anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) mediated immunomodulation by secreting certain bioactive cytokines has been recognized as a promising approach for disease treatment. However, microenvironmental oxygen tension affect immunomodulatory functions and activate autophagy in BMSCs. The mechanism governing BMSCs immunomodulation in hypoxia hasn't been expounded clearly. The aim of this study is to investigate the function of pathological hypoxia on immunomodulatory properties of bone marrow mesenchymal stem cells and its possible mechanism.
METHODS: BMSCs were cultured in either normoxia (21 % oxygen) or hypoxia (0.1 % oxygen) for 24 h, then electron microscopy (EM) and immunofluorescence staining were used to detect the activation of autophagy. Besides autophagy-related markers were monitored by Western blotting. Atg5 siRNA induced autophagic inhibition. Additional, gene expression levels of Real-time fluorescence quantitative PCR and Western blot were used to detect BMSCs related cytokines. Both the proliferation and apoptosis of CD4+ T cell in co-culture were detected by flow cytometry. Exogenous anti-IL-10 antibody and anti-TGF-β1 antibody were used in co-cultured BMSCs-CM and CD4+ T cells, which enabled us to assess how autophagy affected BMSCs-mediated CD4+ T cell proliferation in low oxygen tension.
RESULT: Compared with normal BMSCs, Hypo-BMSCs enhanced the immunosuppressive effect of BMSCs on CD4+ T cell proliferation, while si-atg5 weakened the inhibition of Hypo-BMSCs. Furthermore, exogenous anti-TGF-β1 antibody and the addition of anti-TGF-β1 antibody reversed the immunosuppressive ability of Hypo-BMSCs.
CONCLUSIONS: Our findings reveal that BMSCs possess significant immunosuppression on CD4+T cell through IL-10 and TGF-β1 dependent of autophagy in hypoxic microenvironment.
Patients in this group will be trained online for 6 weeks. After the online training is over, a telephone consultation service will be provided once a week for 6 weeks.
In humans and animals, the pyruvate dehydrogenase kinase (PDK) family proteins (PDKs 1-4) are excessively activated in metabolic disorders such as obesity, diabetes, and cancer, inhibiting the activity of pyruvate dehydrogenase (PDH) which plays a crucial role in energy and fatty acid metabolism and impairing its function. Intervention and regulation of PDH activity have become important research approaches for the treatment of various metabolic disorders. In this study, a small molecule (g25) targeting PDKs and activating PDH, was identified through multi-level computational screening methods. In vivo and in vitro experiments have shown that g25 activated the activity of PDH and reduced plasma lactate and triglyceride level. Besides, g25 significantly decreased hepatic fat deposition in a diet-induced obesity mouse model. Furthermore, g25 enhanced the tumor-inhibiting activity of cisplatin when used in combination. Molecular dynamics simulations and in vitro kinase assay also revealed the specificity of g25 towards PDK2. Overall, these findings emphasize the importance of targeting the PDK/PDH axis to regulate PDH enzyme activity in the treatment of metabolic disorders, providing directions for future related research. This study provides a possible lead compound for the PDK/PDH axis related diseases and offers insights into the regulatory mechanisms of this pathway in diseases.
PROBLEM TO BE SOLVED: To obtain an antitumor-active substance high in suppression rate of cancer with effectiveness less in variation and capable of oral administration, by using a hot water extract of Agaricus blazi Murr. together with royal jelly. SOLUTION: This antitumor-active substance comprises (A) a hot water extract of Agaricus blazi Murr. and (B) royal jelly. The component (A) and (B) are used together so as to supply the component (A), preferably, at 50 mg/kg/day or more and the component (B), preferably, at 10 mg/kg/day or more. This antitumor-active substance is produced by grinding the fruit body of Agaricus blazi Murr. or its dried product followed by extraction with hot water, adding royal jelly to the extract followed by concentration at reduced pressure or lyophilization.
Parents and children in the mindfulness intervention condition will be provided with a tablet and accompanying headphones, and will listen to pre-recorded audio of a mindfulness activity. There is a parent and child version of the mindfulness intervention. Both scripts were developed by Siegel and Bryson (2011), and include a parent and child version of a mindfulness activity targeting worries and anxiety. Adjustments to the child script were informed by the work of Petter and colleagues (2013). Adjustments to the parent script were informed by the work of Garland and colleagues (2015). This activity will last 5-minutes.
