The Precious Potential of the Sacred Tree Chamaecyparis obtusa (Siebold & Zucc.) Endl. as a Source of Secondary Metabolites with Broad Biological Applications.

Chamaecyparis obtusa (Siebold & Zucc.) Endl., which belongs to the Cupressaceae family, occurs naturally in North America and Asia, especially in Korea, Taiwan and Japan, where it is an evergreen, coniferous, sacred, ethnic tree. It has many useful varieties that are widespread throughout the world and grown for decorative purposes. It is most commonly used as an ornamental plant in homes, gardens or parks. It is also widely used in many areas of the economy; for example, its wood is used in architecture as well as furniture production. In addition, oil extracted from Chamaecyparis obtusa is increasingly used in cosmetology for skin care. Due to its wide economic demand, mainly in Japan, it represents the largest area of plantation forest. Despite this, it is on the red list of endangered species. Its use in ethnopharmacology has led to more and more research in recent years in an attempt to elucidate the potential mechanisms of its various biological activities, such as antimicrobial, antioxidant, anticancer, antidiabetic, antiasthmatic, anti-inflammatory, antiallergic, analgesic and central nervous system effects. It has also been shown that Chamaecyparis obtusa can be used as an insect repellent and an ingredient in plant disease treatment. This thesis provides a comprehensive review of the biological studies to date, looking at different areas of the economic fields of potential use of Chamaecyparis obtusa.

New insights into the regulation of TGF-ß/Smad and MPK signaling pathway gene expressions by nasal allergen and methacholine challenge test in asthma.

Background: Asthma is a heterogeneous chronic inflammatory disease of the bronchi, the course of which is significantly influenced by extrinsic factors (specific and non-specific). Methods: The aim of this study was to evaluate the effect of these factors represented by nasal allergen challenge (specific factors) and methacholine challenge test (non-specific) on changes in mRNA expression of genes encoding the TGF-ß (TGF-ß1 and TGF-ß3)‒Smad (mitogen-activated protein kinase 1/3 [MPK1/3], Smad1/3/6/7) signaling pathway in asthmatic patients. Results: Seventy-five subjects were included in the study, of whom 27 were applied an intranasal allergen provocation and 48 a methacholine provocation. There were 9 men and 18 women in the intranasal provocation group, and 17 men and 31 women in the methacholine test group. We found that both examined the types of challenges contributed to changes in the relative expression of genes of the TGF-ß (TGF-ß1 and TGF-ß3)‒Smad (MPK1/3, Smad1/3/6/7) signaling pathway in asthmatic patients. A decrease was noted for MAPK1, MAPK3, Smad3, Smad6, and Smad7 genes and an increase of up to 2.5 times for TGF-ß1 gene. Conclusions: Our experiment allows us to conclude that the change in the mRNA expression of the TGF-ß1-MPK1/3 and Smad3/6/7 genes occurs after an intranasal allergen and bronchial methacholine challenge.

Hidden in Plants-A Review of the Anticancer Potential of the Solanaceae Family in In Vitro and In Vivo Studies.

Many of the anticancer agents that are currently in use demonstrate severe side effects and encounter increasing resistance from the target cancer cells. Thus, despite significant advances in cancer therapy in recent decades, there is still a need to discover and develop new, alternative anticancer agents. The plant kingdom contains a range of phytochemicals that play important roles in the prevention and treatment of many diseases. The Solanaceae family is widely used in the treatment of various diseases, including cancer, due to its bioactive ingredient content. The purpose of this literature review is to highlight the antitumour activity of Solanaceae extracts-single isolated compounds and nanoparticles with extracts-and their synergistic effect with chemotherapeutic agents in various in vitro and in vivo cancer models. In addition, the biological properties of many plants of the Solanaceae family have not yet been investigated, which represents a challenge and an opportunity for future anticancer therapy.

Effect of haloperidol and amisulpride on the production of malondialdehyde in reaction to free radical attack on deoxyrybosis.

