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Bioorganic Chemistry Dec 2023The opioids have been used for more than a thousand years and are not only the most widely prescribed drugs for moderate to severe pain and acute pain, but also the... (Review)
Review
The opioids have been used for more than a thousand years and are not only the most widely prescribed drugs for moderate to severe pain and acute pain, but also the preferred drugs. However, their non-analgesic effects, especially respiratory depression and potential addiction, are important factors that plague the safety of clinical use and are an urgent problem for pharmacological researchers to address. Current research on analgesic drugs has evolved into different directions: de-opioidization; application of pharmacogenomics to individualize the use of opioids; development of new opioids with less adverse effects. The development of new opioid drugs remains a hot research topic, and with the in-depth study of opioid receptors and intracellular signal transduction mechanisms, new research ideas have been provided for the development of new opioid analgesics with less side effects and stronger analgesic effects. The development of novel opioid drugs in turn includes selective opioid receptor ligands, biased opioid receptor ligands, and multi-target opioid receptor ligands and positive allosteric modulators (PAMs) or antagonists and the single compound as multi-targeted agnoists/antagonists for different receptors. PAMs strategies are also getting newer and are the current research hotspots, including the BMS series of compounds and others, which are extensive and beyond the scope of this review. This review mainly focuses on the selective/biased/multi-targeted MOR/DOR/KOR (mu opioid receptor/delta opioid receptor/kappa opioid receptor) small molecule ligands and involves some cryo-electron microscopy (cryoEM) and structure-based approaches as well as the single compound as multi-targeted agnoists/antagonists for different receptors from 2019 to 2022, including discovery history, activities in vitro and vivo, and clinical studies, in an attempt to provide ideas for the development of novel opioid analgesics with fewer side effects.
Topics: Analgesics, Opioid; Receptors, Opioid, kappa; Receptors, Opioid, mu; Cryoelectron Microscopy; Analgesics; Ligands
PubMed: 37797454
DOI: 10.1016/j.bioorg.2023.106869 -
AIMS Microbiology 2023Two approaches are applied to studies of the phylogeny of the plague microbe , i.e., the reconstruction of its history: Molecular genetic (MG) and ecological (ECO). The... (Review)
Review
Two approaches are applied to studies of the phylogeny of the plague microbe , i.e., the reconstruction of its history: Molecular genetic (MG) and ecological (ECO). The MG approach dominates. Phylogenies created with MG and ECO methods are not congruent. MG conclusions contradict the known facts and patterns of ecology, biogeography, paleontology, etc. We discuss some obvious contradictions and inconsistencies and suggest that real phylogenies of the plague microbe can be constructed only on the basis of the integration of MG and ECO approaches.
PubMed: 38173967
DOI: 10.3934/microbiol.2023036 -
MBio Oct 2023are responsible for significant disease burden in humans, ranging from recurrent disease outbreaks (yersiniosis) to pandemics ( plague). Together with rising antibiotic...
are responsible for significant disease burden in humans, ranging from recurrent disease outbreaks (yersiniosis) to pandemics ( plague). Together with rising antibiotic resistance rates, there is a critical need to better understand pathogenesis and host immune mechanisms, as this information will aid in developing improved immunomodulatory therapeutics. Inflammasome responses in human cells are less studied relative to murine models of infection, though recent studies have uncovered key differences in inflammasome responses between mice and humans. Here, we dissect human intestinal epithelial cell and macrophage inflammasome responses to . Our findings provide insight into species- and cell type-specific differences in inflammasome responses to .
Topics: Humans; Animals; Mice; Yersinia; Inflammasomes; Yersinia pestis; Yersinia pseudotuberculosis; Plague
PubMed: 37615436
DOI: 10.1128/mbio.01310-23 -
The American Journal of Tropical... Nov 2023In rural Uganda, many people who are ill consult traditional healers prior to visiting the formal healthcare system. Traditional healers provide supportive care for...
