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1.
Effects of oxybate dose and regimen on disrupted nighttime sleep and sleep architecture.
Roth, T, Dauvilliers, Y, Bogan, RK, Plazzi, G, Black, J
Sleep medicine. 2024;:255-265
Abstract
Many components of sleep are disrupted in patients with narcolepsy, including sleep quality, sleep architecture, and sleep stability (ie, frequent awakenings/arousals and frequent shifts from deeper to lighter stages of sleep). Sodium oxybate, dosed twice nightly, has historically been used to improve sleep, and subsequent daytime symptoms, in patients with narcolepsy. Recently, new formulations have been developed to address the high sodium content and twice-nightly dosing regimen of sodium oxybate: low-sodium oxybate and once-nightly sodium oxybate. To date, no head-to-head trials have been conducted to compare the effects of each oxybate product. This review aims to give an overview of the existing scientific literature regarding the impact of oxybate dose and regimen on sleep architecture and disrupted nighttime sleep in patients with narcolepsy. Evidence from 5 key clinical trials, as well as supporting evidence from additional studies, suggests that sodium oxybate, dosed once- and twice-nightly, is effective in improving sleep, measures of sleep architecture, and disrupted nighttime sleep in patients with narcolepsy. Direct comparison of available efficacy and safety data between oxybate products is complicated by differences in trial designs, outcomes assessed, and statistical analyses; future head-to-head trials are needed to better understand the advantage and disadvantages of each agent.
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Phytochemical Profiling and Biological Activities of Rhododendron Subsect. Ledum: Discovering the Medicinal Potential of Labrador Tea Species in the Northern Hemisphere.
Vengrytė, M, Raudonė, L
Plants (Basel, Switzerland). 2024;(6)
Abstract
Rhododendron subsect. Ledum is a distinct taxonomic subdivision within the genus Rhododendron, comprising a group of evergreen shrubs and small trees. This review will comprehensively analyse the phytochemical profiles and biological properties of the Rhododendron subsect. Ledum species subsect. Ledum consists of eight plant species indigenous to temperate and subarctic regions of the Northern Hemisphere, collectively known as Labrador tea. Recent investigations have concentrated on the phytochemical constituents of these plants due to limited data, emphasizing their evergreen nature and potential industrial significance. This review summarizes their major phytochemical constituents, including flavonoids, phenolic acids, and terpenoids, and discusses their potential biological activities, such as antioxidant, anti-inflammatory, antimicrobial, antitumor, hypoglycemic, hepatoprotective, neuroprotective, and cardioprotective effects. Traditional uses of these plant species align with scientific findings, emphasizing the significance of these plants in traditional medicine. However, despite promising results, gaps exist in our understanding of specific compounds' therapeutic effects, necessitating further research for comprehensive validation. This review serves as a valuable resource for researchers, identifying current knowledge, uncertainties, and emerging trends in the study of the Rhododendron subsect. Ledum species.
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3.
More than Just Bread and Wine: Using Yeast to Understand Inherited Cytochrome Oxidase Deficiencies in Humans.
Caron-Godon, CA, Collington, E, Wolf, JL, Coletta, G, Glerum, DM
International journal of molecular sciences. 2024;(7)
Abstract
Inherited defects in cytochrome c oxidase (COX) are associated with a substantial subset of diseases adversely affecting the structure and function of the mitochondrial respiratory chain. This multi-subunit enzyme consists of 14 subunits and numerous cofactors, and it requires the function of some 30 proteins to assemble. COX assembly was first shown to be the primary defect in the majority of COX deficiencies 36 years ago. Over the last three decades, most COX assembly genes have been identified in the yeast Saccharomyces cerevisiae, and studies in yeast have proven instrumental in testing the impact of mutations identified in patients with a specific COX deficiency. The advent of accessible genome-wide sequencing capabilities has led to more patient mutations being identified, with the subsequent identification of several new COX assembly factors. However, the lack of genotype-phenotype correlations and the large number of genes involved in generating a functional COX mean that functional studies must be undertaken to assign a genetic variant as being causal. In this review, we provide a brief overview of the use of yeast as a model system and briefly compare the COX assembly process in yeast and humans. We focus primarily on the studies in yeast that have allowed us to both identify new COX assembly factors and to demonstrate the pathogenicity of a subset of the mutations that have been identified in patients with inherited defects in COX. We conclude with an overview of the areas in which studies in yeast are likely to continue to contribute to progress in understanding disease arising from inherited COX deficiencies.
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Rhabdomyolysis caused by Botrychium ternatum intoxication: Case report and literature review.
