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International Journal of Molecular... Jun 2024Unfractionated heparin (UFH) and its low-molecular-weight fragments (LMWH) are widely used as anticoagulants for surgical procedures and extracorporeal blood...
Unfractionated heparin (UFH) and its low-molecular-weight fragments (LMWH) are widely used as anticoagulants for surgical procedures and extracorporeal blood purification therapies such as cardiovascular surgery and dialysis. The anticoagulant effect of heparin is essential for the optimal execution of extracorporeal blood circulation. However, at the end of these procedures, to avoid the risk of bleeding, it is necessary to neutralize it. Currently, the only antidote for heparin neutralization is protamine sulphate, a highly basic protein which constitutes a further source of serious side events and is ineffective in neutralizing LMWH. Furthermore, dialysis patients, due to the routine administration of heparin, often experience serious adverse effects, among which HIT (heparin-induced thrombocytopenia) is one of the most severe. For this reason, the finding of new heparin antagonists or alternative methods for heparin removal from blood is of great interest. Here, we describe the synthesis and characterization of a set of biocompatible macroporous cryogels based on poly(2-hydroxyethyl methacrylate) (pHEMA) and -lysine with strong filtering capability and remarkable neutralization performance with regard to UFH and LMWH. These properties could enable the design and creation of a filtering device to rapidly reverse heparin, protecting patients from the harmful consequences of the anticoagulant.
Topics: Heparin; Humans; Cryogels; Anticoagulants; Lysine; Heparin, Low-Molecular-Weight; Heparin Antagonists
PubMed: 38928208
DOI: 10.3390/ijms25126503 -
BMC Plant Biology Jun 2024Microplastic (MP) pollution in terrestrial ecosystems is gaining attention, but there is limited research on its effects on leafy vegetables when combined with heavy...
Microplastic (MP) pollution in terrestrial ecosystems is gaining attention, but there is limited research on its effects on leafy vegetables when combined with heavy metals. This study examines the impact of three MP types-polyethylene (PE), polyethylene terephthalate (PET), and polystyrene (PS)-at concentrations of 0.02, 0.05, and 0.1% w/w, along with cadmium (Cd) and biochar (B), on germination, growth, nutrient absorption, and heavy metal uptake in red amaranth (Amaranthus tricolor L.). We found that different MP types and concentrations did not negatively affect germination parameters like germination rate, relative germination rate, germination vigor, relative germination vigor, and germination speed. However, they increased phytotoxicity and decreased stress tolerance compared to an untreated control (CK1). The presence of MPs, particularly the PS type, reduced phosphorus and potassium uptake while enhancing Cd uptake. For example, treatments PSCdB, PSCdB, and PSCdB increased Cd content in A. tricolor seedlings by 158%, 126%, and 44%, respectively, compared to the treatment CdB (CK2). Additionally, MP contamination led to reduced plant height, leaf dry matter content, and fresh and dry weights, indicating adverse effects on plant growth. Moreover, the presence of MPs increased bioconcentration factors and translocation factors for Cd, suggesting that MPs might act as carriers for heavy metal absorption in plants. On the positive side, the addition of biochar improved several root parameters, including root length, volume, surface area, and the number of root tips in the presence of MPs, indicating potential benefits for plant growth. Our study shows that the combination of MPs and Cd reduces plant growth and increases the risk of heavy metal contamination in food crops. Further research is needed to understand how different MP types and concentrations affect various plant species, which will aid in developing targeted mitigation strategies and in exploring the mechanisms through which MPs impact plant growth and heavy metal uptake. Finally, investigating the potential of biochar application in conjunction with other amendments in mitigating these effects could be key to addressing MP and heavy metal contamination in agricultural systems.
Topics: Amaranthus; Cadmium; Charcoal; Microplastics; Soil Pollutants; Germination; Nutrients; Seedlings
PubMed: 38926861
DOI: 10.1186/s12870-024-05312-0 -
British Journal of Clinical Pharmacology Jun 2024Bleeding events are common in patients prescribed anticoagulants and can have devastating consequences. Several specific and nonspecific agents have been developed to... (Review)
Review
Bleeding events are common in patients prescribed anticoagulants and can have devastating consequences. Several specific and nonspecific agents have been developed to reverse the effects of anticoagulant drugs or toxins. Vitamin K, as the oldest of these antidotes, specifically counteracts the effects of pharmaceuticals and rodenticides designed to deplete stores of vitamin K-dependent factors. In cases of life-threatening bleeding, the addition of prothrombin complex concentrates (PCCs) allows for the immediate replacement of coagulation factors. While the use of PCCs has been extended to the non-specific reversal of the effects of newer direct oral anticoagulants, the specific agents idarucizumab, targeting dabigatran and andexanet-α, binding factor Xa inhibitors, have recently been developed and are being preferentially recommended by most guidelines. However, despite having rapid effects on correcting coagulopathy, there is to date a lack of robust evidence establishing the clear superiority of direct oral anticoagulant-specific reversal agents over PCCs in terms of haemostatic efficacy, safety or mortality. For andexanet-α, a potential signal of increased thromboembolic risks, comparatively high costs and low availability might also limit its use, even though emerging evidence appears to bolster its role in intracranial haemorrhage. Protamine is the specific agent for the reversal of unfractionated heparin anticoagulation used mainly in cardiovascular surgery. It is much less effective for low molecular weight heparin fragments and is usually reserved for cases with life-threatening bleeding.
