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Molecules (Basel, Switzerland) Dec 2021Neuropathic pain is a refractory disease that occurs across the world and pharmacotherapy has limited efficacy and/or safety. This disease imposes a significant burden... (Review)
Review
Neuropathic pain is a refractory disease that occurs across the world and pharmacotherapy has limited efficacy and/or safety. This disease imposes a significant burden on both the somatic and mental health of patients; indeed, some patients have referred to neuropathic pain as being 'worse than death'. The pharmacological agents that are used to treat neuropathic pain at present can produce mild effects in certain patients, and induce many adverse reactions, such as sedation, dizziness, vomiting, and peripheral oedema. Therefore, there is an urgent need to discover novel drugs that are safer and more effective. Natural compounds from medical plants have become potential sources of analgesics, and evidence has shown that glycosides alleviated neuropathic pain via regulating oxidative stress, transcriptional regulation, ion channels, membrane receptors and so on. In this review, we summarize the epidemiology of neuropathic pain and the existing therapeutic drugs used for disease prevention and treatment. We also demonstrate how glycosides exhibit an antinociceptive effect on neuropathic pain in laboratory research and describe the antinociceptive mechanisms involved to facilitate the discovery of new drugs to improve the quality of life of patients experiencing neuropathic pain.
Topics: Analgesics; Animals; Biomarkers; Disease Models, Animal; Disease Susceptibility; Gene Expression Regulation; Glycosides; Humans; Ion Channel Gating; Mice; Neuralgia; Oxidative Stress; Pain Management; Structure-Activity Relationship; Treatment Outcome
PubMed: 35011486
DOI: 10.3390/molecules27010255 -
Work (Reading, Mass.) 2022Hotel room cleaners are disproportionately exposed to hazards that increase risk for poor health outcomes. Interventions are needed to improve the health of these...
BACKGROUND
Hotel room cleaners are disproportionately exposed to hazards that increase risk for poor health outcomes. Interventions are needed to improve the health of these workers. Yet we know little about the expressed needs of hotel room cleaners nor do we know about managers' perspectives on how to best optimize employee health.
OBJECTIVE
We aimed to develop an understanding of perceived intervention needs among hotel room cleaners and to assess managers' views on the acceptability of the proposed interventions.
METHODS
We used a community-based approach to recruit study participants. We conducted five focus groups among hotel room cleaners and individual interviews with hotel managers. Interviews were audio-recorded, transcribed, and analyzed using content analysis.
RESULTS
The workers expressed needs centered on pay, workload, appreciation, ergonomics, chemical and biological hazards, nutrition, smoking cessation, exercise, mental health and stress management. In addition to echoing the workers' expressed needs, managers emphasized employee retention and financial literacy.
CONCLUSIONS
To our knowledge, this is the first paper to include both workers' and managers' accounts on intervention approaches that will optimize health and wellbeing. This paper offers a guide for future program development among hospitality workers. Effective interventions need to be integrated, encompassing the individual, intrapersonal, organizational, and policy levels.
Topics: Ergonomics; Focus Groups; Humans; Mental Health; Occupational Health; Workload
PubMed: 35253670
DOI: 10.3233/WOR-205060 -
Haematologica Nov 2019Chemoimmunotherapy has been the standard of care for patients with chronic lymphocytic leukemia for a long time. However, over the last few years, novel agents have... (Review)
Review
Chemoimmunotherapy has been the standard of care for patients with chronic lymphocytic leukemia for a long time. However, over the last few years, novel agents have produced unprecedented outcomes in treatment-naïve and relapsed/refractory chronic lymphocytic leukemia. With the advent of these targeted agents, treatment options have diversified very considerably and new questions have emerged. For example, it is unclear whether these novel agents should be used as sequential monotherapies until disease progression or whether they should preferably be combined in time-limited treatment regimens aimed at achieving deep and durable remissions. While both approaches yield high response rates and long progression-free and overall survival, it remains challenging to identify patients individually for the optimal concept. This review provides guidance in this decision process by presenting evidence on sequential and combined use of novel agents and discussing the advantages and drawbacks of these two approaches.
