Use Of Pharmacological Agents Research Articles

Myeloid-derived Suppressor Cells and Multiple Sclerosis.

Myeloid-Derived Suppressor Cells (MDSCs) are a heterogeneous population of immature myeloid cells that play important roles in maintaining immune homeostasis and regulating immune responses. MDSCs can be divided into two main subsets based on their surface markers and functional properties: granulocytic MDSCs (G-MDSCs) and monocytic MDSCs (M-MDSCs). Recently greatest attention has been paid to innate immunity in Multiple Sclerosis (MS), so the aim of our review is to provide an overview of the main characteristics of MDSCs in MS and its preclinical model by discussing the most recent data available. The immunosuppressive functions of MDSCs can be dysregulated in MS, leading to an exacerbation of the autoimmune response and disease progression. Antigen-specific peptide immunotherapy, which aims to restore tolerance while avoiding the use of non-specific immunosuppressive drugs, is a promising approach for autoimmune diseases, but the cellular mechanisms behind successful therapy remain poorly understood. Therefore, targeting MDSCs could be a promising therapeutic approach for MS. Various strategies for modulating MDSCs have been investigated, including the use of pharmacological agents, biological agents, and adoptive transfer of exogenous MDSCs. However, it remained unclear whether MDSCs display any therapeutic potential in MS and how this therapy could modulate different aspects of the disease. Collectively, all the described studies revealed a pivotal role for MDSCs in the regulation of MS.</p>.

Phospholipid Signaling in Crop Plants: A Field to Explore.

In plant models such as Arabidopsis thaliana, phosphatidic acid (PA), a key molecule of lipid signaling, was shown not only to be involved in stress responses, but also in plant development and nutrition. In this article, we highlight lipid signaling existing in crop species. Based on open access databases, we update the list of sequences encoding phospholipases D, phosphoinositide-dependent phospholipases C, and diacylglycerol-kinases, enzymes that lead to the production of PA. We show that structural features of these enzymes from model plants are conserved in equivalent proteins from selected crop species. We then present an in-depth discussion of the structural characteristics of these proteins before focusing on PA binding proteins. For the purpose of this article, we consider RESPIRATORY BURST OXIDASE HOMOLOGUEs (RBOHs), the most documented PA target proteins. Finally, we present pioneering experiments that show, by different approaches such as monitoring of gene expression, use of pharmacological agents, ectopic over-expression of genes, and the creation of silenced mutants, that lipid signaling plays major roles in crop species. Finally, we present major open questions that require attention since we have only a perception of the peak of the iceberg when it comes to the exciting field of phospholipid signaling in plants.

Effectiveness of cannabis use and cannabis use disorder interventions: a European and international data synthesis.

This data synthesis examined the effectiveness of behavioural and pharmacological approaches for cannabis treatment. We integrated findings from high level evidence studies and prioritised data from Europe when available. The synthesis found that only a relatively small number of published behavioural and pharmacological studies on cannabis interventions have been conducted in Europe. Applying both European and non-European data, it was found that Cognitive Behavioural Therapy (CBT) and/or Motivational Enhancement Therapy (MET) improved short-term outcomes in the frequency of cannabis use and dependency severity, although abstinence outcomes were less consistent. These improvements were typically not maintained nine months after treatment. CBT and MET (or combined CBT + MET) treatments that extend beyond four sessions were more effective than fewer sessions over a shorter duration. Combining CBT or MET (or combined CBT + MET) with adjunctive Contingency Management (CM) improved therapeutic outcomes. No pharmacotherapies have been approved for the management of cannabis use, cannabis use disorders or cannabis withdrawal. Despite only weak evidence to support the use of pharmacological agents, some are used 'off-label' to manage withdrawal symptoms outside clinical trials.

Targeting epigenetic mechanisms in amyloid-β-mediated Alzheimer's pathophysiology: unveiling therapeutic potential.