PubMed: 38926082
DOI: 10.1111/bcp.16142 -
Toxics May 2024From 2019 to 2020, antihistamines were found in 15% of all US drug overdose deaths, often co-administered with fentanyl, with 3.6% of overdose deaths due to... (Review)
Review
From 2019 to 2020, antihistamines were found in 15% of all US drug overdose deaths, often co-administered with fentanyl, with 3.6% of overdose deaths due to antihistamines alone. The most common antihistamine found in all these reported deaths is diphenhydramine, a ubiquitous, over-the-counter and clinically important medication. Currently, there is no antidote for diphenhydramine overdose. This review summarizes the adverse health effects and current emergency medicine treatments for diphenhydramine. Several emergency medicine case reports are reviewed, and the efficacy and outcomes of a variety of treatments are compared. The treatments reviewed include the more traditional antihistamine overdose therapeutics physostigmine and sodium bicarbonate, as well as newer ones such as donepezil, dexmedetomidine, and lipid emulsion therapy. We conclude that more study is needed to determine the ideal therapeutic approach to treating antihistamine overdoses.
PubMed: 38922056
DOI: 10.3390/toxics12060376 -
Biosensors May 2024Glucosamine-chitosan synthesized by the Maillard reaction was combined with montmorillonite to obtain a nanohybrid composite to immobilize horseradish peroxidase. The...
Glucosamine-chitosan synthesized by the Maillard reaction was combined with montmorillonite to obtain a nanohybrid composite to immobilize horseradish peroxidase. The material combines the advantageous properties of clay with those of the chitosan derivative; has improved water solubility and reduced molecular weight and viscosity; involves an eco-friendly synthesis; and exhibits ion exchange capacity, good adhesiveness, and a large specific surface area for enzyme adsorption. The physicochemical characteristics of the composite were analyzed by infrared spectroscopy and X-ray diffraction to determine clay-polycation interactions. The electrochemical response of the different polyphenols to glassy carbon electrodes modified with the composite was evaluated by cyclic voltammetry. The sensitivity and detection limit values obtained with the biosensor toward hydroquinone, chlorogenic acid, catechol, and resorcinol are (1.6 ± 0.2) × 10 µA mM and (74 ± 8) nM; (1.2 ± 0.1) × 10 µA mM and (26 ± 3) nM; (16 ± 2) µA mM and (0.74 ± 0.09) μM; and (3.7± 0.3) µA mM and (3.3 ± 0.2) μM, respectively. The biosensor was applied to quantify polyphenols in pennyroyal and lemon verbena extracts.
Topics: Bentonite; Biosensing Techniques; Polyphenols; Chitosan; Horseradish Peroxidase; Enzymes, Immobilized; Electrochemical Techniques; Glucosamine; Electrodes
PubMed: 38920582
DOI: 10.3390/bios14060278 -
Rhode Island Medical Journal (2013) Jul 2024The molecular pathogenesis of exocrine pancreatic cancer involves mutations K-RAS, TP53, CDKN2A, and SMAD4. The KRAS oncogene leads to constitutively active tumor cell... (Review)
Review
The molecular pathogenesis of exocrine pancreatic cancer involves mutations K-RAS, TP53, CDKN2A, and SMAD4. The KRAS oncogene leads to constitutively active tumor cell proliferation and is present in 90% of unresectable or metastatic pancreatic adenocarcinomas. Of these, the G12C variant of K-RAS genes accounts for 1-2% of mutations. A 65-year-old woman initially diagnosed with T3N0M0 pancreatic adenocarcinoma, underwent six cycles of neoadjuvant chemotherapy with mFOLFIRINOX followed by Whipple procedure. Her pathological stage was T4N2. She then received adjuvant mFOLFIRINOX but unfortunately her disease progressed through multiple lines of chemotherapy. Molecular analysis by Next Generation Sequence(NGS) panel revealed KRAS G12C mutation. Based on this mutational status, she was started on Sotorasib to which she had clinical response lasting for about 11 months prior to disease progression. Off-label use of Sotorasib as fourth-line treatment in our patient with KRAS G12C mutated pancreatic cancer was efficacious and relatively well tolerated.
Topics: Humans; Pancreatic Neoplasms; Female; Aged; Adenocarcinoma; Triazoles; Antineoplastic Combined Chemotherapy Protocols; Proto-Oncogene Proteins p21(ras); Pyrimidines; Mutation; Antineoplastic Agents; Irinotecan; Oxaliplatin; Fluorouracil; Leucovorin; Off-Label Use; Piperazines; Pyridines
PubMed: 38917307
DOI: No ID Found -
BioRxiv : the Preprint Server For... Jun 2024Toxin-antidote systems are selfish genetic elements composed of a linked toxin and antidote. The toxin-antidote system in consists of a transmembrane toxin protein...
