anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Inflammation plays a critical role in the development of numerous diseases. Cannabidiol (CBD), found in hemp, exhibits significant pharmacological activities. Accumulating evidence suggests that CBD has anti-inflammatory and cardiovascular protection effects, but the potential mechanisms require further exploration. In this study, we aimed to reveal the mechanisms of CBD against high-fat, high-cholesterol (HFC) diet-induced inflammation combining metabolomics with network pharmacology. First, plasma lipidomics results indicated that oxidized lipids could serve as potential biomarkers for HFC diet-induced inflammation, and CBD reversed the elevated levels of oxidized lipids. The HFC diet was also found to enhance intestinal permeability, facilitating the entry of lipopolysaccharides (LPSs) into the circulatory system and subsequently increasing systemic inflammation. Additionally, cell metabolomic results indicated that CBD could reverse 10 important differential metabolites in LPS-induced RAW 264.7 cells. Using network pharmacology, we identified 49 core targets, and enrichment analysis revealed that arachidonic acid was the most significantly affected by CBD, which was closely associated with inflammation. Further integrated analysis focused on three key targets, including PTGS2, ALOX5, and ALOX15. Molecular docking showed high affinities between key targets and CBD, and qPCR further demonstrated that CBD could reverse the mRNA expression of these key targets in RAW 264.7 cells. Collectively, this finding integrates lipidomics and metabolomics with network pharmacology to elucidate the anti-inflammatory effects of CBD and validates key therapeutic targets.
Disease risk alleles influence the composition of cells present in the body, but modeling genetic effects on the cell states revealed by single-cell profiling is difficult because variant-associated states may reflect diverse combinations of the profiled cell features that are challenging to predefine. We introduce Genotype-Neighborhood Associations (GeNA), a statistical tool to identify cell-state abundance quantitative trait loci (csaQTLs) in high-dimensional single-cell datasets. Instead of testing associations to predefined cell states, GeNA flexibly identifies the cell states whose abundance is most associated with genetic variants. In a genome-wide survey of single-cell RNA sequencing peripheral blood profiling from 969 individuals, GeNA identifies five independent loci associated with shifts in the relative abundance of immune cell states. For example, rs3003-T (P = 1.96 × 10-11) associates with increased abundance of natural killer cells expressing tumor necrosis factor response programs. This csaQTL colocalizes with increased risk for psoriasis, an autoimmune disease that responds to anti-tumor necrosis factor treatments. Flexibly characterizing csaQTLs for granular cell states may help illuminate how genetic background alters cellular composition to confer disease risk.
Our ACT intervention will include 6 weekly 1-hour telephone sessions and 1 booster session offered 1 month after session 6 designed to increase psychological flexibility through practice of one or more of the six skills in each session. Although these are ideally spaced 1 week apart, participants will have up to 12 weeks to complete the 6 sessions. Each session will include guided mindfulness practice that encourages non-judgmental awareness of the present moment to increase psychological flexibility; brief (10-minute) study-provided audio recordings will enable participants to practice mindfulness at home. Caregivers will also identify deeply-held values to serve as a guide when choosing how to spend limited time or energy and will set values-based action goals each week. A booster session will be provided one month after session 6 to reinforce skills learned.
Two subjects in Part A will receive starting dose level of GSK2398852 as 5 milligram (mg) \[approximately equivalent to 0.1 mg/kilogram (kg)\]. The next escalation dose levels in two subjects each are proposed as 1 mg/kg, 3 mg/kg, 10 mg/kg and 30 mg/kg. GSK2315698 will be administered at variable dosed until the concentration of the SAP mAb has fallen below 100 ng/mL.
AIM: Tirzepatide (Tzp), a novel dual agonist glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1, is approved for treating insulin resistance and obesity, and menopausal women consuming a high-calorie diet are a target to study the Tzp effect. Therefore, we aimed to allometrically scale body weight (BW) in Tzp-treated obese diabetic menopausal mice.