The cryptoglandular perianal fistula is a common benign anorectal disorder that is managed mainly with surgery and in some cases may be an extremely challenging condition. Perianal fistulas are often characterized by significantly decreased patient quality of life. Lack of fully recognized pathogenesis of this disease makes it difficult to treat it properly. Recently, adipose tissue hormones have been proposed to play a role in the genesis of cryptoglandular anal fistulas. The expression of adipose tissue hormones and epithelial-to-mesenchymal transition (EMT) factors were characterized based on 30 samples from simple fistulas and 30 samples from complex cryptoglandular perianal fistulas harvested during surgery. Tissue levels of leptin, resistin, MMP2, and MMP9 were significantly elevated in patients who underwent operations due to complex cryptoglandular perianal fistulas compared to patients with simple fistulas. Adiponectin and E-cadherin were significantly lowered in samples from complex perianal fistulas in comparison to simple fistulas. A negative correlation between leptin and E-cadherin levels was observed. Resistin and MMP2 levels, as well as adiponectin and E-cadherin levels, were positively correlated. Complex perianal cryptoglandular fistulas have a reduced level of the anti-inflammatory adipokine adiponectin and have an increase in the levels of proinflammatory resistin and leptin. Abnormal secretion of these adipokines may affect the integrity of the EMT in the fistula tract. E-cadherin, MMP2, and MMP9 expression levels were shifted in patients with more advanced and complex perianal fistulas. Our results supporting the idea of using mesenchymal stem cells in the treatment of cryptoglandular perianal fistulas seem reasonable, but further studies are warranted.
FIELD: organic chemistry, antibiotics, pharmacy. SUBSTANCE: invention relates to novel derivatives of cephalosporin of the general formula (I)   where R 1  means hydrogen atom or ester group; R 2  means the group of formulas (IIa)  , (IIb)  , (IIc)  ; Y means hydrogen atom, substituted alkyl or acyl; R 4  means hydrogen atom, phenyl, cycloalkyl or alkyl; R 5  means hydrogen atom, phenyl, cycloalkyl, lower alkyl, saturated or unsaturated 5-6-membered heterocyclyl optionally substituted with alkyl, trifluoroalkyl, oxo- or amino-group, benzothiazolyl or the group of formulas (IId)  , (IIe)  , (IIf)  ; R 7  means alkyl; R 8  means hydrogen atom, cycloalkyl or alkyl; R 9  means hydrogen atom or alkyl; R 10  means hydrogen atom, alkyl, substituted alkyl where a substituent is taken among trifluoroalkyl, pyridyl, hydroxy-, alkoxy-group, halogen atom, amino-group or residue of sulfonic acid; hydroxy-, amino-group, phenyl, alkenyl, cycloalkyl or the group of the formula N= CH-Phe where Phe means phenyl substituted with hydroxy-group; or R 9  and R 10  in common with nitrogen atom mean saturated, unsaturated or substituted 5-6-membered heterocyclyl comprising one or two nitrogen or oxygen atoms being a substituent is taken among formyl or alkyl and so on. The compound of the formula (IVa)   where R x  means the group of the formula NH- C(CH 3 ) 3  and so on; R y  means NH and R z  means hydrogen atom and so on. Invention relates to also to a pharmaceutical composition designated for treatment of diseases caused by microorganisms and comprising the compound of the formula (I) in the form of pharmaceutically acceptable salt or as a free form in combination with at least one pharmaceutical carrier or diluting agent. Invention relates to also a method of treatment of diseases caused by microorganisms that involves administration of effective compounds of the formula (I) in a person who needs with so treatment. EFFECT: new antibacterial cephalosporins indicated above, valuable medicinal properties. 13 cl, 4 tbl
Up to 6 cycles (21 days per cycle) of gemcitabine (G) and cisplatin (C) with placebo. Day 1: gemcitabine 1250 mg/ m\^2 infusion (IV), followed by cisplatin 75 mg/ m\^2 IV; Day 8: gemcitabine 1250 mg/ m\^2 IV; Days 1-21: placebo 2 tablets po bid. If the patient had radiological evidence of SD or better after completing up to 6 cycles in the Chemotherapy Phase, the patient could continue to Maintenance Phase, during which 2 placebo tablets were administered bid until criteria for withdrawal were met.
