anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
This study was performed to investigate the protective effects of Allium ochotense on fatty liver and hepatitis in chronic alcohol-induced hepatotoxicity. The physiological compounds of a mixture of aqueous and 60% ethanol (2:8, w/w) extracts of A. ochotense (EA) were identified as kestose, raffinose, kaempferol and quercetin glucoside, and kaempferol di-glucoside by UPLC Q-TOF MSE. The EA regulated the levels of lipid metabolism-related biomarkers such as total cholesterol, triglyceride, low-density lipoprotein (LDL), and high-density lipoprotein (HDL)-cholesterol in serum. Also, EA ameliorated the levels of liver toxicity-related biomarkers such as glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and total bilirubin in serum. EA improved the antioxidant system by reducing malondialdehyde contents and increasing superoxide dismutase (SOD) levels and reduced glutathione content. EA improved the alcohol metabolizing enzymes such as alcohol dehydrogenase, acetaldehyde dehydrogenase, and cytochrome P450 2E1 (CYP2E1). Treatment with EA alleviated lipid accumulation-related protein expression by improving phosphorylation of AMP-activated protein kinase (p-AMPK) expression levels. Especially, EA reduced inflammatory response by regulating the toll-like receptor-4/nuclear factor kappa-light-chain-enhancer of activated B cells (TLR-4/NF-κB) signaling pathway. EA showed an anti-apoptotic effect by regulating the expression levels of B-cell lymphoma 2 (BCl-2), BCl-2-associated X protein (BAX), and caspase 3. Treatment with EA also ameliorated liver fibrosis via inhibition of transforming growth factor-beta 1/suppressor of mothers against decapentaplegic (TGF-β1/Smad) pathway and alpha-smooth muscle actin (α-SMA). Therefore, these results suggest that EA might be a potential prophylactic agent for the treatment of alcoholic liver disease.
FIELD: molecular medicine; pharmacology.SUBSTANCE: invention relates to the field of molecular medicine and pharmacology, namely to a liposomal form of Abies sibirica resin. A method for obtaining the liposomal form of Abies sibirica resin, which is phospholipid membrane with the inclusion of natural Abies sibirica resin (oleoresin) in amount of up to 1% by wt., is proposed including following stages: simple mixing of 0.55 g of phospholipid, 0.03 g of cholesterol, 0.04 g of a pegylating agent - up to 6% by wt. and active substance - Abies sibirica resin - up to 1% by wt. in a suitable solvent, evaporation of the solvent at a temperature above a phospholipid phase transition to obtain homogeneous lipid film, its rehydration in a medium selected from ultra-purified water or a physiological 0.9% aqueous solution of sodium chloride - up to 100% by wt., while mixing at a constant temperature above the phospholipid phase transition and subsequent dispersion of particles to a size of about 100 nm. The liposomal form of Abies sibirica resin obtained by the above-described method has an activity selected from: a function of directed delivery of biologically active substance of Abies sibirica oleoresin to the brain, antioxidant activity in vitro, cytotoxic activity in vitro against human tumor cells M-Hela. The liposomal form of Abies sibirica resin is used to ensure the activity selected from: penetration into the central nervous system (CNS), penetration into the CNS with intranasal administration, antioxidant activity in vitro, cytotoxic activity in vitro against human tumor cells M-Hela.EFFECT: above-described liposomal form of Abies sibirica resin has an increased bioavailability of Abies sibirica resin, which is water-soluble, is capable of non-invasively penetrating the CNS and at the same time has pharmacological activity, simultaneously exhibiting in vitro antioxidant properties and cytotoxic activity against cervical cancer cells M-Hela.8 cl, 15 dwg, 3 tbl, 7 ex
This is an open-label (all people know the identity of the intervention), multi-center, prospective (a study in which the participants are identified and then followed forward in time for the outcome of the study), single-arm (all participants receiving one intervention) study. Approximately 260 participants will be enrolled in this study. This study consists of two phases: screening phase and treatment phase. In the treatment phase, participants will receive escitalopram for 8 weeks: escitalopram 10 mg per day for 1 week and then the dose of escitalopram will be flexibly adjusted up to maximum of 20 mg per day for the next 7 weeks, based on the investigator's clinical judgment. Safety evaluations will include assessment of adverse events, clinical laboratory tests, electrocardiogram, vital signs, and physical examination which will be monitored throughout the study. The total study duration will be approximately 2 years.