MATERIALS AND METHODS: Three-month-old C57BL/6 female mice had bilateral ovariectomy (Ovx) or a sham procedure and for 12 weeks were fed a control diet or a high-fat and high sucrose diet (n = 120/each group [control (C), obese diabetic (Od), Ovx (O), sham (S), Tzp (T)]). Tzp was subcutaneously administered (10 nmol/kg) or vehicle once a day for an additional 4 weeks. The analysis considered log-transformed data and the allometric equation log y = log a + b log x.
RESULTS: Od and OdO showed more upward slopes than C and CO. In C, BW was non-allometric by T administration. Od and OdO showed slightly positive slopes (more prominent in OdO than Od). OdT and OdOT showed negative slopes, significant intercepts, and more robust Pearson coefficients than untreated ones. A potent drug effect was seen with BW allometric decline. Interactions between diet versus Ovx and diet versus Tzp affected weight gain. Diet versus Ovx versus Tzp affected food intake.
CONCLUSIONS: A model was developed to show three usual factors observed in mature women. Notably, Tzp improved the metabolism and weight loss of OdO mice. Tzp-treated mice showed negative allometric BW across treatment time, which is a quantitative assessment that allows better comparison between results.
The present invention relates to a preparation technology and a production method for an integrated new formulation of a radix bupleuri decoction minus pinellia ternate plus snakegourd root, wherein the raw materials of active ingredients comprise: 24 parts by weight ofradix bupleuri, 9 parts by weight of genseng, 9 parts by weight of radix scutellariae, 9 parts by weight of licorice, 12 parts by weight of snakegourd root, 6 parts by weight of dried ginger, and 12 parts by weight of jujube. The production process of the integrated new formulation comprises the following steps of: supersonic air-jet crushing, alcohol-water extraction, ultrasonic crushing extraction, water decocting concentration, supersonic spray drying, nanometer grinding, high pressure homogenization, nano particle preparation and the like. According to the invention, the advantages, such as multi-synergism, multi-target, embodied by a nano-carrier coupling technique, are focused to be taken of. After the integrated new formulation of radix bupleuri decoction minus pinellia ternate plus snakegourd root is subjected to scale production, the production cost can be greatly reduced, the quality of products is greatly improved and the targeting property and the sustained and controlled release performance of the medicament are enhanced. The internal and external administration of the integrated new formulation of radix bupleuri decoction minus pinellia ternate plus snakegourd root can be realized simultaneously, and can be respectively taken in four time slices according to midnight-noon ebb-flow and qi and blood flowing rule of a human body. The integrated new formulation of radix bupleuri decoction minus pinellia ternate plus snakegourd root can be further prepared into films and transdermal agents which are respectively stuck to different parts of a human body according to the midnight-noon ebb-flow and qi and blood flowing rule of the human body and can be directly absorbed through skin.
INCA32459 will be administered at a protocol defined starting regimen intravenously. Subsequent dose regimens will be determined during study conduct.
Receives paracoracoid subscapularis plane block with the ultrasound. Using a 50mm 22G block needle 15ml of 0.5% Ropivacaine will be deposited anterior to the fascia of subscapularis muscle after eliciting a motor response with 0.6mA current delivered through the needle. Following this, superficial cervical plexus block will be done using 3mL of 0.5% ropivacaine similar to group 1.
Participants will receive cervical cancer prevention education, and provide self-administered vaginal or cervical specimens and provide specimens of plants, plant-products or herbs most commonly used in the intravaginal cleansing practice of twalet deba. Total expected participation is about 30 days.