Topics: Algorithms; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Molecular Targeted Therapy; Treatment Outcome
PubMed: 31585959
DOI: 10.3324/haematol.2018.208603 -
Blood Reviews Mar 2021Clonal hematopoiesis (CH) describes somatic mutations in hematopoietic stem and progenitor cells resulting in clonal expansion in individuals with no overt hematologic... (Review)
Review
Clonal hematopoiesis (CH) describes somatic mutations in hematopoietic stem and progenitor cells resulting in clonal expansion in individuals with no overt hematologic disease. Since CH increases in an age-related manner, understanding its role in hematopoietic cell transplantation (HCT) has become increasingly relevant to an aging transplant population. Multiple factors distinguish post-transplant hematopoiesis from unperturbed, steady-state hematopoiesis, including the influence of immunosuppressants, cytotoxic reagents, and marked proliferative stress, all of which may enhance or diminish the opportunity for clonal expansion. We reviewed the available clinical evidence on the consequences of CH at time of transplant in patients undergoing autologous HCT, and the impact of donor and recipient CH on allogeneic HCT outcomes. In the absence of evidence-based guidelines, we share our suggestions for managing donors and recipients found to have CH. Large-scale studies are needed to guide an evidence-based, uniform approach for the management of CH in the setting of HCT.
Topics: Clinical Decision-Making; Clonal Hematopoiesis; Disease Management; Disease Progression; Graft vs Host Disease; Hematologic Diseases; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Prognosis; Tissue Donors; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome
PubMed: 32896435
DOI: 10.1016/j.blre.2020.100744 -
Journal of the American Heart... Jun 2021Pulmonary hypertension (PH) attributable to left heart disease (LHD) is believed to be the most common form of PH and is strongly associated with increased mortality and... (Review)
Review
Pulmonary hypertension (PH) attributable to left heart disease (LHD) is believed to be the most common form of PH and is strongly associated with increased mortality and morbidity in this patient population. Specific therapies for PH-LHD have not yet been identified and the use of pulmonary artery hypertension-targeted therapies in PH-LHD are not recommended. Endothelin receptor antagonists, phosphodiesterase-5 inhibitors, guanylate cyclase stimulators, and prostacyclins have all been studied in PH-LHD with conflicting results. Understanding the mechanisms underlying PH-LHD could potentially provide novel therapeutic targets. Fibrosis, oxidative stress, and metabolic syndrome have been proposed as pathophysiological components of PH-LHD. Genetic associations have also been identified, offering additional mechanisms with biological plausibility. This review summarizes the evidence and challenges for treatment of PH-LHD and focuses on underlying mechanisms on the horizon that could develop into potential therapeutic targets for this disease.
Topics: Disease Management; Endothelin Receptor Antagonists; Guanylate Cyclase; Humans; Hypertension, Pulmonary; Oxidative Stress; Phosphodiesterase 5 Inhibitors; Prognosis; Pulmonary Wedge Pressure; Ventricular Dysfunction, Left; Ventricular Function, Left
PubMed: 34032129
DOI: 10.1161/JAHA.120.020633 -
International Journal of Molecular... Apr 2020Over 10% of the global population suffers from kidney disease. However, only kidney replacement therapies, which burden medical expenses, are currently effective in... (Review)
Review
Over 10% of the global population suffers from kidney disease. However, only kidney replacement therapies, which burden medical expenses, are currently effective in treating kidney disease. Therefore, elucidating the complicated molecular pathology of kidney disease is an urgent priority for developing innovative therapeutics for kidney disease. Recent studies demonstrated that intertwined renal vasculature often causes ischemia-reperfusion injury (IRI), which generates oxidative stress, and that the accumulation of oxidative stress is a common pathway underlying various types of kidney disease. We reported that activating the antioxidative transcription factor Nrf2 in renal tubules in mice with renal IRI effectively mitigates tubular damage and interstitial fibrosis by inducing the expression of genes related to cytoprotection against oxidative stress. Additionally, since the kidney performs multiple functions beyond blood purification, renoprotection by Nrf2 activation is anticipated to lead to various benefits. Indeed, our experiments indicated the possibility that Nrf2 activation mitigates anemia, which is caused by impaired production of the erythroid growth factor erythropoietin from injured kidneys, and moderates organ damage worsened by anemic hypoxia. Clinical trials investigating Nrf2-activating compounds in kidney disease patients are ongoing, and beneficial effects are being obtained. Thus, Nrf2 activators are expected to emerge as first-in-class innovative medicine for kidney disease treatment.