Psoriasis is a chronic skin disease with increased risk of cardiovascular and rheumatic disease. Inhibition of the IL17/IL22/TNFα axis is beneficial, supporting a role for Th17 cells in this pathology. Herein, the inventors investigated the presence and the role of Ca v 1.4 calcium channels in Th17 cells in psoriatic patients. They demonstrated, for the first time, the Ca v 1.4 expression in RORgT +  CD4 +  cells infiltrating psoriatic skin. Nicardipine, a Ca v 1 inhibitor broadly used in cardiovascular diseases markedly reduced production of all their cytokines. The knockdown of Ca v 1.4 by shRNA also impaired TCR-induced Th17 cytokine production in Th17 cells. Finally, nicardipine reduced expressions of keratinocyte gene characteristic of psoriasic inflammation in human skin equivalents populated with Th17 cells. Altogether, these data encouraged the development of drugs inhibiting Ca v 1.4 channels in the treatment of psoriasis.
The biological clocks of the circadian timing system coordinate cellular and physiological processes and synchronize them with daily cycles. While the central clock in the suprachiasmatic nucleus (SCN) is mainly synchronized by the light/dark cycles, the peripheral clocks react to other stimuli, including the feeding/fasting state, nutrients, sleep-wake cycles, and physical activity. During the disruption of circadian rhythms due to genetic mutations or social and occupational obligations, incorrect arrangement between the internal clock system and environmental rhythms leads to the development of obesity. Desynchronization between the central and peripheral clocks by altered timing of food intake and diet composition leads to uncoupling of the peripheral clocks from the central pacemaker and to the development of metabolic disorders. The strong coupling of the SCN to the light-dark cycle creates a situation of misalignment when food is ingested during the "wrong" time of day. Food-anticipatory activity is mediated by a self-sustained circadian timing, and its principal component is a food-entrainable oscillator. Modifying the time of feeding alone greatly affects body weight, whereas ketogenic diet (KD) influences circadian biology, through the modulation of clock gene expression. Night-eating behavior is one of the causes of circadian disruption, and night eaters have compulsive and uncontrolled eating with severe obesity. By contrast, time-restricted eating (TRE) restores circadian rhythms through maintaining an appropriate daily rhythm of the eating-fasting cycle. The hypothalamus has a crucial role in the regulation of energy balance rather than food intake. While circadian locomotor output cycles kaput (CLOCK) expression levels increase with high-fat diet-induced obesity, peroxisome proliferator-activated receptor-alpha (PPARα) increases the transcriptional level of brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like 1 (BMAL1) in obese subjects. In this context, effective timing of chronotherapies aiming to correct SCN-driven rhythms depends on an accurate assessment of the SCN phase. In fact, in a multi-oscillator system, local rhythmicity and its disruption reflects the disruption of either local clocks or central clocks, thus imposing rhythmicity on those local tissues, whereas misalignment of peripheral oscillators is due to exosome-based intercellular communication.Consequently, disruption of clock genes results in dyslipidemia, insulin resistance, and obesity, while light exposure during the daytime, food intake during the daytime, and sleeping during the biological night promote circadian alignment between the central and peripheral clocks. Thus, shift work is associated with an increased risk of obesity, diabetes, and cardiovascular diseases because of unusual eating times as well as unusual light exposure and disruption of the circadian rhythm.
PROBLEM TO BE SOLVED: To obtain a transparent gel composition, having transparency, excellent in touch feeling of use without causing the lowering of viscosity and having good effects on ultraviolet light absorptivity by compounding a specific water-soluble ultraviolet light absorber with a specified polymer in combination. SOLUTION: This transparent gel composition is obtained by compounding one or more of saccharide-based water-soluble ultraviolet light absorbers with a carboxyvinyl polymer in combination. A cinnamic acid derivative, a benzophenone derivative and a 1,3-propanedione derivative are cited as the saccharide-based water-soluble ultraviolet light absorbers. A compound, etc., represented by formula I (A is a residue after removing one OH from a saccharide; R is a hydrocarbon) or formula II [B is a residue after removing (n)×OHs from a saccharide or a sugaralcohol; X is an alkoxy; (a) is 1-3; (n) is an integer] are cited as the cinnamic acid derivative and a compound, etc., represented by formula III (R<1> and R<2> are each H or OH; R<3> to R<10> are each H, OH, etc.) are cited as the benzophenone derivative.  The amount of the compounded ultraviolet light absorbers is 0.01-20.0 wt.% and that of the carboxyvinyl polymer is 0.01-5.0 wt.%.