FIELD: medicine. ^ SUBSTANCE: invention relates to medicine, in particular to otolaryngology, and can be used for treatment of exudative otitis media. Method includes shunting of tympanic cavity with hollow prosthesis, introduction to patients in post-operation period of antibacterial medication of wide spectrum of action, mucolytic medication, endaural introduction of proteolytic medication, vasoconstrictive drops into nose. Additionally simultaneously, perorally introduced is preparation "Reaferon-EC-Lipint" in dose: children of 3-15 years 125000 IU daily 2 times per day for 7 days, children from 16-18 years - 250000 IU daily 2 times per day for 7 days. From eighth to tenth day of treatment patients continue to obtain peroral introduction of Reaferon-EC-Lipint in the following dose: children of 3-15 years 250000 IU daily 2 times per day for 3 days, children from 16-18 years -500000 IU daily 2 times per day for 3 days. ^ EFFECT: method makes it possible to increase efficiency of treatment of exudative otitis media in children and reduce number of disease recurrences. ^ 1 tbl, 2 ex
Excessive extracellular matrix deposition and increased intrahepatic angiogenesis are prominent features of cirrhosis. β-arrestin2 is thought to be involved in the pathological processes of various fibrotic diseases. This study aimed to investigate the role and possible mechanism of β-arrestin2 in the angiogenesis of cirrhosis. Firstly, β-arrestin2 expression in liver tissues of cirrhotic patients was detected, and the correlation between β-arrestin2 and α-SMA, CD-31, PDGF, and VEGF indexes was analyzed. Then, after liver cirrhosis induced by CCL4 in Arrb2-KO mice (β-arrestin2 coding gene), liver histopathological changes were observed, and the expressions of α-SMA, CD-31, PDGF, VEGF, and VEGFR2 were detected. Finally, VEGF-A was used to treat human liver sinusoidal endothelial cells (LSECs) to simulate pathological conditions. After transfection with si-ARRB2, the cell activity, MDA and GSH-PX activities, cell invasion, angiogenesis, and the expressions of α-SMA, CD-31, and VEGF/VEGFR2 pathway were detected. Results showed that β-arrestin2 expression in the liver increased significantly during cirrhosis and was positively correlated with angiogenesis. In vivo, Arrb2-KO significantly inhibited fibrosis and angiogenesis in cirrhotic mice, and decreased the expressions of α-SMA, CD31, PDGF, VEGF, and VEGFR2. Studies using LSECs in vitro showed that after intervention of ARRB2, the activity of LSECs and the number of invasions and tubule formations were significantly reduced. Similarly, after transfection with si-ARRB2, the expressions of α-SMA, CD31, PDGF, VEGF, and VEGFR2 in LSECs were significantly decreased. Collectively, β-arrestin2 aggravated cirrhosis by promoting the angiogenesis of LSECs. Blocking β-arrestin2 may be an important target against angiogenesis and fibrosis in cirrhosis.
Stroke is the second most important cause of mortality and morbidity in the world. Currently, the standard treatment for ischemic stroke is an intravenous tissue plasminogen activator(tPA; alteplase) and/or endovascular thrombectomy. However, the therapeutic time window for these treatments is narrow. Besides, endovascular thrombectomy requires specialized stroke expertise and endovascular skills. Less than 5% of ischemic stroke patients are treated by these therapy and not all patients achieve good outcomes. There is still a lack of therapy for the reduction disability from stroke. In 2018, at least 40 clinical trials intent to treat ischemic stroke using cell therapy. In particular, MSCs have shown great potential in the reduction disability from acute ischemic stroke (AIS). Meridigen is developing UMC119-06, a mesenchymal stem cell derived from human umbilical cord for the treatment of AIS disease.
FIELD: medicine. SUBSTANCE: method involves administering phonophoresis treatment with copper biological complex applied to lesion foci. Biologically active points are additionally stimulated with electromagnetic radiation of extremely high frequency. Power density does not exceed 10- mW/cm 2 . Autonomous electrostimulation of gastroenteric tract is prescribed to continue the treatment after giving 5-6 sessions. EFFECT: accelerated treatment course.