Knowledge of free radicals has a huge impact on the development of medicine not only because of diseases caused by reactive oxygen species, but also because of their harmful role in the pharmacotherapy of various diseases. Hence, many researchers are looking for both the mechanisms responsible for induction of oxidative stress in the body, and an effective method to scavenge free radicals. AIM: The aim of our study was to test the in vitro antioxidant properties of two known neuroleptics - haloperidonol and amisulpride, which are commonly used in the treatment of schizophrenia. MATERIALS AND METHODS: The study took advantage of the properties of hydroxyl radical degrading deoxyrybosis to malondialdehyde (MDA). Fenton reaction was used to produce the free radical. For this purpose, deoxyrybosis was incubated under appropriate conditions with FeSO4 (0.5mM), EDTA (1mM), H2O2 (14mM) and haloperidol or amisulpride at 1, 5, 20 or 50 umol/l concentrations. A clean system (containing no medicines) was a positive control. Thiobarbituric acid (TBA) was subsequently added to the reaction mixtures in the presence of trichloroacetic acid. RESULTS: The study took advantage of the properties of hydroxyl radical degrading deoxyrybosis to malondialdehyde (MDA). Fenton reaction was used to produce the free radical. For this purpose, deoxyrybosis was incubated under appropriate conditions with FeSO4 (0.5mM), EDTA (1mM), H2O2 (14mM) and haloperidol or amisulpride at 1, 5, 20 or 50 umol/l concentrations. A clean system (containing no medicines) was a positive control. Thiobarbituric acid (TBA) was subsequently added to the reaction mixtures in the presence of trichloroacetic acid. CONCLUSIONS: The results demonstrated that both haloperidol and amisulpride inhibit the degradation of deoxyrybosis to MDA, so they show antioxidant properties under the test conditions.

Psychological responses and associated factors during the initial stage of the coronavirus disease (COVID-19) epidemic among the adult population in Poland - a cross-sectional study.

INTRODUCTION: The study aimed to assess the emotional state, the occurrence of symptoms of depression, anxiety, and stress, as well as the quality of life of adults living in Poland during the first weeks of the COVID-19 pandemic. METHOD: The study was conducted on a group of 700 people aged 18 and over living in Poland. An anonymous online questionnaire was used in this cross-sectional study. The psychological impact of COVID-19 was measured using the Revised Event Impact Scale (IES-R) and the Depression, Anxiety, and Stress Scale (DASS - 21). The quality of life was assessed using the WHOQOL-BREF. RESULTS: In Poland, a high average level of post-traumatic stress was found as a result of the COVID-19 pandemic, with at least the minimum level occurring in all surveyed people. There was also a high incidence of depression (48.00%), anxiety (39.29%), and stress (54.86) in the first phase of the pandemic. The average level of quality of life in Poland was the lowest for the physical domain and amounted to 49.56 (SD = 11.71). The standard of living in the psychological domain was 60.26 (SD = 13.14). CONCLUSIONS: The pandemic is having a significant impact on human mental health. The very high average levels of post-traumatic stress, stress, anxiety, and depression as well as low quality of life make it necessary to consider interventions that will favor the use of more adaptive defense mechanisms and build mental resilience during an infectious disease pandemic and its long-term consequences.

Perspective of SGLT2 Inhibition in Treatment of Conditions Connected to Neuronal Loss: Focus on Alzheimer's Disease and Ischemia-Related Brain Injury.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are oral anti-hyperglycemic agents approved for the treatment of type 2 diabetes mellitus. Some reports suggest their presence in the central nervous system and possible neuroprotective properties. SGLT2 inhibition by empagliflozin has shown to reduce amyloid burden in cortical regions of APP/PS1xd/db mice. The same effect was noticed regarding tau pathology and brain atrophy volume. Empagliflozin presented beneficial effect on cognitive function, which may be connected to an increase in cerebral brain-derived neurotrophic factor. Canagliflozin and dapagliflozin may possess acetylcholinesterase inhibiting activity, resembling in this matter Alzheimer's disease-registered therapies. SGLT2 inhibitors may prove to impact risk factors of atherosclerosis and pathways participating both in acute and late stage of stroke. Their mechanism of action can be related to induction in hepatocyte nuclear factor-1α, vascular endothelial growth factor-A, and proinflammatory factors limitation. Empagliflozin may have a positive effect on preservation of neurovascular unit in diabetic mice, preventing its aberrant remodeling. Canagliflozin seems to present some cytostatic properties by limiting both human and mice endothelial cells proliferation. The paper presents potential mechanisms of SGLT-2 inhibitors in conditions connected with neuronal damage, with special emphasis on Alzheimer's disease and cerebral ischemia.