Up to 600 subjects 18-75 years will be recruited when they attend a vaccination clinic at one of the study health centers in Blantyre to receive their 1st dose of the AstraZeneca (AZ) or the Johnson and Johnson (JJ) COVID-19 vaccines. Venous blood will be collected at that time. For AZ vaccinees, at their 2nd vaccine dose, about 90 days after the 1st dose, they will be given a stool sample container. JJ vaccinees will receive the stool sample container when they receive the first vaccine dose. Two weeks after completion of the primary regimen (2nd dose of the AZ \[M3.5\] and 1st dose of the JJ vaccines \[M0.5\]), venous blood draws will be repeated and stool containers will be collected. Subsequent visits/procedures will happen at one month thereafter (M4.5 for AZ and M1.5 for JJ), and 3, 6, 9, and 12 months after the primary regimen. Venous blood will be collected at the visit 1.5, 3, 6, and 12 months after the primary regimen and capillary blood will be collected at the other visits.
BACKGROUND: Current cancer therapies often fall short in addressing the complexities of malignancies, underscoring the urgent need for innovative treatment strategies. RNA interference technology, which specifically suppresses gene expression, offers a promising new approach in the fight against tumors. Recent studies have identified a novel immunostimulatory small-interfering RNA (siRNA) with a unique sequence (sense strand, 5'-C; antisense strand, 3'-GGG) capable of activating the RIG-I/IRF3 signaling pathway. This activation induces the release of type I and III interferons, leading to an effective antiviral immune response. However, this class of immunostimulatory siRNA has not yet been explored in cancer therapy.
METHODS: IsiBCL-2, an innovative immunostimulatory siRNA designed to suppress the levels of B-cell lymphoma 2 (BCL-2), contains a distinctive motif (sense strand, 5'-C; antisense strand, 3'-GGG). Glioblastoma cells were subjected to 100 nM isiBCL-2 treatment in vitro for 48 h. Morphological changes, cell viability (CCK-8 assay), proliferation (colony formation assay), migration/invasion (scratch test and Transwell assay), apoptosis rate, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were evaluated. Western blotting and immunofluorescence analyses were performed to assess RIG-I and MHC-I molecule levels, and ELISA was utilized to measure the levels of cytokines (IFN-β and CXCL10). In vivo heterogeneous tumor models were established, and the anti-tumor effect of isiBCL-2 was confirmed through intratumoral injection.
RESULTS: IsiBCL-2 exhibited significant inhibitory effects on glioblastoma cell growth and induced apoptosis. BCL-2 mRNA levels were significantly decreased by 67.52%. IsiBCL-2 treatment resulted in an apoptotic rate of approximately 51.96%, accompanied by a 71.76% reduction in MMP and a 41.87% increase in ROS accumulation. Western blotting and immunofluorescence analyses demonstrated increased levels of RIG-I, MAVS, and MHC-I following isiBCL-2 treatment. ELISA tests indicated a significant increase in IFN-β and CXCL10 levels. In vivo studies using nude mice confirmed that isiBCL-2 effectively impeded the growth and progression of glioblastoma tumors.
CONCLUSIONS: This study introduces an innovative method to induce innate signaling by incorporating an immunostimulatory sequence (sense strand, 5'-C; antisense strand, 3'-GGG) into siRNA, resulting in the formation of RNA dimers through Hoogsteen base-pairing. This activation triggers the RIG-I signaling pathway in tumor cells, causing further damage and inducing a potent immune response. This inventive design and application of immunostimulatory siRNA offer a novel perspective on tumor immunotherapy, holding significant implications for the field.
A mechanism is provided for implementing an emergency response cognitive computing system. The emergency response cognitive computing system identifies a first party about which a communication is being performed between a caller and the emergency response system. The emergency response cognitive computing system generates, in real-time, a transcript of the communication as the communication is being conducted. The emergency response cognitive computing system performs natural language processing on the transcript of the communication to identify portions of content corresponding to medical concepts. The emergency response cognitive computing system processes patient information to identify elements of the patient information referencing concepts corresponding to medical concepts. The emergency response cognitive computing system outputs the elements of the patient information to a second party involved in the communication.
Long-term studies in animals to determine the carcinogenic potential of besifloxacin have not been performed.

