anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Cardiovascular diseases (CVDs), a group of disorders affecting the heart or blood vessels, are the primary cause of death worldwide, with an immense impact on patient quality of life and disability. According to the World Health Organization, CVD takes an estimated 17.9 million lives each year, where more than four out of five CVD deaths are due to heart attacks and strokes. In the decades to come, an increased prevalence of age-related CVD, such as atherosclerosis, coronary artery stenosis, myocardial infarction (MI), valvular heart disease, and heart failure (HF) will contribute to an even greater health and economic burden as the global average life expectancy increases and consequently the world's population continues to age. Considering this, it is important to focus our research efforts on understanding the fundamental mechanisms underlying CVD. In this review, we focus on cellular senescence and mitochondrial dysfunction, which have long been established to contribute to CVD. We also assess the recent advances in targeting mitochondrial dysfunction including energy starvation and oxidative stress, mitochondria dynamics imbalance, cell apoptosis, mitophagy, and senescence with a focus on therapies that influence both and therefore perhaps represent strategies with the most clinical potential, range, and utility.
This is a double-blind, placebo controlled, parallel-group, dose finding study. Eligible subjects will be randomized to receive one of two doses of RGN-352 or matching placebo with an equal allocation ratio (i.e., 1:1:1). Approximately 75 subjects will be randomized to study treatment to achieve at least 60 evaluable subjects with 20 to 25 subjects per group. Subjects will be randomized to receive one of two RGN-352 doses of 1200 mg, or 450 mg, or placebo, administered iv by iv push daily for the first 3 consecutive days and weekly for 4 consecutive weeks. Study subjects will undergo cardiac angiography to assess initial coronary artery patency and Thrombolysis In Myocardial Infarction flow grade both pre- and post-percutaneous coronary intervention (PCI) angioplasty. A total of 7 doses will be administrated over the treatment period. The first dose of either RGN-352 or placebo will be administered to randomized subjects following PCI angioplasty and specifically within 30 minutes after balloon deflation, with a further 2 doses. The remaining 4 doses will be given weekly for 4 consecutive weeks. Follow-up is on Months 2, 4, and 6.
This invention discloses purifying method of human glutathione-S-transfering enzyme pi. The procedures are showed as following process (1) E.coli BL21/DE3 strain contains expression vector pET-28a/hGSTpi is inoculated in LB solid culture medium, then it is surged and cultured, and the thalli is centrifugally collected. (2) The thalli precipitation is collected by adding combining buffer solution with pH7.9 into every one gram precipitation, supernatant is picked after supersonic crashing and centrifuging, and then it is eluted by buffer solution. (3) The elution upper heat removing is imidazole removed by dialysate 1, and then dialysate 2 is used to determine enzyme activity. (4) PBS buffer solution is used to dialysis, His6 mark is hydrolyzed cut by thrombin to get human glutathione-S-transfering enzyme hGSTpi. The recombination albumen purity in the hGSTpi is high in this invention, and inactive dimmer formed by atmospheric oxidation is little. Inflammation can be effectively controlled by hGSTpi's application in inflammation curing, and its affect to economy immune system is little, and side effect is also little.
Nocebo effects in pain (nocebo hyperalgesia) have been thoroughly researched, and negative expectancies have been proposed as a key factor in causing nocebo hyperalgesia. However, little is known about the psychological mechanisms by which expectations exacerbate the perception of pain. A potential mechanism that has been proposed within wider pain research is pain-related attention. The aim of the present study was thus to explore whether attention bias (AB) to pain influenced nocebo hyperalgesia. One-hundred and thirty-four healthy participants were randomized in a 2 (AB training: towards vs away from pain) × 2 (nocebo condition: nocebo vs control) design. Pain-related AB was manipulated through a novel, partially gaze-contingent dot-probe task. Participants then completed either a nocebo instruction and conditioning paradigm or a matched control condition. Primary outcomes were measures of expectancy, anticipatory anxiety, and pain intensity completed during a nocebo test phase. Results showed that the AB manipulation was unsuccessful in inducing ABs either toward or away from pain. The nocebo paradigm induced significantly greater expectancy, anticipatory anxiety, and pain intensity for the nocebo groups compared to the control groups. In a posthoc analysis of participants with correctly induced ABs, AB towards pain amplified nocebo hyperalgesia, expectancy, and anticipatory anxiety relative to AB away from pain. The results are consistent with the expectancy model of nocebo effects and additionally identify anticipatory anxiety as an additional factor. Regarding AB, research is needed to develop reliable means to change attention sample-wide to corroborate the present findings. PERSPECTIVE: This article explores the role of AB, expectancy, and anticipatory anxiety in nocebo hyperalgesia. The study shows that expectancy can trigger anticipatory anxiety that exacerbates nocebo hyperalgesia. Further, successful AB training towards pain heightens nocebo hyperalgesia. These findings identify candidate psychological factors to target in minimizing nocebo hyperalgesia.