Adaptation and validation of the Polish version of the Beliefs about Medicines Questionnaire among cardiovascular patients and medical students.

BACKGROUND: The Beliefs about Medicines Questionnaire (BMQ) is the leading tool intended to assess the cognitive representation of medication, however, the validated Polish version of the questionnaire is lacking. AIMS: To adapt the original BMQ tool to the Polish language (BMQ-PL) and to validate it. MATERIALS AND METHODS: The BMQ was adapted to Polish according to widely accepted guidelines. A total of 311 cardiovascular in- and outpatients as well as medical students taking chronic medication were surveyed to assess data-to-model fit and internal consistency of the measure. The criterion-related validity was determined with the use of Polish version of the Adherence to Refills and Medications Scale. Confirmatory and exploratory factor analyses were used, as well as general linear modeling. RESULTS: The BMQ-PL exhibited the same factorial structure as the original questionnaire and all the items loaded on their expected factors. Internal consistency of the questionnaire was satisfactory in the group of cardiovascular patients (Cronbach's alpha ranging from 0.64 to 0.82 and McDonald's omega from 0.90 to 0.91). There were significant correlations in the predicted directions between all BMQ-PL subscales and the measure of drug adherence in cardiovascular outpatients, but not in inpatients. Medical students may conceptualize the beliefs about medicines in a different way; as a result, a modified version of the BMQ-PL-General, suitable for medically-educated people, was proposed. CONCLUSION: The BMQ-PL exhibits satisfactory proof of validity to be used among cardiovascular patients.

Plant Extracts as a Natural Source of Bioactive Compounds and Potential Remedy for the Treatment of Certain Skin Diseases.

Skin ailments present a major health burden in both developed and undeveloped countries. Maintaining healthy skin is important for a healthy body. Medicinal plants have long provided reliable therapy in the treatment of skin diseases in humans through a diverse range of bioactive molecules. Skin diseases may have a various basis, or may be genetically determined; together, they constitute approximately 34% of all occupational diseases encountered in people of all ages. Of these, melanoma is one of the most dangerous forms, with very poor prognosis for patients if it is diagnosed too late. This review of the literature over the past five years examines the role and utilities of plant extracts in treating various skin diseases such as atopic dermatitis, acne or melanoma with various potential mechanisms of action.

Vasculoprotective Effects of Vildagliptin. Focus on Atherogenesis.

Vildagliptin is a representative of Dipeptidyl Peptidase-4 (DPP-4) inhibitors, antihyperglycemic drugs, approved for use as monotherapy and combination therapy in type 2 diabetes mellitus. By inhibiting enzymatic decomposition, DPP-4 inhibitors increase the half-life of incretins such as GLP-1 (Glucagon-like peptide-1) and GIP (Gastric inhibitors polypeptide) and prolong their action. Some studies present results suggesting the anti-sclerotic and vasculoprotective effects of vildagliptin reaching beyond glycemic control. Vildagliptin is able to limit inflammation by suppression of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathway and proinflammatory agents such as TNF-α (tumor necrosis factor α), IL-1ß (Interleukin-1ß), and IL-8 (Interleukin 8). Moreover, vildagliptin regulates lipid metabolism; attenuates postprandial hypertriglyceridemia; and lowers serum triglycerides, apolipoprotein B, and blood total cholesterol levels. This DPP-4 inhibitor also reduces macrophage foam cell formation, which plays a key role in atheromatous plaque formation and stability. Vildagliptin reduces vascular stiffness via elevation of nitric oxide synthesis, improves vascular relaxation, and results in reduction in both systolic and diastolic blood pressure. Treatment with vildagliptin lowers the level of PAI-1 presenting possible antithrombotic effect. By affecting the endothelium, inflammation, and lipid metabolism, vildagliptin may affect the development of atherosclerosis at its various stages. The article presents a summary of the studies assessing vasculoprotective effects of vildagliptin with special emphasis on atherogenesis.