No in vitro mutagenic activity of besifloxacin was observed in an Ames test (up to 3.33 mcg/plate) on bacterial tester strains Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA. However, it was mutagenic in S. typhimurium strain TA102 and E. coli strain WP2 (pKM101). Positive responses in these strains have been observed with other quinolones and are likely related to topoisomerase inhibition.

Besifloxacin induced chromosomal aberrations in CHO cells in vitro and it was positive in an in vivo mouse micronucleus assay at oral doses ≥1,500 mg/kg. Besifloxacin did not induce unscheduled DNA synthesis in hepatocytes cultured from rats given the test compound up to 2,000 mg/kg by the oral route. In a fertility and early embryonic development study in rats, besifloxacin did not impair the fertility of male or female rats at oral doses of up to 500 mg/kg/day. This dose is approximately 26,500 times higher than the mean plasma concentration measured in humans at the recommended human ophthalmic dose.
A total of 24 Chinese pregnant subjects with 34+0-35+6 GW requiring dexamethasone treatment for preterm labour with preterm prematurity in China were planned to be enrolled in this study. A total of 12 subjects receiving 5 mg dexamethasone (intramuscular injection, q12h, 4 doses) were enrolled in the full-dose group; 12 subjects receiving 2.5 mg dexamethasone (intramuscular injection, q12h, 4 doses) were enrolled in the half-dose group.
PURPOSE:To carry out the racemization of the optically active 2-(10,11-dihydro- 10-oxodibenzo[b,f]thiepin-2-yl)-propionic acid, easily, with simple operation, without converting to its derivative, by heating the acid in the presence of a strong acid. CONSTITUTION:The optically active 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2- yl)-propionic acid of formula (* represents optical activity) is racemized by heating in the presence of a strong acid such as mineral acid (e.g. hydrochloric acid) or organic sulfonic acid (e.g. methanesulfonic acid). The strong acid acts as a catalyst, and its amount is preferably 1.0-5.0mol per 1mol of the optically active compound of formula. The reaction is preferably carried out in a solvent, preferably a mixture of water and an organic acid, especially acetic acid. The reaction temperature is preferably 100-200 deg.C.
Diabetes mellitus is a growing global public health issue estimated to affect around 600 million people by 2040 [1]. It occurs in populations throughout the world, is increasing in both the developing world and high-income countries and also affects young, working-age people. Ocular involvement in diabetes occurs early in the disease and is present in over a third of diabetes mellitus Type 2 patients at the time of diagnosis. Blindness due to diabetic retinopathy (DR) remains a leading cause of adult-onset blindness, [1] which results from disruption of retinal vasculature, ischemia and its consequences and exudation causing macular edema. The prevalence of diabetic retinopathy is increasing at a greater rate than other causes of blindness including cataract, refractive errors, age-related macular degeneration and glaucoma. Compared to cataract and refractive error, management of diabetic retinopathy requires vast medical resources, including trained medical practitioners able to perform ocular injections and ophthalmologists for laser treatments and retinal surgery. This creates a significant burden on medical services as care for these patients lasts decades.
FIELD: medicine.SUBSTANCE: invention refers to medicine, specifically dermatology, and may be used for treating experimental leprous infection. For the purpose for suppression of leprous mycobacteria propagation in mice pads infected intraplantarily by Shepard's method, therapeutic agents are used. The therapeutic agents are presented by a herbal tea. The tea contains ground equal weight proportions of common licorice roots Glycyrrhiza glabra, parviflorous yarrow herb Achillea micrantha and sandy everlasting blossom Helichrisum arenarium. The tea is extracted in prepared 40% aqueous surgical ethanol in the relation of 1 portion of the raw material to 3 portions of ethanol and kept with agitation for 6 days. Then the mixture is added with an equal proportion of a buffer containing, wt %: calcium chloride 0.014, potassium chloride 0.04, potassium dihydrogen phosphate 0.006, magnesium sulphate 0.02, magnesium chloride 0.02, sodium chloride 0.08, sodium bicarbonate 0.035, disodium phosphate 0.024, glucose 0.1. The mixture is kept for another 4 days in a cool place with daily stirring, filtered andoclaved for three times at 0.5 atm for 10 minutes; the prepared extract is introduced into experimental animals in dose 0.4-0.6 mg/kg of body weight daily through a probe into oesophagus.EFFECT: presented invention provides higher therapeutic effectiveness ensured by substantial suppression of leprous mycobacteria growth in mice pads, higher activity of completed phagocytosis M leprae in animal macrophagues, optimal selection of doses with no side effects.5 ex, 10 tbl
The dose will be 1×106 DSC/kg bodyweight, at least 2 doses at least one week apart. Within the first 28 days, patients meeting criteria of aGvHD disease progression, mixed response or no response, may be given additional weekly doses of DSC until satisfactory response (ie: CR) are reached (max 4 doses in total).