Alzheimer's disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia. Growing evidence suggests that Alzheimer's disease is associated with accumulating various amyloid-β oligomers in the brain, influenced by complex genetic and environmental factors. The memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer's disease are believed to primarily result from synaptic dysfunction. Throughout life, environmental factors can lead to enduring changes in gene expression and the emergence of brain disorders. These changes, known as epigenetic modifications, also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal activity. In this context, we highlight recent advances in understanding the roles played by key components of the epigenetic machinery, specifically DNA methylation, histone modification, and microRNAs, in the development of Alzheimer's disease, synaptic function, and activity-dependent synaptic plasticity. Moreover, we explore various strategies, including enriched environments, exposure to non-invasive brain stimulation, and the use of pharmacological agents, aimed at improving synaptic function and enhancing long-term potentiation, a process integral to epigenetic mechanisms. Lastly, we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer's disease. We suggest that addressing Alzheimer's disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.

Phitosomin drug and its use in poultry farming

Solving the problem of normalizing metabolic processes and the morphological and functional state of the liver in poultry through the use of pharmacological agents seems to be an important reserve for increasing the effi ciency of industrial poultry farming and food production. Promising in this regard are studies on the development of medicines based on plant resources, which are characterized by structural diversity, multifunctionality of pharmacological action and low toxicity. The purpose of the research was to develop the liposomal drug Phitosomin, study its pharmacological and toxicological properties and substantiate the eff ectiveness of its use in poultry farming. Biopharmaceutical research has been carried out to develop a liposomal drug for veterinary use with a multifunctional pharmacological eff ect. The component composition of the drug Phitosomin represented by lecithin, dihydroquercetin, extracts of milk thistle, common agrimony and hare’s-ear, has been substantiated. A liposomal dosage form of the drug has been developed. Its physicochemical properties and shelf life have been established. The toxicological characteristics of the drug Phitosomin were studied, which made it possible to determine the degree of safety of its use in rearing of broiler chickens. Data were obtained experimentally on the pharmacological eff ects of Phitosomin on laboratory animals and broiler chickens when modeling various pathologies. The pharmacodynamic eff ect of the drug on blood parameters and productive traits of broiler chickens has been established, and the eff ective dose of its use in rearing broiler chickens has been determined. It was established as a result of the production inspection that when Phitosomin was introduced into the main diet of poultry of the experimental group at a dose of 5 g/kg of feed during the growth and finishing periods of feeding, there was an increase in the live weight of broiler chickens by 12,6 % and the livability of livestock by 1,6 abs.% compare with the control group.

Targeting SWI/SNF Complexes in Cancer: Pharmacological Approaches and Implications.

SWI/SNF enzymes are heterogeneous multi-subunit complexes that utilize the energy from ATP hydrolysis to remodel chromatin structure, facilitating transcription, DNA replication, and repair. In mammalian cells, distinct sub-complexes, including cBAF, ncBAF, and PBAF exhibit varying subunit compositions and have different genomic functions. Alterations in the SWI/SNF complex and sub-complex functions are a prominent feature in cancer, making them attractive targets for therapeutic intervention. Current strategies in cancer therapeutics involve the use of pharmacological agents designed to bind and disrupt the activity of SWI/SNF complexes or specific sub-complexes. Inhibitors targeting the catalytic subunits, SMARCA4/2, and small molecules binding SWI/SNF bromodomains are the primary approaches for suppressing SWI/SNF function. Proteolysis-targeting chimeras (PROTACs) were generated by the covalent linkage of the bromodomain or ATPase-binding ligand to an E3 ligase-binding moiety. This engineered connection promotes the degradation of specific SWI/SNF subunits, enhancing and extending the impact of this pharmacological intervention in some cases. Extensive preclinical studies have underscored the therapeutic potential of these drugs across diverse cancer types. Encouragingly, some of these agents have progressed from preclinical research to clinical trials, indicating a promising stride toward the development of effective cancer therapeutics targeting SWI/SNF complex and sub-complex functions.

Influence of new dimethylaminoethanol derivatives, butanoic and trans-butenedioic acids, on the tolerability of hypoxia, hyperthermia, and hypothermia