Resveratrol's Impact on Vascular Smooth Muscle Cells Hyporeactivity: The Role of Rho-Kinase Inhibition.

Resveratrol (3,5,4'-trihydroxystilbene) is a chemical compound belonging to the group of polyphenols and flavonoids. The aim of the present study was to determine the influence of resveratrol application along with certain modulating factors, such as 8Br-cGMP-activator of cGMP-dependent protein kinases, HA-1077-Rho-kinase inhibitor, and Bay K8644-calcium channel agonist, on VMSCs constriction triggered by phenylephrine. Resveratrol at a dose of 10 mg/kg/24 h administered for 4 weeks reduced the reactivity of the arteries to the pressure action of catecholamines. Tests performed after four weeks of resveratrol administration showed that 8Br-cGMP at the concentrations of 0.01 mM/l and 0.1 mM/l intensifies this effect. Simultaneous resveratrol and Bay K8644 administration led to a significant decrease in contractility compared to the vessels collected from animals (Res-). This effect was dependent on the concentration of Bay K8644. Resveratrol seems to be counteractive against Bay K8644 by blocking L-type calcium channels. As the concentration of HA-1077 increased, there was a marked hyporeactivity of the vessels to the pressure effects of phenylephrine. The results indicate synergy between resveratrol and Rho-kinase inhibition.

Neuroprotective Properties of Linagliptin: Focus on Biochemical Mechanisms in Cerebral Ischemia, Vascular Dysfunction and Certain Neurodegenerative Diseases.

Linagliptin is a representative of dipeptidyl peptidase 4 (DPP-4) inhibitors which are registered and used effectively in a treatment of diabetes mellitus type 2. They increase the levels of active forms of endogenous incretins such as GLP-1 and GIP by inhibiting their enzymatic decomposition. Scientific reports suggest beneficial effects of linagliptin administration via immunological and biochemical pathways involved in neuroprotective processes of CNS. Linagliptin's administration leads to a decrease in the concentration of proinflammatory factors such as: TNF-α, IL-6 and increases the number of anti-inflammatory patrolling monocytes CX3CR1bright. Significant reduction in Aß42 level has been associated with the use of linagliptin implying potential application in Alzheimer's disease. Linagliptin improved vascular functions by increasing production of nitric oxide (NO) and limiting concentration of apolipoprotein B. Linagliptin-induced decrease in macrophages infiltration may provide improvement in atheromatous plaque stabilization. Premedication with linagliptin increases neuron's survival after stroke and augments neuronal stem cells proliferation. It seems to be connected with SDF-1α/CXCR4 signaling pathway. Linagliptin prevented abnormal proliferation and migration of rat brain microvascular endothelial cells in a state of hypoperfusion via SIRT1/HIF-1α/VEGF pathway. The article presents a summary of the studies assessing neuroprotective properties of linagliptin with special emphasis on cerebral ischemia, vascular dysfunction and neurodegenerative diseases.

Liraglutide and its Neuroprotective Properties-Focus on Possible Biochemical Mechanisms in Alzheimer's Disease and Cerebral Ischemic Events.