Topics: Animals; Animals, Genetically Modified; Clinical Trials as Topic; Disease Management; Disease Models, Animal; Disease Susceptibility; Gene Expression Regulation; Humans; Kidney; Kidney Diseases; NF-E2-Related Factor 2; Oxidative Stress; Patient Outcome Assessment; Signal Transduction
PubMed: 32331329
DOI: 10.3390/ijms21082951 -
Open Biology Jun 2021The COVID-19 pandemic has wreaked unprecedented societal havoc worldwide. The infected individuals may present mild to severe symptoms, with nearly 20% of the confirmed... (Review)
Review
The COVID-19 pandemic has wreaked unprecedented societal havoc worldwide. The infected individuals may present mild to severe symptoms, with nearly 20% of the confirmed patients impaired with significant complications, including multi-organ failure. Acute respiratory distress imposed by SARS-CoV-2 largely results from an aggravated cytokine storm and deregulated immune response. The forkhead box O (FoxO) transcription factors are reported to play a significant role in maintaining normal cell physiology by regulating survival, apoptosis, oxidative stress, development and maturation of T and B lymphocytes, secretion of inflammatory cytokines, etc. We propose a potent anti-inflammatory approach based on activation of the FoxO as an attractive strategy against the novel coronavirus. This regime will be focused on restoring redox and inflammatory homeostasis along with repair of the damaged tissue, activation of lymphocyte effector and memory cells. Repurposing FoxO activators as a means to alleviate the inflammatory burst following SARS-CoV-2 infection can prove immensely valuable in the ongoing pandemic and provide a reliable groundwork for enriching our repertoire of antiviral modalities for any such complication in the future. Altogether, our review highlights the possible efficacy of FoxO activation as a novel arsenal for clinical management of COVID-19.
Topics: Biomarkers; COVID-19; Cytokines; Disease Management; Disease Susceptibility; Drug Discovery; Forkhead Transcription Factors; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Inflammation; Inflammation Mediators; Molecular Targeted Therapy; Oxidation-Reduction; SARS-CoV-2; Signal Transduction; COVID-19 Drug Treatment
PubMed: 34102081
DOI: 10.1098/rsob.210069 -
Molecules (Basel, Switzerland) Jul 2021In this review, a timeline starting at the willow bark and ending in the latest discoveries of analgesic and anti-inflammatory drugs will be discussed. Furthermore, the... (Review)
Review
In this review, a timeline starting at the willow bark and ending in the latest discoveries of analgesic and anti-inflammatory drugs will be discussed. Furthermore, the chemical features of the different small organic molecules that have been used in pain management will be studied. Then, the mechanism of different types of pain will be assessed, including neuropathic pain, inflammatory pain, and the relationship found between oxidative stress and pain. This will include obtaining insights into the cyclooxygenase action mechanism of nonsteroidal anti-inflammatory drugs (NSAID) such as ibuprofen and etoricoxib and the structural difference between the two cyclooxygenase isoforms leading to a selective inhibition, the action mechanism of pregabalin and its use in chronic neuropathic pain, new theories and studies on the analgesic action mechanism of paracetamol and how changes in its structure can lead to better characteristics of this drug, and cannabinoid action mechanism in managing pain through a cannabinoid receptor mechanism. Finally, an overview of the different approaches science is taking to develop more efficient molecules for pain treatment will be presented.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Calcium Channel Blockers; Cannabinoids; Drug Discovery; Humans; Neuralgia; Pain Management
PubMed: 34279369
DOI: 10.3390/molecules26134029 -