Doxorubicin (Dox), an anthracycline antibiotic, is widely used in cancer treatment. Although its antitumor efficacy appears significant, its clinical use is greatly restricted by its induction of cardiotoxicity. Cardiac senescence drives the Dox-induced cardiotoxicity, but whether diminishing these senescent cardiomyocytes could alleviate the cardiotoxicity remains unclear. Here, we assessed whether senescent cardiomyocytes have a senescence-associated secretory phenotype (SASP) that affects healthy non-senescent cardiomyocytes, rendering them senescent via the delivery of exosomes. Additionally, we explored whether targeting SASP senescent cardiomyocytes using a Bcl-2 inhibitor could alleviate cardiotoxicity. Cardiac damage was induced in a mouse model of continuous Dox treatment in vivo, and cardiomyocytes in vitro. Immunofluorescence of the senescence markers of Cdkn2a, Cdkn1a and γ-H2A.X was used to assess the SASP in the Dox-treated heart. To explore the molecular mechanisms involved, the Bcl-2 inhibitor ABT-199 was employed to eliminate SASP senescent cardiomyocytes. We show that the cardiomyocytes acquire a SASP during Dox treatment. The senescent cardiomyocytes upregulated Bcl-2, although treatment of mice with ABT-199 selectively eliminated SASP senescent cardiomyocytes involved in Dox-induced cardiotoxicity, thus leading to partial alleviation of Dox-induced cardiotoxicity. Moreover, we concluded that SASP factors secreted by senescent cardiomyocytes induced by Dox renders otherwise healthy cardiomyocytes senescent through exosome delivery. Our findings suggest that SASP senescent cardiomyocytes are a significant component of the pathogenesis of Dox-dependent cardiotoxicity and indicate that targeting the clearance of SASP senescent cardiomyocytes could be a new therapeutic approach for Dox-induced cardiac injury.
PROBLEM TO BE SOLVED: To synthesize the subject compound having phenyl group at the 2-position and useful as an intermediate for physiologically active substances such as medicines or agrochemicals by condensing two molecules of a phenol in the presence of a Grignard reagent according to the Diels-Alder reaction. SOLUTION: Two molecules of a phenol represented by formula I (R1, R3 and R5 are each H or a 1-9C alkyl; R2 and R4 are each H, a 1-9C alkyl or a protecting group of hydroxyl group) are condensed in the presence of a Grignard reagent according to the Diels-Alder reaction to thereby produce the objective compound represented by formula II or III. The above reaction is carried out in an aromatic solvent such as benzene, toluene or xylene at 60-80 deg.C by using the Grignard reagent (e.g. ethylmagnesium bromide) in an equivalent amount of preferably 0.5-2.0 based on a substrate. The compound represented by formula I is prepared by reducing the carbonyl of a compound obtained by condensing, e.g. a compound represented by formula IV with a carboxylic acid in the presence of a Lewis acid.