In rural Uganda, many people who are ill consult traditional healers prior to visiting the formal healthcare system. Traditional healers provide supportive care for common illnesses, but their care may delay diagnosis and management of illnesses that can increase morbidity and mortality, hinder early detection of epidemic-prone diseases, and increase occupational risk to traditional healers. We conducted open-ended, semi-structured interviews with a convenience sample of 11 traditional healers in the plague-endemic West Nile region of northwestern Uganda to assess their knowledge, practices, and attitudes regarding plague and the local healthcare system. Most were generally knowledgeable about plague transmission and its clinical presentation and expressed willingness to refer patients to the formal healthcare system. We initiated a public health outreach program to further improve engagement between traditional healers and local health centers to foster trust in the formal healthcare system and improve early identification and referral of patients with plaguelike symptoms, which can reflect numerous other infectious and noninfectious conditions. During 2010-2019, 65 traditional healers were involved in the outreach program; 52 traditional healers referred 788 patients to area health centers. The diagnosis was available for 775 patients; malaria (37%) and respiratory tract infections (23%) were the most common diagnoses. One patient had confirmed bubonic plague. Outreach to improve communication and trust between traditional healers and local healthcare settings may result in improved early case detection and intervention not only for plague but also for other serious conditions.
Topics: Humans; Uganda; Traditional Medicine Practitioners; Plague; Delivery of Health Care; Referral and Consultation; Medicine, African Traditional
PubMed: 37783460
DOI: 10.4269/ajtmh.23-0101 -
Microorganisms Jan 2024Crayfish plague is a devastating disease of European freshwater crayfish and is caused by the oomycete (), believed to have been introduced to Europe around 1860. All... (Review)
Review
Crayfish plague is a devastating disease of European freshwater crayfish and is caused by the oomycete (), believed to have been introduced to Europe around 1860. All European species of freshwater crayfish are susceptible to the disease, including the white-clawed crayfish . is primarily spread by North American crayfish species and can also disperse rapidly through contaminated wet gear moved between water bodies. This spread, coupled with competition from non-indigenous crayfish, has drastically reduced and fragmented native crayfish populations across Europe. Remarkably, the island of Ireland remained free from the crayfish plague pathogen for over 100 years, providing a refuge for . However, this changed in 1987 when a mass mortality event was linked to the pathogen, marking its introduction to the region. Fortunately, crayfish plague was not detected again in Ireland until 2015 when a molecular analysis linked a mass mortality event in the Erne catchment to Since then, the pathogen has appeared across the island. Between 2015 and 2023, was detected in 18 water catchments, revealing multiple genotypes. Intriguingly, the pathogen in Ireland is present without its natural host species. The uneven distribution of various genetic lineages strongly suggests the human-mediated transport of zoospores via contaminated water equipment as a primary cause of spread. This review details the timeline of these events, introduction into Ireland, and its rapid spread. As well, this review references the genotypes that have been determined, and discusses the issue of non-indigenous crayfish species in Ireland and management efforts.
PubMed: 38257929
DOI: 10.3390/microorganisms12010102 -
Heliyon Nov 2023With the development of society and changes in lifestyle, major depressive disorder (MDD) has become a significant disease that plagues many people. Licorice, an... (Review)
Review
With the development of society and changes in lifestyle, major depressive disorder (MDD) has become a significant disease that plagues many people. Licorice, an excellent natural medicine with a long history of cultivation and application, is found in classical antidepressant prescriptions such as Chaihu Shugan Powder, Ganmai Dazao Decoction, Suanzaoren Decoction, etc. Licorice mainly contains triterpenoids and flavonoids, among which licorice total flavonoids (LF) and liquiritin are the main active components with good antidepressant effects. The pharmacological effects of licorice have been extensively investigated in current studies. However, a review of the antidepressant effects of LF and liquiritin has not been conducted. This article reviews the antidepressant effects of LF and liquiritin, including the biological characteristics of licorice and the pharmacological mechanism of LF and liquiritin in treating MDD. Studies have shown that LF and liquiritin can exert their antidepressant effects by improving depressive behavior, regulating endocrine and hypothalamic-pituitary-adrenal (HPA) axis function, affecting the brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) signaling pathway, enhancing synaptic plasticity, increasing monoamine neurotransmitter levels, protecting nerve cells, reducing inflammation, preventing apoptosis, reducing oxidation and other ways. This lays a theoretical foundation for the development of antidepressant drugs.