BACKGROUND: The need to increase the tolerance of various extreme effects is associated not only with the expansion of human professional activity regions but also with the need to assist victims of natural and man-made disasters. The use of pharmacological agents for individual adverse effects is a well-known method; however, considering the combined effects of several physical or chemical factors, only a few references are found in the literature.&#x0D; AIM: This preclinical study aimed to examine the effectiveness of a new derivative of aminoethanol and intermediates of the Krebs cycle in relation to the isolated and combined effects of hypoxia and temperature (hyperthermia and hypothermia).&#x0D; MATERIALS AND METHODS: The fumaric salt of the amber ether of diethylaminoethanol was synthesized at St. Petersburg State University of Chemistry and Pharmacy, Department of Organic Chemistry (Head Professor I.P. Yakovlev). The study was conducted on small laboratory animals. Resistance to hypoxia was assessed by the dynamics of the altitude threshold of animals, tolerance to hyperthermia by survival in a thermal chamber at 40°C, and tolerance to hypothermia by the time of maximum swimming in water at 10–12°C. Under combined exposure, the condition of the animals was assessed by the dynamics of physical performance, hypoxia was induced by preliminary administration of the methemoglobin former sodium nitrite at a dose of 50 mg/kg, and thermal exposure was induced by placing the animal in water at 40°C (hyperthermia) or 9–11°C (hypothermia).&#x0D; RESULTS: After a single intragastric administration in a wide range of doses, the test compound stimulated the physical performance of animals and exhibited a protective effect under the isolated effects of hypobaric hypoxia, hyperthermia, and hypothermia. With combined exposure to hemic hypoxia and hyperthermia, the compound was effective at a dose of 250 mg/kg. With combined exposure to hemic hypoxia and hypothermia, efficiency was also noted at lower doses (25 and 50 mg/kg).&#x0D; CONCLUSION: Fumaric salt of dimethylaminoethanol amber ether, a new derivative of dimethylaminoethanol, butenedioic, and trans-butenedioic acids, is promising for further study as a means of increasing the body’s resistance to extreme influences.

News in pharmacology for the main medical pathologies of gestation.

Obstetric diseases represent a highly complex medical challenge, especially regarding its clinical approach. The use of pharmacological agents during pregnancy is one of the main therapeutic alternatives in this group of patients; however, there is a general lack of knowledge about its use, efficacy, and possible adverse effects that may occur in routine clinical practice, even among medical professionals themselves. The high percentage of pregnant women who undergo drugs at some point during pregnancy, together with the developments that have occurred in recent years in the field of pharmacology, show the need for a detailed analysis that shows the existing current knowledge and helps in the clinical decision making. In this sense, the aim of this work is to conduct a review of the available scientific literature on the novelties in pharmacology for the main medical pathologies of pregnancy. Thus, the role of this field in analgesia, antibiotic therapy, digestive, respiratory, urological, psychiatric and neurological pathologies will be detailed, evaluating the indications, precautions and considerations that must be taken into account for its use.

Therapeutic perspectives of high pulse repetition rate electroporation

Electroporation, a technique that uses electrical pulses to temporarily or permanently destabilize cell membranes, is increasingly used in cancer treatment, gene therapy, and cardiac tissue ablation. Although the technique is efficient, patients report discomfort and pain. Current strategies that aim to minimize pain and muscle contraction rely on the use of pharmacological agents. Nevertheless, technical improvements might be a valuable tool to minimize adverse events, which occur during the application of standard electroporation protocols. One recent technological strategy involves the use of high pulse repetition rate. The emerging technique, also referred as “high frequency” electroporation, employs short (micro to nanosecond) mono or bipolar pulses at repetition rate ranging from a few kHz to a few MHz. This review provides an overview of the historical background of electric field use and its development in therapies over time. With the aim to understand the rationale for novel electroporation protocols development, we briefly describe the physiological background of neuromuscular stimulation and pain caused by exposure to pulsed electric fields. Then, we summarize the current knowledge on electroporation protocols based on high pulse repetition rates. The advantages and limitations of these protocols are described from the perspective of their therapeutic application.