The invention provides a cholla stem and aloes anticancer capsule and the preparation method thereof. Added with alcohol, the Cholla stem is reflux extracted in 80 DEG C water bath. After being dried, the dregs of the decoction are extracted for three times by being boiled in 85 DEG C water. Extracts are concentrated to a thick state with the pressure goes down, and then is added with alcohol making the final concentration of the alcohol between 75 to 80 percent, and is kept still for 48 hours, then suction filtration is performed. The deposition is pumping washed by dehydrated alcohol, and solvent is volatilized until dry. After the beating of fresh aloes, added with alcohol, the serosity is reflux extracted in water bath of a constant temperature of 80 DEG C. After extraction and filtration, the gruffs is dried, added with 3 times amount of distilled water, and is extracted in 90 DEG C water bath for 60 minutes, and then is filtrated. After queous extraction according to the conditions for three times, the gruffs is add with dehydrated alcohol, making the final concentration 80 percent, and is kept still for 48 hours, and then is filtrated. The precipitation is pumping washed by dehydrated alcohol, and then is volatilized until dry. The aqueous extracts of cholla stem and aloes are mixed according to the proportion by weight of 1:1 and are packed into capsules. The production obtained from the method of the invention not only has immunologic enhancement but also cytotoxicity.
The present invention provides a combination of IL-12 and IFN alpha  together with a pharmaceutically acceptable carrier useful for treatment and prophylaxis of infectious diseases, preferably chronic infectious diseases and more preferably viral infections, e.g. HSV, HIV, Hepatitis B, Hepatitis C, papilloma etc., bacterial infections, e.g. tuberculosis, salmonellosis, listeriosis, etc., and parasite infections, e.g. malaria, leishmaniasis, and schistosomiasis. These compositions are characterized by the synergistic interaction of IL-12 and IFN alpha . The present invention also provides the use of the above combination for the treatment and prophylaxis of infectious diseases.
The present invention provides a non parenteral and non ocular herbal synergistic detoxifier composition effective for blood purification, blood detoxification and in the treatment and management of disorders related to accumulation of toxins in the body. The present invention also provided a method of preparation of this formulation. In a preferred embodiment, the composition comprises Echinacea purpurea leaves, Andrographis paniculata leaves, Boerhaavia diffusa whole plant, Arctium lappa root, Rubia cordifolia root; effective amount of one or more bio - availability enhancer. The bio - availability enhancer may be of herbal origin or chemical origin. The bio - availability enhancer of herbal origin may selected from the group includingextract or powder of Berberis aristata stem and Tinospora cordifolia stem. The bio - availability enhancer of chemical origin may be selected from the group including gluceryl mono oleate, poly vinyl alcohol, Span 80, Tween 80, Tween 20 and PEG 200 to PEG 6000 or a combination thereof. The composition may further contain Pothos aureus, leaves of Ixora coccinea, stems of Jacaranda mimosifolia, roots of Hemidesmus indicus, heartwood of Acacia catechu, stem of Cassia biflorain, leaf of Cassia seamia and flower of Dahlia pinnata.
This group has routine CIC education. They fill the scales before discharge and 12. week after discharge.
FIELD: organic chemistry. SUBSTANCE: derivatives of 5-membered heteroaryloxazolidinone of the general formula (I): $$$ where: $$$ and A have values given in invention description as a mixture of isomers or separate isomers, their salt and S-oxides. Invention relates to also pharmaceutical composition containing at least one pharmaceutically acceptable carrier and one active component. Composition has at least one derivative of 5-membered heteroaryloxazolidinone of the indicated above general formula (I) $$$ as a mixture of isomers or separate isomer, its salt and S-oxide as an active component taken at effective dose. Synthesized derivatives show antibacterial activity. EFFECT: improved method of synthesis.