PubMed: 38074876
DOI: 10.1016/j.heliyon.2023.e22251 -
Przeglad Epidemiologiczny Jun 2024Zoonoses, diseases transmitted from animals to humans, continue to challenge public health despite advancements in controlling infectious diseases. The intricate link... (Review)
Review
Zoonoses, diseases transmitted from animals to humans, continue to challenge public health despite advancements in controlling infectious diseases. The intricate link between human, animal, and environmental health is emphasised by the fact that zoonoses contribute to 60% of emerging human infections. Wet markets, wildlife hunting, intensive wildlife farming, and interactions between domestic animals and humans are key transmission sources. Historical examples like the bubonic plague and English Sweats illustrate the longstanding impact of zoonotic diseases. With new transmission patterns emerging, it is necessary to use new techniques to predict disease spread. This article delves into the emergence of new zoonoses, such as the Nipah virus and the SARS-CoV-2 pandemic, emphasizing the importance of understanding zoonotic aspects for outbreak prevention. Re-emerging zoonoses, like tuberculosis and vaccine-preventable diseases, present challenges, exacerbated by factors like globalized human activities and disruptions caused by the COVID-19 pandemic. Public health implications are explored, including economic losses, antibiotic resistance, and the disruption of international trade.
Topics: Humans; Animals; Zoonoses; COVID-19; Public Health; SARS-CoV-2; Communicable Diseases, Emerging; Pandemics
PubMed: 38904313
DOI: 10.32394/pe/188161 -
Cureus Sep 2023Irritable bowel syndrome (IBS) plagues nearly a fifth of the general population. It is a chronic illness that can significantly lower quality of life (QoL) and work... (Review)
Review
Irritable bowel syndrome (IBS) plagues nearly a fifth of the general population. It is a chronic illness that can significantly lower quality of life (QoL) and work productivity. The relationship between diet and the functional gastrointestinal (GI) symptoms present in IBS is gaining more and more attention. In addition to being a factor in the pathophysiology of IBS, diet also has a significant impact on symptoms and overall well-being. Recent research has also shown that short-chain fermentable carbohydrates increase colonic gas production and small intestine water volume, which in turn causes functional GI symptoms in those with visceral hypersensitivity. This review article has consolidated various studies highlighting the association between certain foods and the pathophysiology of IBS. It has also talked about how restricting certain food items from the diet of affected individuals can relieve symptoms and in some cases can be more effective than pharmacotherapy. Although the low reduced fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet (LFD) is a well-known method of treating IBS symptoms, over a third of individuals do not benefit from it. This article has also discussed the effectiveness and applicability of the LFD compared to other dietary therapies for the long-term management of IBS.
PubMed: 37846263
DOI: 10.7759/cureus.45279 -
Neurotherapeutics : the Journal of the... Oct 2023The use of animal models in pre-clinical research has significantly broadened our understanding of the pathologies that underlie traumatic brain injury (TBI)-induced... (Review)
Review
The use of animal models in pre-clinical research has significantly broadened our understanding of the pathologies that underlie traumatic brain injury (TBI)-induced damage and deficits. However, despite numerous pre-clinical studies reporting the identification of promising neurotherapeutics, translation of these therapies to clinical application has so far eluded the TBI research field. A concerted effort to address this lack of translatability is long overdue. Given the inherent heterogeneity of TBI and the replication crisis that continues to plague biomedical research, this is a complex task that will require a multifaceted approach centered around rigor and reproducibility. Here, we discuss the role of three primary focus areas for better aligning pre-clinical research with clinical TBI management. These focus areas are (1) reporting and standardization of protocols, (2) replication of prior knowledge including the confirmation of expected pharmacodynamics, and (3) the broad application of open science through inter-center collaboration and data sharing. We further discuss current efforts that are establishing the core framework needed for successfully addressing the translatability crisis of TBI.
Topics: Animals; Reproducibility of Results; Brain Injuries, Traumatic; Brain Injuries; Biomedical Research
PubMed: 37525025
DOI: 10.1007/s13311-023-01400-5