Liu, MW, Zhang, CH, Zhang, QJ, Zhang, BR
Medicine. 2024;(9):e37304
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Abstract
RATIONALE Botrychium ternatum ((Thunb.) Sw.), a traditional Chinese medicine, is known for its therapeutic properties in clearing heat, detoxifying, cough suppression, and phlegm elimination. It has been extensively used in clinics for the treatment of many inflammation-related diseases. Currently, there are no documented cases of rhabdomyolysis resulting from Botrychium ternatum intoxication. PATIENT CONCERNS A 57-year-old male presented with a complaint of low back discomfort accompanied by tea-colored urine lasting for 4 days. The patient also exhibited markedly increased creatine phosphate kinase and myoglobin levels. Prior to the onset of symptoms, the patient consumed 50 g of Botrychium ternatum to alleviate pharyngodynia. DIAGNOSES The patient was diagnosed with rhabdomyolysis due to Botrychium ternatum intoxication. INTERVENTIONS The patient underwent a substantial volume of fluid resuscitation, diuresis, and alkalization of urine, as well as correction of the acid-base balance and electrolyte disruption. OUTCOMES Following a 10-day treatment plan involving massive fluid resuscitation, diuresis, and alkalization of urine, the patient showed notable improvement in his lower back pain and reported the absence of any discomfort. Following reexamination, the levels of creatine phosphate kinase and myoglobin were restored to within the normal ranges. Additionally, no abnormalities were detected in liver or renal function. As a result, the patient was considered eligible for discharge and was monitored. CONCLUSIONS Botrychium ternatum intoxication was associated with the development of rhabdomyolysis. To manage this condition, it is recommended that patients provide massive fluid resuscitation, diuresis, alkalization of urine, and other appropriate therapeutic interventions. LESSON Currently, there are no known cases of rhabdomyolysis resulting from Botrychium ternatum intoxication. However, it is important to consider the potential occurrence of rhabdomyolysis resulting from Botrychium ternatum intoxication when there is a correlation between the administration of Botrychium ternatum and the presence of muscular discomfort in the waist or throughout the body, along with tea-colored urine. Considering the levels of creatine phosphate kinase and myoglobin, the diagnosis or exclusion of rhabdomyolysis caused by Botrychium ternatum intoxication should be made, and suitable treatment should be administered accordingly.
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Pharmacological prevention and treatment of opioid-induced constipation in cancer patients: A systematic review and meta-analysis.
Kistemaker, KRJ, Sijani, F, Brinkman, DJ, de Graeff, A, Burchell, GL, Steegers, MAH, van Zuylen, L
Cancer treatment reviews. 2024;:102704
Abstract
BACKGROUND Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients. METHODS A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed. RESULTS Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I2 = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I2 = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I2 = 0 %; MNTX RR 3.83, 95 % CI 2.81-5.22, I2 = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates. CONCLUSIONS Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.
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New Types of Magnetic Nanoparticles for Stimuli-Responsive Theranostic Nanoplatforms.
Wang, S, Hou, Y
Advanced science (Weinheim, Baden-Wurttemberg, Germany). 2024;(8):e2305459
Abstract
Magnetic nanomaterials have played a crucial role in promoting the application of nanotechnology in the biomedical field. Although conventional magnetic nanomaterials such as iron oxide nanoparticles (NPs) are used as biosensors, drug delivery vehicles, diagnostic and treatment agents for several diseases, the persistent pursuit of high-performance technologies has prompted researchers to continuously develop new types of magnetic nanomaterials such as iron carbide NPs. Considering their potential application in biomedicine, magnetic NPs responsive to exogenous or endogenous stimuli are developed, thereby enhancing their applicability in more complex versatile scenarios. In this review, the synthesis and surface modification of magnetic NPs are focused, particularly iron carbide NPs. Subsequently, exogenous and endogenous stimuli-responsive magnetic NP-based theranostic platforms are introduced, particularly focusing on nanozyme-based technologies and magnetic NP-mediated immunotherapy, which are emerging stimuli-responsive treatments. Finally, the challenges and perspectives of magnetic NPs to accelerate future research in this field are discussed.
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PTH and the Regulation of Mesenchymal Cells within the Bone Marrow Niche.
Liu, H, Liu, L, Rosen, CJ
Cells. 2024;(5)
Abstract
Parathyroid hormone (PTH) plays a pivotal role in maintaining calcium homeostasis, largely by modulating bone remodeling processes. Its effects on bone are notably dependent on the duration and frequency of exposure. Specifically, PTH can initiate both bone formation and resorption, with the outcome being influenced by the manner of PTH administration: continuous or intermittent. In continuous administration, PTH tends to promote bone resorption, possibly by regulating certain genes within bone cells. Conversely, intermittent exposure generally favors bone formation, possibly through transient gene activation. PTH's role extends to various aspects of bone cell activity. It directly influences skeletal stem cells, osteoblastic lineage cells, osteocytes, and T cells, playing a critical role in bone generation. Simultaneously, it indirectly affects osteoclast precursor cells and osteoclasts, and has a direct impact on T cells, contributing to its role in bone resorption. Despite these insights, the intricate mechanisms through which PTH acts within the bone marrow niche are not entirely understood. This article reviews the dual roles of PTH-catabolic and anabolic-on bone cells, highlighting the cellular and molecular pathways involved in these processes. The complex interplay of these factors in bone remodeling underscores the need for further investigation to fully comprehend PTH's multifaceted influence on bone health.