Toxin-antidote systems are selfish genetic elements composed of a linked toxin and antidote. The toxin-antidote system in consists of a transmembrane toxin protein PEEL-1 which acts cell autonomously to kill cells. Here we investigate the molecular mechanism of PEEL-1 toxicity. We find that PEEL-1 requires a small membrane protein, PMPL-1, for toxicity. Together, PEEL-1 and PMPL-1 are sufficient for toxicity in a heterologous system, HEK293T cells, and cause cell swelling and increased cell permeability to monovalent cations. Using purified proteins, we show that PEEL-1 and PMPL-1 allow ion flux through lipid bilayers and generate currents which resemble ion channel gating. Our work suggests that PEEL-1 kills cells by co-opting PMPL-1 and creating a cation channel.
PubMed: 38915716
DOI: 10.1101/2024.06.11.598564 -
Scientific Reports Jun 2024Deliberate open burning of crop residues emits greenhouse gases and toxic pollutants into the atmosphere. This study investigates the environmental impacts (global...
Deliberate open burning of crop residues emits greenhouse gases and toxic pollutants into the atmosphere. This study investigates the environmental impacts (global warming potential, GWP) and economic impacts (net cash flow) of nine agricultural residue management schemes, including open burning, fertilizer production, and biochar production for corn residue, rice straw, and sugarcane leaves. The environmental assessment shows that, except the open burning schemes, fossil fuel consumption is the main contributor of the GWP impact. The fertilizer and biochar schemes reduce the GWP impact including black carbon by 1.88-1.96 and 2.46-3.22 times compared to open burning. The biochar schemes have the lowest GWP (- 1833.19 to - 1473.21 kg CO-eq/ton). The economic assessment outcomes reveal that the biochar schemes have the highest net cash flow (222.72-889.31 US$/ton or 1258.15-13409.16 US$/ha). The expenditures of open burning are practically zero, while the biochar schemes are the most costly to operate. The most preferable agricultural residue management type is the biochar production, given the lowest GWP impact and the highest net cash flow. To discourage open burning, the government should tailor the government assistance programs to the needs of the farmers and make the financial assistance more accessible.
Topics: Crops, Agricultural; Agriculture; Charcoal; Global Warming; Fertilizers; Zea mays; Oryza; Open Waste Burning
PubMed: 38909099
DOI: 10.1038/s41598-024-65389-3 -
BMC Complementary Medicine and Therapies Jun 2024This study explores the medicinal plant knowledge of the Baiku Yao, a unique ethnic group in China. Despite existing research on their ethnobotanical practices, a...
BACKGROUND
This study explores the medicinal plant knowledge of the Baiku Yao, a unique ethnic group in China. Despite existing research on their ethnobotanical practices, a comprehensive understanding of their medicinal flora remains lacking. This study aims to document and analyze the species distribution, utilization, and traditional knowledge of medicinal plants used by Baiku Yao.
METHODS
Ethnobotanical surveys were conducted in various Baiku Yao villages across different seasons from 2019 to 2023. Informants were interviewed, and plant specimens were collected and identified. Statistical analyses, including the Relative Frequency of Citation (RFC), were employed to understand plant importance in Baiku Yao culture.
RESULTS
In an ethnobotanical survey conducted in the Baiku Yao region, 434 medicinal plant species were documented, highlighting significant ethnobotanical diversity and a deep cultural integration of traditional medicinal practices. The study revealed pronounced geographical variations in plant knowledge among villages, with a notable reliance on wild plants, as 85.48% were sourced from the wild, reflecting unique local ethnobotanical knowledge. Predominantly herbs and shrubs were used due to their accessibility and abundance in the local environment. High Relative Frequency of Citation (RFC) values for certain species underscored their importance for local health needs and additional economic value. The utilization of various plant parts, particularly whole plants, roots, and leaves, indicates a holistic approach to medicinal applications, adapted to combat prevalent health issues such as skin and infectious diseases. The study also uncovered the Baiku Yao's cultural practices for countering "Gu" afflictions-a range of pathogenic conditions-with 18 diverse antidote plants used for skin, digestive, and musculoskeletal disorders. The study underscores the imperative of preserving this rich medicinal heritage through innovative models that engage youth and leverage new media, ensuring the inheritance and evolution of Baiku Yao's traditional knowledge.
CONCLUSIONS
Baiku Yao's medicinal plant use reflects a deep, culturally ingrained knowledge, closely tied to local ecology. The study highlights the importance of preserving this unique ethnobotanical heritage and suggests interdisciplinary approaches for future research.
Topics: Humans; China; Ethnicity; Ethnobotany; Health Knowledge, Attitudes, Practice; Medicine, Chinese Traditional; Plants, Medicinal; Surveys and Questionnaires
PubMed: 38907195
DOI: 10.1186/s12906-024-04545-8