A Review on Antidiabetic Activity of Indian Medicinal Plant

Diabetes mellitus is one of the common metabolic disorders acquiring around 9.3% of adults worldwide in 2019.Since long back herbal medicines have been the highly esteemed source of medicine therefore, they have become a growing part of modern, high-tech medicine. In view of the above aspects the present review provides profiles of plants (65 species) with hypoglycemic properties, available through literature source from various database with proper categorization according to the parts used, mode of reduction in blood glucose (insulin mimetic or insulin secretagogues activity) and activephytoconstituents having insulin mimetics activity. The treatment of diabetes is mainly based on the long-term use of pharmacological agents, often expensive and causing unpleasant side effects. There is an alarming increase in the number of pharmaceuticals taken in Europe. The aim of this paper is to concisely collect information concerning the few antidiabetic or hypoglycemic raw plant materials that are present in the consciousness of Indian and relatively easily accessible to them on the market and sometimes even grown on Indian plantations.The following raw materials are discussed in this mini-reviewBoerhaavia diffusa Linn. (Nyctaginaceae),Annona squamosa Linn. (Annonaceae),Bougainvillea spectabilis Linn. (Nyctaginaceae),Cassia kleinii Wight &amp; Arn. (Caesalpiniaceae),Coscinium fenestratum Colebr. (Menispermaceae),Ficus hispida Linn. (Moraceae),Murraya koenigii Linn. (Rutaceae),White Mulberry (Morus alba L.), Acacia arabica: (Babhul), Aegle marmelos: (Bengal Quince, Bel or Bilva), Allium cepa: (onion), Allium sativum: (garlic), Aloe vera and Aloe barbadensis, Azadirachta indica: (Neem), Eugenia jambolana: (Indian gooseberry, jamun), Mangifera indica: (Mango), Momordica charantia: (bitter gourd), Ocimum sanctum: (holy basil).

MORPHOFUNCTIONAL CHANGES OF CEREBRAL CORTEX CELLS UNDER PARTIAL TRACHEAL STENOSIS IN EXPERIMENTAL ANIMALS

Introduction. To date, there are limited opportunities to study the effects of congenital airway pathology in the experiment. To study the damage to body tissues in case of impaired airway ventilation, the author's version of artificial narrowing of the tracheal lumen by applying ligatures was used. The study of morphofunctional reactions and structural changes in organs and tissues of the body made it possible to identify and study pathogenetic and target tissue targets in order to develop tactics for the treatment of this pathology in newborns. Objective: to investigate the peculiarities of ultrastructural changes in the cells of the sensorimotor cortex of the cerebral hemispheres of experimental immature animals after modelling partial tracheal stenosis. Materials and methods. Ligature was applied to young rats at the level of the upper third of the trachea, which limited the tracheal lumen by about 25-30%. After modelling the pathology of the upper respiratory tract, the appearance of characteristic wheezing sounds was noted, this allowed us to consider the experimental intervention as an analogue of the stridor model in newborns. On day 7 and day 21 of the experiment, after surgery and removal of the previously applied ligature, the ultrastructure of the sensorimotor cortex of young animals was studied and, on this basis, variants of pharmacological protective and therapeutic effects and acceleration of cerebral rehabilitation in experimental animals were proposed. Results. The development of neurodystrophic processes and damage to cell ultrastructures and blood-brain barrier functions were established. After removal of the ligature from the trachea and elimination of the artificial compression effect of this factor on the airways of animals, the observed dynamics of pathological ultrastructural changes remained virtually unchanged, even after repeated surgical procedures. This indicates the need for the use of pharmacological agents and medical technologies to restore cytomembranes in cells of the central nervous system of different types under the influence of chronic hypoxia. Conclusions. Partial tracheal stenosis causes damage to the nerve cells of the cerebrocortex, and the removal of the ligature on day 7 of the stenosis modelling experiment did not affect any ultrastructural changes compared to the results obtained in the group of animals with chronic tracheal stenosis. The restoration of lung ventilation and the nature of the data revealed indicate the absence of significant recovery changes in the nerve and vascular cells of the brain. They indicate the need for urgent therapeutic and rehabilitation measures to accelerate the restoration of the structure and functions of cerebrocortical cells in the posthypoxic period.

Vascular regenerative cells in cardiometabolic disease.

This review will provide an overview of the recent literature linking the pathophysiology of cardiometabolic disease with the depletion and dysfunction of circulating vascular regenerative (VR) cell content. Moreover, we provide rationale for the use of VR cells as a biomarker for cardiovascular risk and the use of pharmacological agents to improve VR cell content. Recent studies demonstrate the potential of VR cells as a biomarker of cardiovascular risk and as a therapeutic target. Notably, lipid-lowering agents, antihyperglycemic therapies such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, as well as exercise and weight loss, have all been found to improve VR cell content, providing mechanistic evidence supporting a role in mitigating adverse cardiovascular outcomes in people with cardiometabolic-based disease. The importance of VR cells as a biomarker in assessing cardiovascular risk is becoming increasingly apparent. This review highlights recent literature supporting the accurate use of VR cell characterization to monitor the capacity for vessel repair and novel strategies to improve vessel health. Future research is required to validate and optimize these emerging approaches.

