anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
PURPOSE:To prepare a refreshing drink free from peculiar taste and fragrance and dispersion of the taste of product, by heat-treating a bracket fungus of the genus Fomes cultivated in a darkroom, adding it to a seasoning solution. CONSTITUTION:A bracket fungus of the genus Fomes is cultivated in a darkroom, collected in a state where the growth of the velum is prevented, the stem part is grown almost straight, the lignification is not advanced too much, and the mushroom is soft. The mushroom is treated with hot water at >=70 deg.C for about 10min so that it is sterilized and fixed. The sterilized mushroom is added to a container such as a bottle, one mushroom to one bottle or several mushroom to one bottle depending upon its length. A seasoning solution having a proper taste by the treated solution used in the above-mentioned hot water treatment, a sweetening agent, spices, coloring matter such as extracted solution of preferably safflower, etc., vitamin, mineral, etc. is added to the bottle. When a carbonated drink is obtained, carbon dioxide gas is sealed in the drink at this stage, and sterilized at about 90 deg.C for 20-30min.
PURPOSE: To obtain the subject compd. in a good yield by an one-pot process cyclizing an aminoacrylic acid ester derived from an acid halide under heating and reacting the obtained by cyclic compd. with a heterocyclic compd. to obtain a 3-quinolonecarboxylic acid deriv. and neutralizing this deriv. to precipitate the same.  
     CONSTITUTION: An acid halide represented by formula I (wherein X 1  is H, a halogen, NH 2  or CH 3 ; Hal, X 2  and X 3  are each F or Cl; and A is CH, CF, CCl, C-OCH 3  or C-CH 3 ) and a dimethylaminoacrylic acid ester represented by the formula; (CH 3 ) 2 N-CH=CH-COOR (wherein R is a 1-3C alkyl or the like) are reacted to obtain a reaction product which is, in turn, reacted with an amino represented by the formula; R 1 NH 2  to obtain a compd. represented by formula II or the compd. represented by the formula I is reacted with an aminoacrylic acid ester represented by the formula; R 1 NH-CH=CH-COOR to directly obtain the compd. represented by the formula II. Subsequently, the obtained compd. is heated in the presence of a base and cyclized to obtain a compd. represented by formula III. Next, a compd. represented by formula IV (wherein R' and R" form a monocyclic or dicyclic heterocycle) is reacted with this compd. to obtain an ester represented by formula V and this ester is hydrolyzed to be neutralized to obtain a compd. represented by formula VI as a precipitate. This compd. is useful as a strong antibacterial agent. 
     COPYRIGHT: (C)1995,JPO
High concentrations of urinary calcium counteract vasopressin action via the activation of the Calcium-Sensing Receptor (CaSR) expressed in the luminal membrane of the collecting duct cells, which impairs the trafficking of aquaporin-2 (AQP2). In line with these findings, we provide evidence that, with respect to wild-type mice, CaSR knock-in (KI) mice mimicking autosomal dominant hypocalcaemia, display a significant decrease in the total content of AQP2 associated with significantly higher levels of AQP2 phosphorylation at Ser261, a phosphorylation site involved in AQP2 degradation. Interestingly, KI mice also had significantly higher levels of phosphorylated p38MAPK, a downstream effector of CaSR and known to phosphorylate AQP2 at Ser261. Moreover, ATF1 phosphorylated at Ser63, a transcription factor downstream of p38MAPK, was significantly higher in KI. In addition, KI mice had significantly higher levels of AQP2-targeting miRNA137 consistent with a post-transcriptional downregulation of AQP2. In vivo treatment of KI mice with the calcilytic JTT-305, a CaSR antagonist, increased AQP2 expression and reduced AQP2-targeting miRNA137 levels in KI mice. Together, these results provide direct evidence for a critical role of CaSR in impairing both short-term vasopressin response by increasing AQP2-pS261, as well as AQP2 abundance, via the p38MAPK-ATF1-miR137 pathway. KEY POINTS: Calcium-Sensing Receptor (CaSR) activating mutations are the main cause of autosomal dominant hypocalcaemia (ADH) characterized by inappropriate renal calcium excretion leading to hypocalcaemia and hypercalciuria. Current treatments of ADH patients with parathyroid hormone, although improving hypocalcaemia, do not improve hypercalciuria or nephrocalcinosis. In vivo treatment with calcilytic JTT-305/MK-5442 ameliorates most of the ADH phenotypes of the CaSR knock-in mice including hypercalciuria or nephrocalcinosis and reverses the downregulation of the vasopressin-sensitive aquaporin-2 (AQP2) expression, providing direct evidence for a critical role of CaSR in impairing vasopressin response. The beneficial effect of calcilytic in reducing the risk of renal calcification may occur in a parathyroid hormone-independent action through vasopressin-dependent inhibition of cAMP synthesis in the thick ascending limb and in the collecting duct. The amelioration of most of the abnormalities in calcium metabolism including hypercalciuria, renal calcification, and AQP2-mediated osmotic water reabsorption makes calcilytic a good candidate as a novel therapeutic agent for ADH.