Glenohumeral biomechanics after rotator cuff (RC) tears have not been fully elucidated. This study aimed to investigate the muscle compensatory mechanism in weight-bearing shoulders with RC tears and asses the induced pathomechanics (i.e., glenohumeral translation, joint instability, center of force (CoF), joint reaction force). An experimental, glenohumeral simulator with muscle-mimicking cable system was used to simulate 30° scaption motion. Eight fresh-frozen shoulders were prepared and mounted in the simulator. Specimen-specific scapular anthropometry was used to test six RC tear types, with intact RC serving as the control, and three weight-bearing loads, with the non-weight-bearing condition serving as the control. Glenohumeral translation was calculated using instantaneous helical axis. CoF, muscle forces, and joint reaction forces were measured using force sensors integrated into the simulator. Linear mixed effects models (RC tear type and weight-bearing) with random effects (specimen and sex) were used to assess differences in glenohumeral biomechanics. RC tears did not change the glenohumeral translation (p > 0.05) but shifted the CoF superiorly (p ≤ 0.005). Glenohumeral translation and joint reaction forces increased with increasing weight bearing (p < 0.001). RC and deltoid muscle forces increased with the presence of RC tears (p ≤ 0.046) and increased weight bearing (p ≤ 0.042). The synergistic muscles compensated for the torn RC tendons, and the glenohumeral translation remained comparable to that for the intact RC tendons. However, in RC tears, the more superior CoF was close to where glenoid erosion occurs in RC tear patients with secondary osteoarthritis. These findings underscore the importance of early detection and precise management of RC tears.
PURPOSE: Novel chip compositions comprising alkylene glycol, benefit agent and fumed silica and bar compositions containing mixtures of the chips and chips containing defined surfactant systems are provided. CONSTITUTION: Chip compositions comprise: (a) 40% to about 80% by wt. of the chip composition of a polyalkylene glycol having a molecular weight greater than about 4,000; (b) 10-40% by wt. of the chip composition of benefit agent(e.g., silicone); (c) 0.01-10% by wt. of chip composition fumed silica; (d) 0.0-10% by wt. of chip composition water; and (e) 0-15% by wt. of chip composition C8 to C22 fatty acid. An extruded bar composition is produced by using about 20-40% of the chip compositions and about 80-60 % chips comprising about 5-90% by wt. of a surfactant system being selected from the group consisting of soap, anionic surfactant, nonionic surfactant, amphoteric surfactant, zwitterionic surfactant, cationic surfactant and mixtures thereof.
This is a seamless phase 1/2, multi-center, open-label study that enrolls adults with recurrent unresectable, locally advanced, or metastatic (considered non-curative) CRC, NSCLC, PANC, OVCA, MESO or other solid tumors with MSLN expression. Subjects must be germline HLA-A\*02 heterozygous, with tumors that express MSLN and have lost HLA-A\*02 expression. The purpose of Phase 1 of this study is to determine the safety and the optimal dose of A2B694 (after PCLD) in participants with solid tumor disease. The purpose of Phase 2 of this study is to determine the further safety and efficacy (how well it treats the solid tumor disease) of A2B694.

The treatment available for these cancers and other solid tumors can be toxic, debilitating, and fatal. In the recurrent unresectable, locally advanced, or metastatic setting, the intent of standard of care treatment is typically palliative rather than curative, and has not changed significantly in several decades. A2 Bio hypothesizes that A2B694 Tmod CAR T-cell therapy will enable the killing of tumor target cells (those cells that express MSLN and have LOH for HLA-A\*02 protein). Additionally, normal healthy cells that maintain HLA-A\*02 expression and co-express MSLN (eg, lung tissue) will not be targeted due to the blocker portion of the Tmod CAR T cell that acts as a self-regulated safety switch that protects normal tissue from damage. A2 Bio believes this will provide a therapeutic safety window compared to previous solid tumor targeting therapies. This hypothesis will be explored in the study.

Participants for this study must enroll and have their T cells collected (apheresis) in the pre-screening BASECAMP-1 study (NCT04981119). T cells are collected, processed and stored for each participant. Upon disease progression the participant may screen for this study (EVEREST-2) and the participant's T cells are manufactured and then infused following PCLD regimen. There is no time requirement between the studies, and patients may go directly from BASECAMP-1 to EVEREST-2 based on their own disease course.
BACKGROUND: Most studies assessing the safety of parental drug exposures during pregnancy and around the time of conception describe the effects of maternal exposure. Recent publications have raised awareness of the need for additional research regarding the safety of paternal drug exposures on pregnancy outcomes.
OBJECTIVES: To identify and describe studies that use secondary databases in paternal drug safety studies and to describe the secondary databases that were used.