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Advances in peptide-based drug delivery systems.
Guo, S, Wang, J, Wang, Q, Wang, J, Qin, S, Li, W
Heliyon. 2024;(4):e26009
Abstract
Drug delivery systems (DDSs) are designed to deliver drugs to their specific targets to minimize their toxic effects and improve their susceptibility to clearance during targeted transport. Peptides have high affinity, low immunogenicity, simple amino acid composition, and adjustable molecular size; therefore, most peptides can be coupled to drugs via linkers to form peptide-drug conjugates (PDCs) and act as active pro-drugs. PDCs are widely thought to be promising DDSs, given their ability to improve drug bio-compatibility and physiological stability. Peptide-based DDSs are often used to deliver therapeutic substances such as anti-cancer drugs and nucleic acid-based drugs, which not only slow the degradation rate of drugs in vivo but also ensure the drug concentration at the targeted site and prolong the half-life of drugs in vivo. This article provides an profile of the advancements and future development in functional peptide-based DDSs both domestically and internationally in recent years, in the expectation of achieving targeted drug delivery incorporating functional peptides and taking full advantage of synergistic effects.
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Using caffeine as a chemical means to induce flow states.
Reich, N, Mannino, M, Kotler, S
Neuroscience and biobehavioral reviews. 2024;:105577
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Abstract
Flow is an intrinsically rewarding state characterised by positive affect and total task absorption. Because cognitive and physical performance are optimal in flow, chemical means to facilitate this state are appealing. Caffeine, a non-selective adenosine receptor antagonist, has been emphasized as a potential flow-inducer. Thus, we review the psychological and biological effects of caffeine that, conceptually, enhance flow. Caffeine may facilitate flow through various effects, including: i) upregulation of dopamine D1/D2 receptor affinity in reward-associated brain areas, leading to greater energetic arousal and 'wanting'; ii) protection of dopaminergic neurons; iii) increases in norepinephrine release and alertness, which offset sleep-deprivation and hypoarousal; iv) heightening of parasympathetic high frequency heart rate variability, resulting in improved cortical stress appraisal, v) modification of striatal endocannabinoid-CB1 receptor-signalling, leading to enhanced stress tolerance; and vi) changes in brain network activity in favour of executive function and flow. We also discuss the application of caffeine to treat attention deficit hyperactivity disorder and caveats. We hope to inspire studies assessing the use of caffeine to induce flow.
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Prognostic potential of nutritional risk screening and assessment tools in predicting survival of patients with pancreatic neoplasms: a systematic review.
Yu, M, Li, X, Chen, M, Liu, L, Yao, T, Li, J, Su, W
Nutrition journal. 2024;(1):17
Abstract
BACKGROUNDS & AIMS The nutritional evaluation of pancreatic cancer (PC) patients lacks a gold standard or scientific consensus, we aimed to summarize and systematically evaluate the prognostic value of nutritional screening and assessment tools used for PC patients. METHODS Relevant studies were retrieved from major databases (PubMed, Embase, Web of Science, Cochrane Library) and searched from January 2010 to December 2023. We performed meta-analyses with STATA 14.0 when three or more studies used the same tool. RESULTS This analysis included 27 articles involving 6,060 PC patients. According to a meta-analysis of these studies, poor nutritional status evaluated using five nutritional screening tools Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk Index (GNRI), Controlling Nutritional Status Score (CONUT), Nutrition Risk Screening (NRS2002) and Glasgow Prognostic Score (GPS) was associated with all-cause mortality in PC patients. But Modified Glasgow Prognostic Score (mGPS) did not. Of all tools analyzed, CONUT had the maximum HR for mortality (HR = 1.978, 95%CI 1.345-2.907, P = 0.001). CONCLUSION All-cause mortality in PC patients was predicted by poor nutritional status. CONUT may be the best nutritional assessment tool for PC patients. The clinical application value of Short Form Mini Nutritional Assessment (MNA-SF), Generated Subjective Global Assessment (SGA) and Patient-generated Subjective Global Assessment (PG-SGA) in PC patients need to be confirmed. In order to improve patients' nutritional status and promote their recovery, nutritional screening tools can be used. REGISTRATION This systematic review was registered at the International Prospective Register of Systematic Reviews (PROSPERO) (number CRD42022376715).