Patients receive placebo PO QD on days 1-28. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout the study.
Women's HARP is a multi-center, observational study which enrolls women with MI who are referred for cardiac catheterization. During the MI hospitalization, questionnaires will be administered to assess psychosocial stress leading up to the event (MI). Participants will also have the option to enroll in the HARP-Stress Ancillary Study and HARP-Platelet Sub-Study. Two months following MI, participants may be screened for the Stress Ancillary Study. Women with elevated perceived stress at screening will be enrolled. Patients will complete baseline assessments (self-report questionnaires and 7 days of wrist actigraphy) and then will be randomized to group-based stress management or to enhanced usual care (EUC). Both study arms involve 8 weekly phone sessions delivered by trained facilitators. Following intervention, participants in both study arms will repeat self-report questionnaires and 7 days of wrist actigraphy. Anticipate enrollment of approximately 200 women to meet target of 144 qualified women.
SAAP-148, a derivative of LL-37, exhibits a well-defined amphipathic structure and enhanced antimicrobial activity; however, it also displays significant cytotoxicity towards human cells. In this study, we employed Lys-scan to produce a series of amphiphilic SAAP-148 analogs derived from the SAAP-148 sequence to investigate the impact of the distribution of positively charged residues on the biological viability of the antimicrobial peptides (AMPs). The physical properties and biological activity of the designed peptides were subsequently compared. The substitution of lysine resulted in an increase in the overall charge of SAAP-148 and a decrease in its overall hydrophobicity and hyd. moment, except for SAAP-10 where an analogue substitution occurred at the 18th residue. The replacement of lysine led to a reduction in hemolytic activity compared to SAAP-148, with slightly higher haemolysis rates observed in SAAP-11 and SAAP-13. The cytotoxicity of peptides towards human normal lung epithelial cells (BEAS-2B) was closely linked to their haemolytic activity, indicating that substituting lysine may mitigate the cytotoxic effects of SAAP-148. Additionally, the arrangement of positively charged residues in the peptides significantly influenced its antimicrobial activity. Our findings suggest that the positioning of a positively charged residue has a significant impact on the biophysical properties of the peptide. Additionally, the substitution of lysine at different positions demonstrates an influence on the anti-lipopolysaccharide (anti-LPS) activity of SAAP-148. These discoveries provide valuable insights for the design and optimization of antimicrobial peptides, which will be advantageous for the future development of antimicrobial agents.
We propose to subcutaneously administer 0.5 MU/m2 of IL-2 daily to WAS subjects for 5 days. Research treatment will be repeated 2 and 4 months later. Inter-patient dose escalation will be employed to 1 MU/m2 and/or 2 MU/m2 based on safety as the primary endpoint.
The lipid metabolism adaptations of estrogen and progesterone receptor-positive breast cancer tumors from a mouse syngeneic model are investigated in relation to differences across the transition from hormone-dependent (HD) to hormone-independent (HI) tumor growth and the acquisition of endocrine therapy (ET) resistance (HIR tumors). Results are articulated with reported polar metabolome results to complete a metabolic picture of the above transitions and suggest markers of tumor progression and aggressiveness. Untargeted nuclear magnetic resonance metabolomics was used to analyze tumor and mammary tissue lipid extracts. Tumor progression (HD-HI-HIR) was accompanied by increased nonesterified cholesterol forms and phospholipids (phosphatidylcholine, phosphatidylethanolamine, sphingomyelins, and plasmalogens) and decreased relative contents of triglycerides and fatty acids. Predominating fatty acids became shorter and more saturated on average. These results were consistent with gradually more activated cholesterol synthesis, β-oxidation, and phospholipid biosynthesis to sustain tumor growth, as well as an increase in cholesterol (possibly oxysterol) forms. Particular compound levels and ratios were identified as potential endocrine tumor HD-HI-HIR progression markers, supporting new hypotheses to explain acquired ET resistance.