Разработка и внедрение инновационных технологий в животноводстве для обеспечения населения высококачественными продуктами питания

Purpose. Analysis of advanced technologies for the production of livestock products and factors affecting the links of the entire production chain: "plant growing – animal husbandry – feeding and keeping technology – breeding – production technology – obtaining and processing raw materials – finished products – consumer". Discussion. The subject of discussion are issues including: consideration of systemic biotechnologies for the production of livestock raw materials; study and implementation of ways to improve its technological properties when using selection methods of reproduction and improvement of genetic parameters; the use of biologically active substances and non-traditional feed ingredients that have a positive effect when exposed to numerous stress factors; the use of pharmacological agents and biotechnological processing methods on the state of animal productivity and the functional and technological properties of meat and dairy and raw materials. Conclusion. As a result of calculations, experiments and laboratory studies, fundamentally new competitive technologies for the production of domestic livestock products have been developed and widely introduced into production, factors that contribute to the growth and improvement of the quality of the raw materials obtained for the creation of new generation food products have been studied and improved.

A Comprehensive Review of Myocardial Bridging: Exploring Diagnostic and Treatment Modalities.

Myocardial bridging (MB) is a congenital coronary artery anomaly involving an overlying myocardium's partial or complete encasement of a coronary artery segment. The obstruction can lead to significant cardiac symptoms, resulting in myocardial ischemia, arrhythmia, and sudden cardiac death. Several approaches, including invasive and non-invasive methods, have been proposed to diagnose and manage MB. Invasive modalities, such as intravascular ultrasound (IVUS) and coronary angiography, offer high specificity and sensitivity. In contrast, non-invasive methods like Doppler ultrasound, multislice computed tomography (MSCT), and magnetic resonance imaging (MRI) are advantageous due to their non-invasive nature, high sensitivity and specificity, and cost-effectiveness. Treatment options for MB mainly focus on relieving symptoms and preventing adverse outcomes. The use of pharmacological agents and surgical and percutaneous interventions has been documented in numerous studies. Studiesconclude that MB is a treatable cardiac anomaly, and acombined approach of diagnosis, treatment, and follow-up is necessary to reduce the morbidity and mortality associated with this condition.

Use of drugs in pregnant dogs and puppies - what should be considered from a pharmacological point of view?

The administration of drugs to pregnant bitches may not only pose a potential danger to the bitch but also to the fetuses. In this context, the extent of the risk also depends on the stage of gestation. Although a number of agents are known to have a fetotoxic and/or teratogenic potential, insufficient knowledge concerning their potential risk to the embryo/fetus is available for the majority of drugs.Arranged in groups of active substances, a selection of drugs that are assumed to be safe according to the current state of knowledge is provided. Drugs for which there is insufficient knowledge or which are clearly contraindicated are also mentioned.The second part of this overview covers the use of medicines in puppies. The physiology of a puppy does not simply correspond to that of a small dog. Only very few drugs posess valid pharmacological data for use in puppies. However, a subset of restrictions on the use of pharmacologic agents may be derived from the specifics of puppy physiology.The recommendations made do not claim to be complete and no guarantee for accuracy is provided, as these have been compiled from a literature review. In certain cases, the recommendations are even contradictory.Veterinarians are therefore encouraged to report all adverse events associated with treatments of pregnant bitches and puppies within the framework of pharmacovigilance. This is the only way to close gaps in knowledge about the treatment of these special patients.