METHODS: A systematic review of studies assessing paternal medication exposure and pregnancy and infant outcomes using secondary databases was performed. In addition, the secondary databases used for these studies was described. Literature search was conducted using Embase, Web of Science, and PubMed, over the period January 1, 2012 to April 30, 2023. For each eligible study, paternal drug exposure, outcome, and data source characteristics were extracted in a data extraction form.
RESULTS: After reviewing the literature, 17 studies met inclusion criteria. The medications assessed for paternal safety were anti-rheumatic drugs (n = 10), anti-depressants (n = 3), anticonvulsants (n = 2), and anti-diabetes medications (n = 2). Pregnancy safety outcomes included congenital malformations, birth weight, and developmental disorders. The studies used five different databases across Europe and North America. The included studies used databases from Denmark (n = 12), Norway (n = 2), Sweden (n = 1), Canada (n = 1), and the United States (n = 1). The European studies utilized national patient registers that linked fathers to births and prescription histories. The North American databases used included insurance claims and electronic health records.
CONCLUSIONS: Our review shows that few studies have been completed on paternal medication exposures and pregnancy outcomes, despite the availability of secondary databases that contain data necessary to link fathers to infants. More research on the potential adverse impacts of paternal medication exposures is needed.
[Problem] The state of an oral flora not only influences the oral health status but also affects an intestinal flora. Deterioration of the intestinal flora leads to various diseases, autoimmune disorders, depression, etc. The balance of the oral flora is disrupted by the formation of an oral biofilm as well as the prolonged presence thereof. Therefore, oral biofilms become a pressing issue. [Solution] An agent for improving and maintaining an oral flora, said agent comprising an acacia bark extract as an active ingredient. This agent lowers the oral biofilm formation rate and releases biofilm-forming bacteria from the biofilm. As a result, the agent inhibits the growth of gram-negative bacteria and removes the gram-negative bacteria together with other bacteria to thereby enable the oral flora to keep a good balance.
This disclosure generally relates to the use of microorganisms to make omega-phenyl products, including omega-phenyl carboxylic acids, alcohols, amines, methyl ketones and their beta-functionalized derivatives. This is achieved by utilizing an iterative carbon chain elongation pathway that uses omega-phenyl CoA thioester primers. The core enzymes in the pathway include thiolase, dehydrogenase, dehydratase and reductase. Native or engineered thiolases catalyze the condensation of omega-phenyl CoA thioester primers with acetyl-CoA as the extender unit to generate omega-phenyl β-keto acyl-CoA. Dehydrogenase converts omega-phenyl β-keto acyl-CoA to omega-phenyl β-hydroxy acyl-CoA. Dehydratase converts omega-phenyl β-hydroxy acyl-CoA to omega-phenyl enoyl-CoA. Reductase converts omega- phenyl enoyl-CoA to omega-phenyl acyl-CoA. The platform can be operated in an iterative manner (i.e. multiple turns) by using the resulting omega-phenyl acyl-CoA as primer and acetyl-CoA as extender unit in subsequent turns of the cycle. Termination pathways acting on any of the four omega-phenyl CoA thioester intermediates terminate the platform and generate various omega-phenyl carboxylic acids, alcohols, and amines with different degrees of β -reduction.
FIELD: organic chemistry, pharmacy. SUBSTANCE: invention relates to novel derivatives of 4-oxobutanoic acid of the formula (I)   where groups A and B are taken independently each of other among mono- or bicyclic aryl group taken among phenyl and naphthyl, cycloalkyl-group with from 5 to 8 carbon atoms, saturated heterocyclic group taken among tetrahydrofuryl-group. Groups A and B can have from 1 to 3 substitutes taken among C 1 - C 6 -alkyl group, C 1 - C 6 -alkoxy-group, halogen atom or two substitutes in common mean methylenedioxy- -group. Invention relates to also a pharmaceutical composition containing the compound of the formula (I) as an active component. The proposed new derivatives of 4-oxobutanoic acid can be used for treatment of patients with diabetes mellitus. EFFECT: new compounds indicated above, valuable medicinal properties. 4 cl, 3 tbl