The lungs represent the most common site of metastasis for osteosarcoma (OS). Despite our advances in developing targeted therapies for treating solid malignancies, broad acting chemotherapies remain the first line treatment for OS. In assaying the efficacy of approved therapeutics for non-OS malignancies, we previously identified the histone deacetylase 1 and 2 (HDAC1 and 2) inhibitor, romidepsin, as effective for the treatment of established lung metastatic OS. Yet, romidepsin has noted toxicities in humans and so here we aimed to define the primary mechanisms through which HDAC1/2 mediate OS progression to identify more selective druggable targets/pathways. Microarray and proteomics analyses of romidepsin treated OS cells revealed a significant suppression of neuropilin-1 (NRP1), a known regulator of cancer cell migration and invasion. Silencing of NRP1 significantly reduced OS proliferation, migration, invasion and adhesion in vitro. More strikingly, in vivo, reduced NRP1 expression significantly mitigated the lung metastatic potential of OS in two independent models (K7M2 and SAOS-LM7). Mechanistically, our data point to NRP1 mediating this effect via the down regulation of migration machinery, namely SRC, FAK and ROCK1 expression/activity, that is in part, related to NRP1 interaction with integrin beta 1 (ITGB1). In summary, our data indicate that romidepsin down regulation of NRP1 significantly mitigates the ability of OS cells to seed the lung and establish metastases, and that targeting NRP1 or its effectors with selective inhibitors may be a viable means with which to prevent this deadly aspect of the disease.
Only liquid diet and polyethylene glycol with 2L water was administrated orally 1 day before surgery. Enteroclysis was conduted for patients on surgical morning.
BACKGROUND: Endothelial activation promotes the release of procoagulant extracellular vesicles and inflammatory mediators from specialized storage granules. Endothelial membrane exocytosis is controlled by phosphorylation. We hypothesized that the absence of PTP1B (protein tyrosine phosphatase 1B) in endothelial cells promotes venous thromboinflammation by triggering endothelial membrane fusion and exocytosis.
METHODS: Mice with inducible endothelial deletion of PTP1B (End.PTP1B-KO) underwent inferior vena cava ligation to induce stenosis and venous thrombosis. Primary endothelial cells from transgenic mice and human umbilical vein endothelial cells were used for mechanistic studies.
RESULTS: Vascular ultrasound and histology showed significantly larger venous thrombi containing higher numbers of Ly6G (lymphocyte antigen 6 family member G)-positive neutrophils in mice with endothelial PTP1B deletion, and intravital microscopy confirmed the more pronounced neutrophil recruitment following inferior vena cava ligation. RT2 PCR profiler array and immunocytochemistry analysis revealed increased endothelial activation and adhesion molecule expression in primary End.PTP1B-KO endothelial cells, including CD62P (P-selectin) and VWF (von Willebrand factor). Pretreatment with the NF-κB (nuclear factor kappa B) kinase inhibitor BAY11-7082, antibodies neutralizing CD162 (P-selectin glycoprotein ligand-1) or VWF, or arginylglycylaspartic acid integrin-blocking peptides abolished the neutrophil adhesion to End.PTP1B-KO endothelial cells in vitro. Circulating levels of annexin V+ procoagulant endothelial CD62E+ (E-selectin) and neutrophil (Ly6G+) extracellular vesicles were also elevated in End.PTP1B-KO mice after inferior vena cava ligation. Higher plasma MPO (myeloperoxidase) and Cit-H3 (citrullinated histone-3) levels and neutrophil elastase activity indicated neutrophil activation and extracellular trap formation. Infusion of End.PTP1B-KO extracellular vesicles into C57BL/6J wild-type mice most prominently enhanced the recruitment of endogenous neutrophils, and this response was blunted in VWF-deficient mice or by VWF-blocking antibodies. Reduced PTP1B binding and tyrosine dephosphorylation of SNAP23 (synaptosome-associated protein 23) resulting in increased VWF exocytosis and neutrophil adhesion were identified as mechanisms, all of which could be restored by NF-κB kinase inhibition using BAY11-7082.
CONCLUSIONS: Our findings show that endothelial PTP1B deletion promotes venous thromboinflammation by enhancing SNAP23 phosphorylation, endothelial VWF exocytosis, and neutrophil recruitment.