Nonalbuminuric diabetic kidney disease: what is known? Literature review

Urinal albumin excretion is widely used in clinical practice as an indicator of diabetic renal injury. In accordance with a classical conception of diabetic nephropathy clinical course, an albuminuria usually precedes a reduction of renal function.&#x0D; The review is devoted to discussion of an actual problem of contemporary nephrology, nonalbuminuric diabetic kidney disease (NADKD), its prevalence increasingly grows in population of patients with type 2 diabetes mellitus due to efficacy of glucose lowering, hypotensive, hypolipidemic therapy and smoking cessation. NADKD is more frequently revealed among females; it is associated with arterial hypertension and ischemic heart disease. Renal changes in patients with NADKD are heterogenous compared with albuminuric diabetic patients and interstitial changes as well as atherosclerosis can turn out to be the main morphological finding in the absence of glomerulopathy signs. Some modern pathophysiological mechanisms proposed today for understanding of NADKD such as vascular, inflammatory, acute renal injury and use of pharmacological agents with renoprotective properties are elucidated. Contemporary data about clinical characteristics of NADKD, as well as its prognostic value, diagnostics and monitoring and its association with cardiovascular risk are given. A prognostic significance of NADKD should be defined more precisely. NADKD is shown to increase a risk of myocardial infarction and stroke development as well as a death from cardiovascular causes in patients with diabetes mellitus. An importance of the search for alternative diagnostic markers for detecting renal injury in the absence of albuminuria is emphasized. The evaluations of the markers of tubular damage and interstitial fibrosis, as well as proteomic approaches, are considered today as perspective diagnostic and prognostic options in NADKD. The study of pathogenesis, pathomorphology, clinical course of NADKD, as well as the development of approaches for an early diagnostics and treatment of this complication of diabetes mellitus are determined as the tasks for future research.&#x0D;

Drugs Targeting Mechanisms of Aging to Delay Age-Related Disease and Promote Healthspan: Proceedings of a National Institute on Aging Workshop.

The geroscience hypothesis posits that by targeting key hallmarks of aging we may simultaneously prevent or delay several age-related diseases and thereby increase healthspan, or life span spent free of significant disease and disability. Studies are underway to examine several possible pharmacological interventions for this purpose. As part of a National Institute on Aging workshop on the development of function-promoting therapies, scientific content experts provided literature reviews and state-of-the-field assessments for the studies of senolytics, nicotinamide adenine dinucleotide (NAD+) boosters, and metformin. Cellular senescence increases with age, and preclinical studies demonstrate that the use of senolytic drugs improves healthspan in rodents. Human studies using senolytics are in progress. NAD+ and its phosphorylated form, NADP+, play vital roles in metabolism and cellular signaling. Increasing NAD+ by supplementation with precursors including nicotinamide riboside and nicotinamide mononucleotide appears to extend healthspan in model organisms, but human studies are limited and results are mixed. Metformin is a biguanide widely used for glucose lowering, which is believed to have pleiotropic effects targeting several hallmarks of aging. Preclinical studies suggest it improves life span and healthspan, and observational studies suggest benefits for the prevention of several age-related diseases. Clinical trials are underway to examine metformin for healthspan and frailty prevention. Preclinical and emerging clinical studies suggest there is potential to improve healthspan through the use of pharmacologic agents reviewed. However, much further research is needed to demonstrate benefits and general safety for wider use, the appropriate target populations, and longer-term outcomes.

Brazilian guidelines for the pharmacological treatment of the pulmonary symptoms of cystic fibrosis. Official document of the Sociedade Brasileira de Pneumologia e Tisiologia (SBPT, Brazilian Thoracic Association).

Cystic fibrosis (CF) is a genetic disease that results in dysfunction of the CF transmembrane conductance regulator (CFTR) protein, which is a chloride and bicarbonate channel expressed in the apical portion of epithelial cells of various organs. Dysfunction of that protein results in diverse clinical manifestations, primarily involving the respiratory and gastrointestinal systems, impairing quality of life and reducing life expectancy. Although CF is still an incurable pathology, the therapeutic and prognostic perspectives are now totally different and much more favorable. The purpose of these guidelines is to define evidence-based recommendations regarding the use of pharmacological agents in the treatment of the pulmonary symptoms of CF in Brazil. Questions in the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) format were employed to address aspects related to the use of modulators of this protein (ivacaftor, lumacaftor+ivacaftor, and tezacaftor+ivacaftor), use of dornase alfa, eradication therapy and chronic suppression of Pseudomonas aeruginosa, and eradication of methicillin-resistant Staphylococcus aureus and Burkholderia cepacia complex. To formulate the PICO questions, a group of Brazilian specialists was assembled and a systematic review was carried out on the themes, with meta-analysis when applicable. The results obtained were analyzed in terms of the strength of the evidence compiled, the recommendations being devised by employing the GRADE approach. We believe that these guidelines represent a major advance to be incorporated into the approach to patients with CF, mainly aiming to favor the management of the disease, and could become an auxiliary tool in the definition of public policies related to CF.