Session 2 for participants randomized to group MV will focus on learning strategies to live life according to their values. They will first engage in a reflection exercise to help identify their values, and then complete a worksheet. Couples will brain storm together strategies to ensure that their lives reflect their self-identified values. The instructor will go over the homework assignment. The interventionist will review the tools the couples had learned over the course of this program and help them proactively identify strategies to continue to implement them into their lives. Couples will receive instructions on how to continue with this program when no longer meeting with the interventionist.
The present invention relates to traditional Chinese medicine tablet preparation for treating coronary disease, and a preparation method and a device for the traditional Chinese medicine tablet preparation which is formed by combining valerian and red sage roots. The method heats and melts extracts of the valerian and the red sage roots with a water-soluble carrier. The mixture is then put into a dripping pill machine of the preparation device of the present invention. Medicine preparation is dripped into a die cavity to be cooled and molded, and the tablet preparation is formed. The tablet preparation of the present invention has portability, convenient administration and low production cost. Moreover, the solubility and a dissolution rate of the medicine are high. The present invention has the characteristics of rapid effect and high speed, and can meet the requirements of clinical treatment in the emergency of coronary disease.
This invention concerns binding domains e.g. single chain variable domains which are synthetic analogues of other single chain variable domains of members of an immunoglobulin family or superfamily. In the analogue, one or more amino acid residues is altered as compared to the other domain, so that the analogue is more hydrophilic than the natural domain. The altered amino acid is substituted with a residue which occurs in an analogous position in a member of an immunoglobulin family or superfamily. This increased hydrophilicity means that the synthetic analogue will show less non-specific binding than the natural domain. The analogue may retain the binding specificity of the natural domain. Alternatively, the complementarity determining regions may be altered to change the binding specificity. The invention also concerns methods for making these binding domains.
BACKGROUND: Neuroinflammation assumes a pivotal role in both the etiological underpinnings and the dynamic progression of sepsis-associated encephalopathy (SAE). The occurrence of cognitive deficits with SAE is associated with neuroinflammation. 4-phenyl butyrate (4-PBA) may control inflammation by inhibiting endoplasmic reticulum stress (ERS). The primary objective of this investigation is to scrutinize the effectiveness of 4-PBA in mitigating neuroinflammation induced by lipopolysaccharides (LPS) and its consequent impact on cognitive function decline.
METHODS: LPS-injected mice with SAE and LPS-treated BV2 cell were established to serve as experimental paradigms, both contributing to the investigative framework of the study. Cognitive functions were assessed by behavioral tests. Hippocampal neuronal damage was assessed using Golgi staining and Nissl staining. Quantitative PCR assay and immunofluorescence were used to analyze neuroinflammation. Mitochondrial function was examined using transmission electron microscopy. Protein expression analysis was conducted through the application of western blotting methodology, serving as the investigative approach to elucidate molecular signatures in the experimental framework. Endoplasmic reticulum and mitochondrial calcium flow were detected using flow cytometry. To delve deeper into the mechanistic intricacies, the administration of 4μ8c was employed to selectively impede the IRE1α/Xbp1s pathway, constituting a strategic intervention aimed at elucidating underlying regulatory processes.
RESULT: Expression levels of ERS-related proteins exhibited a significant upregulation in hippocampal tissues of LPS-treated mice when compared to wild-type (WT) counterparts. The administration of 4-PBA notably ameliorated memory deficits in LPS-treated mice. Furthermore, 4-PBA treatment was found to alleviate oxidative stress and neuroinflammation. Mechanistically, the IRE1α/Xbp1s-Ca2+ signaling pathway played a crucial role in mediating the beneficial effects of mitigating oxidative stress and maintaining mitochondrial calcium homeostasis, with inhibition of the IRE-related pathway displaying opposing effects.