The present invention describes oligosaccharide sequences, which are specifically expressed by human tumors. The present invention is related to a method of determining an oligosaccharide sequence, which comprises a tumor specific terminal N-acetylglucosamine residue, in a biological sample, the presence of said sequence in said sample being an indication of the presence of cancer. The present invention provides antigenic substances comprising said oligosaccharide sequences in a polyvalent form and it further provides diagnostic agents, pharmaceutical compositions and cancer vaccines comprising said oligosaccharide sequences or substances binding to said oligosaccharide sequences. The present invention is also related to methods for the treatment of cancer. Further the present invention relates to a method of treatment or diagnosis of cancer by transferring a modified monosaccharide to cancer cells by glycosyl transferase. It also concerns an enzyme substrate composition capable of being transferred to a surface of pathogenic entity for use as medecine.
PROBLEM TO BE SOLVED: To obtain whole amino acids constituting proteins useful for a food, a feed, etc., from an organic industrial waste material, etc., and not requiring a purification of the reaction products by performing a hydrolysis of the proteins with a supercritical state or a sub-supercritical state water. SOLUTION: This method for producing amino acids or peptides by using a supercritical water is to perform a hydrolysis of proteins, preferably edible proteins, especially proteins derived from a corn by using a supercritical state or a sub-supercritical state water under conditions at 300-400 deg.C temperature, under 221-1000-atm pressure, and 1-40sec reaction time. Further, it is preferable to obtain peptides under a hydrolysis condition at 350-400 deg.C temperature, 221-1000-atm pressure and 4-30min reaction time, and e.g. 10-50 pt.wt. water is preferably used based on 1 pts.wt. protein.
PROBLEM TO BE SOLVED: To prepare an antiaging agent, comprising one or more extracts from specific plants blended as active ingredients, having promoting actions, etc., on the production of hyaluronic acid and capable of retaining the tensity or elasticity of skin and maintaining a state of youthful skin. SOLUTION: This antiaging agent is prepared by blending one or more selected from extracts obtained from plants comprising Kayu legi (botanical name: Glycyrrhiza glabra), Kelabet (botanical name: Trigonella foenum-graecum), Lempuyang (botanical name: Zingiber aromaticum Mal.) and Remujung (botanical name: Orthosiphon aristatus) therein. All the plants grow in a dry grassland, a pasture, etc., of Indonesia. The amount of the blended extracts is 0.0005-20.0wt.%, preferably 0.001-10.0wt.% expressed in terms of a dry substance in the total amount of a preparation for external use. The antiaging agent can suitably be used for a makeup cosmetic, a cosmetic for hair of the head, a bathing agent, etc., including a basic cosmetic.
Recent data from the French perinatal cohort and others indicate that HIV-RNA levels at delivery correlate with risk of transmission among women treated with antiretroviral agents. Most of these treatments include zidovudine alone or in combination. Mitochondrial toxicity related to nucleoside analogues exposure (zidovudine and lamivudine) has been reported in adults and in infants with in utero exposure to these drugs. In addition, biological markers of genotoxicity on nuclear DNA have recently been shown in exposed newborn. These issues raised the concern of the risk/benefit of multiple therapy in the context of mother to child transmission for women who do not meet the standard criteria for antiretroviral therapy. In women with CD4≥350 and VL\<30 000 copies/ml a treatment with lopinavir/ritonavir should achieve a rapid control of HIV1 viremia below 1000 copies/ml without harm in term of resistance. In this study we would like to assess under strict control, the safety and efficacy of such regimen compared to the same boosted PI + zidovudine and lamivudine as standard regimen. The treatment will start at 26 weeks of gestation, and the follow up will include safety and efficacy parameters as well as pharmacokinetics in plasma and genital tract for the women, blood/cord ratio, testing for ARV resistance. Women will stop their treatment after delivery. Infants will be closely monitored up to 24 months with HIV DNA and HIV.RNA-PCR for HIV testing and biochemical and haematology usual safety evaluation. In addition frozen samples will be collected for specific evaluation of nucleoside analogue foetal mitochondrial and nuclear DNA interactions.

In term of transmission safety, the end point would be to reach a viral load below 200 copies after 8 weeks of treatment. In case of failure, this would allow a sufficient delay for a treatment modification: i.e. addition of NRTI and an elective caesarian could be programmed.