SARS-CoV-2 Inhibits NRF2-Mediated Antioxidant Responses in Airway Epithelial Cells and in the Lung of a Murine Model of Infection.

Several viruses have been shown to modulate the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2), the master regulator of redox homeostasis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, also seems to disrupt the balance between oxidants and antioxidants, which likely contributes to lung damage. Using in vitro and in vivo models of infection, we investigated how SARS-CoV-2 modulates the transcription factor NRF2 and its dependent genes, as well as the role of NRF2 during SARS-CoV-2 infection. We found that SARS-CoV-2 infection downregulates NRF2 protein levels and NRF2-dependent gene expression in human airway epithelial cells and in lungs of BALB/c mice. Reductions in cellular levels of NRF2 seem to be independent of proteasomal degradation and the interferon/promyelocytic leukemia (IFN/PML) pathway. Furthermore, lack of the Nrf2 gene in SARS-CoV-2-infected mice exacerbates clinical disease, increases lung inflammation, and is associated with a trend toward increased lung viral titers, indicating that NRF2 has a protective role during this viral infection. In summary, our results suggest that SARS-CoV-2 infection alters the cellular redox balance by downregulating NRF2 and its dependent genes, which exacerbates lung inflammation and disease, therefore, suggesting that the activation of NRF2 could be explored as therapeutic approach during SARS-CoV-2 infection. IMPORTANCE The antioxidant defense system plays a major function in protecting the organism against oxidative damage caused by free radicals. COVID-19 patients often present with biochemical characteristics of uncontrolled pro-oxidative responses in the respiratory tract. We show herein that SARS-CoV-2 variants, including Omicron, are potent inhibitors of cellular and lung nuclear factor erythroid 2-related factor 2 (NRF2), the master transcription factor that controls the expression of antioxidant and cytoprotective enzymes. Moreover, we show that mice lacking the Nrf2 gene show increased clinical signs of disease and lung pathology when infected with a mouse-adapted strain of SARS-CoV-2. Overall, this study provides a mechanistic explanation for the observed unbalanced pro-oxidative response in SARS-CoV-2 infections and suggests that therapeutic strategies for COVID-19 may consider the use of pharmacologic agents that are known to boost the expression levels of cellular NRF2.

Corchorus olitorius extract exhibit anti-hyperglycemic and anti-inflammatory properties in rodent models of obesity and diabetes mellitus.

Obesity and type 2 diabetes (T2D) are chronic conditions with detrimental impacts on the overall health of individuals. Presently, the use of pharmacological agents in obesity and T2D offers limited benefits and pose side effects. This warrant studies on remedies that are less toxic and inexpensive while effective in ameliorating secondary complications in obesity and T2D. Plant-based remedies have been explored increasingly due to their remarkable properties and safety profile. We searched for pre-clinical evidence published from inception until 2023 on PubMed, Scopus, Google, and Semantic scholar on Corchorus olitorius (C. olitorius) in both obesity and T2D. Our focus was to understand the beneficial impact of this plant-based remedy on basic glycemic, lipid, inflammatory, and biomarkers of oxidative stress. The evidence gathered in this review suggests that C. olitorius treatment may significantly reduce blood glucose, body weight, total cholesterol, triglycerides, and low-density lipoprotein (LDL) in concomitant with increasing high-density lipoprotein-cholesterol (HDL-c) in rodent models of obesity and T2D. Interestingly, this effect was consistent with the reduction of malonaldehyde, superoxide dismutase and catalases, tumor necrosis factor-alpha, interleukins, and leptin. Some of the mechanisms by which C. olitorius reduces blood glucose levels is through stimulation of insulin secretion, increasing β-cell proliferation, thus promoting insulin sensitivity; the process which is mediated by ascorbic acid present in this plant. C. olitorius anti-hyperlipidemia is attributable to the content of ferulic acid found in this plant, which inhibits 3-Hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors and thus results in reduced synthesis of cholesterol and increased hepatic LDL-c receptor expression, respectively. The present review provides extensive knowledge and further highlights the potential benefits of C. olitorius on basic metabolic parameters, lipid profile, inflammation, and oxidative stress in rodent models of obesity and T2D.