Liraglutide is a GLP-1 analog (glucagon like peptide-1) used primarily in the treatment of diabetes mellitus type 2 (DM2) and obesity. The literature starts to suggest that liraglutide may reduce the effects of ischemic stroke by activating anti-apoptotic pathways, as well as limiting the harmful effects of free radicals. The GLP-1R expression has been reported in the cerebral cortex, especially occipital and frontal lobes, the hypothalamus, and the thalamus. Liraglutide reduced the area of ischemia caused by MCAO (middle cerebral artery occlusion), limited neurological deficits, decreased hyperglycemia caused by stress, and presented anti-apoptotic effects by increasing the expression of Bcl-2 and Bcl-xl proteins and reduction of Bax and Bad protein expression. The pharmaceutical managed to decrease concentrations of proapoptotic factors, such as NF-κB (Nuclear Factor-kappa ß), ICAM-1 (Intercellular Adhesion Molecule 1), caspase-3, and reduced the level of TUNEL-positive cells. Liraglutide was able to reduce the level of free radicals by decreasing the level of malondialdehyde (MDA), and increasing the superoxide dismutase level (SOD), glutathione (GSH), and catalase. Liraglutide may affect the neurovascular unit causing its remodeling, which seems to be crucial for recovery after stroke. Liraglutide may stabilize atherosclerotic plaque, as well as counteract its early formation and further development. Liraglutide, through its binding to GLP-1R (glucagon like peptide-1 receptor) and consequent activation of PI3K/MAPK (Phosphoinositide 3-kinase/mitogen associated protein kinase) dependent pathways, may have a positive impact on Aß (amyloid beta) trafficking and clearance by increasing the presence of Aß transporters in cerebrospinal fluid. Liraglutide seems to affect tau pathology. It is possible that liraglutide may have some stem cell stimulating properties. The effects may be connected with PKA (phosphorylase kinase A) activation. This paper presents potential mechanisms of liraglutide activity in conditions connected with neuronal damage, with special emphasis on Alzheimer's disease and cerebral ischemia.

Possible Effects of Proton Pump Inhibitors on Hearing Loss Development.

Considered safe and often available as over-the-counter (OTC) drugs, proton pump inhibitors (PPI) are one of the most frequently used medicines. Over recent years much research analyzing PPI has been conducted and these studies shed light on PPI side effects and the mechanisms of these processes. In this study we summarize the findings of these studies and through deduction present some hypotheses on the impact of PPI on health. Of particular interest is the impact of PPI on hearing loss development. However, despite this side effect being localized, its mechanisms are complex, systemic and involve changes in whole body. This paper summarizes how through, inter alia, alterations in the circulatory system, respiratory system, central nervous system and metabolism PPI can cause hearing impairment, which can occur in every age group and is connected with long-term use of this group of drugs. This article also discusses the role PPI plays in the acceleration of presbycusis development, in relation to the fact that older people are the group who most frequently use PPI in long term. Hearing loss negatively impacts affects quality of life, especially among older patients who are also the most afflicted group; administration of PPI should therefore be considered carefully, taking into consideration all potential benefits and side effects.

Beneficial Effects of Resveratrol Administration-Focus on Potential Biochemical Mechanisms in Cardiovascular Conditions.

Resveratrol (RV) is a natural non-flavonoid polyphenol and phytoalexin produced by a number of plants such as peanuts, grapes, red wine and berries. Numerous in vitro studies have shown promising results of resveratrol usage as antioxidant, antiplatelet or anti-inflammatory agent. Beneficial effects of resveratrol activity probably result from its ability to purify the body from ROS (reactive oxygen species), inhibition of COX (cyclooxygenase) and activation of many anti-inflammatory pathways. Administration of the polyphenol has a potential to slow down the development of CVD (cardiovascular disease) by influencing on certain risk factors such as development of diabetes or atherosclerosis. Resveratrol induced an increase in Sirtuin-1 level, which by disrupting the TLR4/NF-κB/STAT signal cascade (toll-like receptor 4/nuclear factor κ-light-chain enhancer of activated B cells/signal transducer and activator of transcription) reduces production of cytokines in activated microglia. Resveratrol caused an attenuation of macrophage/mast cell-derived pro-inflammatory factors such as PAF (platelet-activating factor), TNF-α (tumour necrosis factor-α and histamine. Endothelial and anti-oxidative effect of resveratrol may contribute to better outcomes in stroke management. By increasing BDNF (brain-derived neurotrophic factor) serum concentration and inducing NOS-3 (nitric oxide synthase-3) activity resveratrol may have possible therapeutical effects on cognitive impairments and dementias especially in those characterized by defective cerebrovascular blood flow.