International Journal of Molecular... Jan 2022Chronic kidney disease (CKD) refers to the phenomenon of progressive decline in the glomerular filtration rate accompanied by adverse consequences, including fluid... (Review)
Review
Chronic kidney disease (CKD) refers to the phenomenon of progressive decline in the glomerular filtration rate accompanied by adverse consequences, including fluid retention, electrolyte imbalance, and an increased cardiovascular risk compared to those with normal renal function. The triggers for the irreversible renal function deterioration are multifactorial, and diabetes mellitus serves as a major contributor to the development of CKD, namely diabetic kidney disease (DKD). Recently, epigenetic dysregulation emerged as a pivotal player steering the progression of DKD, partly resulting from hyperglycemia-associated metabolic disturbances, rising oxidative stress, and/or uncontrolled inflammation. In this review, we describe the major epigenetic molecular mechanisms, followed by summarizing current understandings of the epigenetic alterations pertaining to DKD. We highlight the epigenetic regulatory processes involved in several crucial renal cell types: Mesangial cells, podocytes, tubular epithelia, and glomerular endothelial cells. Finally, we highlight epigenetic biomarkers and related therapeutic candidates that hold promising potential for the early detection of DKD and the amelioration of its progression.
Topics: Animals; Biomarkers; DNA Methylation; Diabetic Nephropathies; Disease Management; Disease Susceptibility; Epigenesis, Genetic; Extracellular Matrix; Gene Expression Regulation; Histones; Humans; Mesangial Cells; Organ Specificity; Podocytes; RNA, Untranslated
PubMed: 35055027
DOI: 10.3390/ijms23020843 -
International Journal of Molecular... Jun 2021Atherosclerosis has complex pathogenesis, which involves at least three serious aspects: inflammation, lipid metabolism alterations, and endothelial injury. There are no... (Review)
Review
Atherosclerosis has complex pathogenesis, which involves at least three serious aspects: inflammation, lipid metabolism alterations, and endothelial injury. There are no effective treatment options, as well as preventive measures for atherosclerosis. However, this disease has various severe complications, the most severe of which is cardiovascular disease (CVD). It is important to note, that CVD is among the leading causes of death worldwide. The renin-angiotensin-aldosterone system (RAAS) is an important part of inflammatory response regulation. This system contributes to the recruitment of inflammatory cells to the injured site and stimulates the production of various cytokines, such as IL-6, TNF-a, and COX-2. There is also an association between RAAS and oxidative stress, which is also an important player in atherogenesis. Angiotensin-II induces plaque formation at early stages, and this is one of the most crucial impacts on atherogenesis from the RAAS. Importantly, while stimulating the production of ROS, Angiotensin-II at the same time decreases the generation of NO. The endothelium is known as a major contributor to vascular function. Oxidative stress is the main trigger of endothelial dysfunction, and, once again, links RAAS to the pathogenesis of atherosclerosis. All these implications of RAAS in atherogenesis lead to an explicable conclusion that elements of RAAS can be promising targets for atherosclerosis treatment. In this review, we also summarize the data on treatment approaches involving cytokine targeting in CVD, which can contribute to a better understanding of atherogenesis and even its prevention.
Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Atherosclerosis; Biomarkers; Cardiovascular Diseases; Clinical Trials as Topic; Disease Management; Disease Susceptibility; Drug Evaluation, Preclinical; Endothelium; Humans; Molecular Targeted Therapy; Oxidative Stress; Reactive Oxygen Species; Renin-Angiotensin System
PubMed: 34206708
DOI: 10.3390/ijms22136702