CONCLUSION: Our results suggest that administration of 4-PBA treatment significantly attenuates ERS, alleviates cognitive decline, reduces inflammatory damage, and restores mitochondrial dynamics via the IRE1α/Xbp1s-Ca2+-associated pathway, which provides a new potential therapeutic approach to SAE.
BACKGROUND: Autoimmune diseases (ADs) are a category of conditions characterized by misrecognition of autologous tissues and organs by the immune system, leading to severe impairment of patients' health and quality of life. Increasing evidence suggests a connection between fluctuations in plasma metabolites and ADs. However, the existence of a causal relationship behind these associations remains uncertain.
METHODS: Applying the two-sample mendelian randomization (MR) method, the reciprocal causality between plasma metabolites and ADs was analyzed. We took the intersection of two metabolite genome-wide association study (GWAS) datasets for GWAS-meta and obtained 1,009 metabolites' GWAS data using METAL software. We accessed GWAS summary statistics for 5 common ADs, inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes (T1D), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) from published GWAS data. MR analyses were performed in discovery and replication stage simultaneously. Meanwhile, the reverse MR analysis was conducted to investigate the possibility of reverse causal association. Furthermore, a series of sensitivity analyses were conducted to validate the robustness of the results. These statistical analyses were conducted using R software. Finally, the web version of MetaboAnalyst 5.0. was applied to analyze metabolic pathways. Ultimately, we conducted ELISA assays on plasma samples from patients to validate the results.
RESULTS: 4 metabolites were identified to have causal relationships with IBD, 2 metabolites with MS, 13 metabolites with RA, and 4 metabolites with T1D. In the reverse MR analysis, we recognized causality between SLE and 22 metabolites, IBD and 4 metabolites, RA and 22 metabolites, and T1D and 37 metabolites. Additionally, 4 significant metabolic pathways were identified in RA by metabolic pathway analysis in the forward MR analysis. Correspondingly, in the reverse, 11 significant metabolic pathways in RA, 8 in SLE, and 4 in T1D were obtained using identical approaches. Furthermore, the protective role of glutamate was confirmed through ELISA assays.
CONCLUSIONS: Our research established a reciprocal causality between plasma metabolites and ADs. Furthermore, diverse metabolic pathways correlated with ADs were uncovered. Novel insights into the prediction and diagnosis were provided, as well as new targets for precise treatment of these conditions were discovered.
PURPOSE: A composition containing flavonoid for preventing alcoholic liver diseases is provided to reduce bitter taste of narirutin. CONSTITUTION: A flavonoid derivative is prepared by glycosylation or hydrolysis of flavonoid. The flavonoid includes hesperidin, hesperetin, naringin, naringenin, or narirutin. The glycolysation is induced by adding sugar substrate and glycosyltransferase CGT(cyclodextrin glucanotransferase). The sugar substrate is beta-cycliodextrin. A pharmaceutical and food compositions for preventing and treating alcoholic liver diseases contains glycosylated or hydrolyzed flavonoid derivatives.
Subjects will receive by oral inhalation FF 50 mcg once daily in the morning via ELLIPTA for 42 days. Subjects will continue to receive oral montelukast once daily in the evening and may use albuterol/salbutamol inhalation aerosol as needed.
Treatment-as-usual (TAU) will occur as any usual 12-week treatment. The therapists will be encouraged to discuss any of the presenting concerns reported by patients and supervision will include usual care.
Blood sampling collection: 12, 18 and 24 months after the vaccination. The study will enroll up to 30 healthy volunteers of both genders aged 18-55 inclusive who had been earlier immunized with medicinal product GamEvac-Combi in the dosages of 0.25 ml, during the study under Protocol 01-COMBI-2015 in October-November 2015.
In the induction chemotherapy phase, TP regimen (Docetaxel 75mg/m2, D1 + DDP 25mg/m2, D1-3, repeat every 3 weeks) or GP regimen (Gemcitabine 1.0g/m2, D1, 8 + DDP 25mg/m2 , D1-3, repeat every 3 weeks) will be used. Cetuximab 400mg/m2 will be used one week before radiotherapy and 250mg/m2/week during IMRT, or nimotuzumab 200mg/week; meanwhile, cisplatin 80mg/m2 will be used every 3 weeks.
