrid peptide, PK23, were studied in adult male rats. The antinociceptive effect upon exposure to a thermal stimulus, as well as tolerance development, was assessed in an acute pain model. The PK23 chimera at a dose of 10 nmol/rat produced a potent pain-relieving effect, especially after its intrathecal administration. Compared with intrathecal morphine, this novel compound was found to possess a favourable side effect profile characterized by a reduced scratch reflex, delayed development of analgesic tolerance or an absence of motor impairments when given in the same manner, though some animals died following barrel rotation as a result of its i.c.v. administration(in particular at doses higher than 10 nmol/rat). Nonetheless, these results suggest the potential use of hybrid compounds encompassing both opioid and neurotensin structural fragments in pain management. This highlights the enormous potential of synthetic neurotensin analogues as promising future analgesics.