In PROactive (the Prospective Pioglitazone Clinical Trial in Macrovascular Events), 5238 patients with type 2 diabetes and a history of macrovascular disease were randomized to pioglitazone(N=2605), force-titrated up to 45 mg daily or placebo (N=2633) in addition to standard of care. During a mean follow-up of 34.5 months, the incidence of bone fracture in females was 5.1% (44/870) for pioglitazone versus 2.5% (23/905) for placebo. This difference was noted after the first year of treatment and persisted during the course of the study. The majority of fractures observed in female patients were nonvertebral fractures including lower limb and distal upper limb. No increase in the incidence of fracture was observed in men treated with pioglitazone(1.7%) versus placebo (2.1%). The risk of fracture should be considered in the care of patients, especially female patients, treated with pioglitazone and attention should be given to assessing and maintaining bone health according to current standards of care.
The T\&T intervention aims to prevent teenage pregnancy and promote sexual health by providing young women at risk of teenage pregnancy with regular and direct contact with a toddler and combines this with 12 modules of group-based personal-development sessions involving communication skills, anger management, discussion of positive sexual health and relationships, culminating in an accredited National Award in Interpersonal Skills. One-to-one life coaching is also provided. The intervention consists of 20 weekly afternoon sessions run in nurseries near to the secondary schools from which participating young women are recruited.
Studies to date indicate that there may be a dose-sparing effect with the use of QS21. In animal studies, when QS21 has been employed as an adjuvant, it shifted both the dose response curve and allowed less antigen to elicit equivalent binding antibody titers to the rgp120 protein. There may also be an acceleration in the course of antibody response after both the first and the second immunizations. Although the final titers in response to vaccine given in both alum and QS21 appear similar after 3 doses in humans, this plateau may be reached more readily, and with a lower antigen dose, when using QS21 as an adjuvant. In addition, it has been established that using a lower dose of antigen may elicit an immune response which is characterized by lymphoproliferation and production of TH1-like cytokines such as INF-gamma, interleukin-2, interleukin-4, interleukin-5 and interleukin-10.

Patients will be recruited and screened and those determined as eligible will be enrolled in the study. Initially, 5 patients will be randomized into each combination of MN rsgp 120/HIV-1 dose and adjuvant, QS21 or alum, along with 2 controls for each adjuvant group. An additional 10 patients will be randomized equally between the QS21 and alum arms to the lowest dose group having 2 or more responders defined as an MN Vital Dye neutralization titer greater than or equal to 10 measured at 2 weeks after the second vaccination. 1 additional control will also be randomized to each adjuvant group. If neither dose has 2 or more responders, no additional patients will be enrolled. Patients will receive their randomly assigned injections at months 0, 1 and 6. Patients will be tested for DTH to MN rsgp 120 at 12 months.
Sham intervention: Arm cuff placement but without inflation during a 40 minute period. A curtain will obscure the patient from the clinical team during this time. Arm cuff placement, no inflation.
FIELD: medicine. SUBSTANCE: aqueous solution of methylcellulose heated to 40-50 C is applied on heated preliminary to 40-50 C paper linen. Then mustard powder is sprayed on it, mustard's expense being removed. The process is followed by pulling linen between shafts heated to 50-60 C and by drying at 50-60 C. Device for manufacturing sinapism has tape-transport mechanism, bunker for aqueous solution of methylcellulose and drying chamber being displaced above it. Air heater for heating paper linen is displaced in front of bunker; vibrating screen, suction fan and rolling shaft are displaced between bunker and drying chamber. EFFECT: improves efficiency of the method. 1 tbl
Toclizumab will be administered on Day 0. The administration of tocilizumab will be every 2 weeks for a total of 8 doses.