Deep dyspareunia is one of the main symptoms of endometriosis. It appears to be submerged by a two-way disconnection between patients and their physicians. The aim of our review is to provide clear, ready-to-use advice on how to manage deep dyspareunia overcoming the gap in communication. Sexual history should always be taken as part of routine health care in these regards, using a patient-centered approach. An educational pelvic examination, which actively includes patients in the identification of painful areas, may prove useful to improve patients' understanding of their condition. Correlating painful pelvic areas with sexual positions and inviting patients to adopt alternative positions may represent a simple but extremely effective coping strategy to mitigate pain. Revealing and explaining to partners the nature of the pain is essential to allow them to take part in shared research of coping mechanisms, empowering the couple to make choices and changes. Couples who do not feel comfortable talking about intimacy by themselves may find that including a psychotherapist or a sexual therapist, may be a good way to start communication. Investigating and managing dyspareunia during medical encounters is a medical and ethical duty all healthcare practitioners should pursue.
The present invention provides a new method for preparing active components of erigeron. The present invention is characterized in that extraction is carried out with water containing soda at normal temperature, and refining is carried out with polyamide column adsorption. The method simply uses water and alcohol as solvent, and has the advantages of short process, stable component, low cost, simple operation and high yield. The obtained active components mainly contain phenol acid components of flavone and caffeoyl quinic acid without containing hepatotoxin components namely pyromeconic acid. The active components have the advantages of high efficiency and low toxin. The active components can be used for preparing various oral administration or injection dosage forms separately or in the mode that the active components are matched with other medicinally allowable materials, and are suitable for preventing and treating cardiovascular and cerebrovascular diseases.
PURPOSE: Tumors affecting the female genital tract and their treatments have the potential to induce adverse modifications in vaginal health and impact personal aspects of patient's lives. Vulvovaginal atrophy is one of the morphological changes observed in individuals with a history of gynecological cancer, influenced both by the biological environment of tumors and the main therapeutic modalities employed. Therefore, the purpose of this study was to identify approaches to treat vulvovaginal atrophy while assessing the impact on the emotional and sexual health of women diagnosed with gynecological cancers.
METHODS: To achieve this goal, a systematic review was conducted following the methodological guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The databases used for literature research were PubMed and Web of Science.
RESULTS: Initially, 886 articles were obtained. After eliminating duplicates and applying inclusion/exclusion criteria, seven articles were selected for analysis. The period of highest publication activity spanned from 2017 to 2020, with the majority conducted in Italy. Five treatment modalities were identified and categorized as vaginal suppository, oral medication, surgical procedure, CO2 laser therapy, and vaginal dilator. Twenty-four outcomes related to vaginal health and 30 outcomes related to overall, sexual, and emotional quality of life were analyzed.
CONCLUSION: In general, all interventions demonstrated the ability to improve vaginal health or, at the very least, the sexual health of patients. Thus, despite limitations, all treatments have the potential to address vulvovaginal atrophy in patients with a history of gynecological cancer.
Older livers are more prone to hepatic ischaemia/reperfusion injury (HIRI), which severely limits their utilization in liver transplantation. The potential mechanism remains unclear. Here, we demonstrate older livers exhibit increased ferroptosis during HIRI. Inhibiting ferroptosis significantly attenuates older HIRI phenotypes. Mass spectrometry reveals that fat mass and obesity-associated gene (FTO) expression is downregulated in older livers, especially during HIRI. Overexpressing FTO improves older HIRI phenotypes by inhibiting ferroptosis. Mechanistically, acyl-CoA synthetase long chain family 4 (ACSL4) and transferrin receptor protein 1 (TFRC), two key positive contributors to ferroptosis, are FTO targets. For ameliorative effect, FTO requires the inhibition of Acsl4 and Tfrc mRNA stability in a m6A-dependent manner. Furthermore, we demonstrate nicotinamide mononucleotide can upregulate FTO demethylase activity, suppressing ferroptosis and decreasing older HIRI. Collectively, these findings reveal an FTO-ACSL4/TFRC regulatory pathway that contributes to the pathogenesis of older HIRI, providing insight into the clinical translation of strategies related to the demethylase activity of FTO to improve graft function after older donor liver transplantation.