Recurrent oral ulcer (ROU) is a prevalent and painful oral disorder with implications beyond physical symptoms, impacting quality of life and necessitating comprehensive management. Understanding the interplays between dietary factors, oral microbiota, and ROU is crucial for developing targeted interventions to improve oral and systemic health. Dietary behaviors and plant-based diet indices including the healthful plant-based diet index (hPDI) were measured based on a validated food frequency questionnaire. Saliva microbial features were profiled using 16S rRNA gene amplicon sequencing. In this cross-sectional study of 579 community-based participants (aged 22-74 years, 66.5% females), 337 participants had ROU. Participants in the highest tertile of hPDI exhibited a 43% lower prevalence of ROU (odds ratio [OR] = 0.57, 95%CI: 0.34-0.94), compared to the lowest tertile, independent of demographics, lifestyle, and major chronic diseases. Participants with ROU tended to have lower oral bacterial richness (Observed ASVs, p < 0.05) and distinct bacterial structure compared to those without ROU (PERMANOVA, p = 0.02). The relative abundances of 16 bacterial genera were associated with ROU (p-FDR < 0.20). Of these, Olsenella, TM7x, and unclassified Muribaculaceae were identified as potential mediators in the association between hPDI and ROU (all p-mediations < 0.05). This study provides evidence of the intricate interplays among dietary factors, oral microbiota, and ROU, offering insights that may inform preventive and therapeutic strategies targeting diets and oral microbiomes.
PURPOSE:To obtain the title inhibitor, containing 12-hydroxykaurenol as an essential ingredient and useful for treating diseases caused by secretory abnor mality of adrenocortical hormone, e.g. sex hormone-dependent malignant tumor, such as prostatic cancer or mammary cancer, Cushing's syndrome, etc. CONSTITUTION:A corticosteroid production inhibitor containing 12- hydroxykaurenol expressed by formula I as an essential ingredient. The com pound expressed by formula I is synthesized by producing 12-hydroxykaurene expressed by formula III from (-)-kaurene, expressed by formula II as a starting substance and available from SUGI (Japanese ceder) leaves in a large amount and using the resultant product as a raw material. The title inhibitor is prepared by formulating the essential ingredient expressed by formula I together with a suitable excipient into a dosage form suitable for oral or parenteral administra tion according to a conventional method. The daily dose of the essential ingredi ent expressed by formula I for human is 0.1-100mg/kg, preferably 10-30mg/kg.
Study participants will receive double-blind treatment with JNJ-47910382 30 mg or matching placebo. Participants in each of Panel will be treated sequentially (ie, participants in Panel 1 will be treated before participants in Panel 2, participants in Panel 2 will be treated before participants in Panel 3).
This study revolves around the optimisation of blood flow restriction (BFR) and high-intensity interval training (HIIT) protocols for the racket sport athlete. The study aims to look at the BFR + HIIT variables to induce an optimal acute training stimulus. This can be achieved with the consideration of two main research questions: (i) What is the ideal combination of BFR cuff pressure and exercise intensity (i.e. cycling) to elicit favourable training stimuli, i.e., acute responses in main outcome measures of muscular activation, muscular deoxygenation, and secondary outcome measures of heart rate (HR), blood lactate (bLa), subjective ratings of perceived exertion and discomfort?; (ii) How does BFR + HIIT compare with traditional HIIT at a similar or higher exercise intensity in terms of these acute responses?

The hypotheses for this study are: (i) BFR increases muscular deoxygenation, muscular activation when HIIT exercise is of the same intensity, (ii) however, comparing between a lower BFR + HIIT exercise intensity (e.g. 80% V̇O2max) and higher HIIT exercise intensity (e.g. 100% V̇O2max), muscular deoxygenation and activation will be similar but HR will be lower in the BFR + HIIT condition.
The present invention provides new lentiviral vectors that include an anti- repressor element (ARE) and, optionally, a scaffold attachment region (SAR). The lentivira vectors provide expression of a heterologous nucleic acid in at least 50% of the cells of multiple cell types when used for lentiviral transgenesis. In certain embodiments of the invention the heterologous nucleic acid encodes an RNAi agent such as an shRNA. The invention further provides transgenic nonhuman animals generated using a lentiviral vector that includes an ARE and optional SAR. In addition, the invention provides a variety of methods for using the vectors including for achieving gene silencing in eukaryotic cells and transgenic animals, and method's of treating disease. The invention also provides animal models ofitiuman disease in which one or more genes is functionally silenced using a lentiviral vector of the invention.
The pathological hallmarks of Alzheimer's Disease (AD) are extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles of hyperphosphorylated tau deposition in the brain together with neuroinflammation and microglial activation. These alterations lead to synaptic dysfunction, neuronal loss, and subsequently to brain circuit and brain oscillation disruption, resulting in cognitive decline. Recent studies have shown a positive effect of neural entrainment at gamma frequency (30-80 Hz). Transcranial alternating current stimulation (tACS) utilizes low amplitude alternating currents, allowing for frequency and region-specific brain oscillation entrainment showing positive results regarding improvement of cognitive functions in healthy participants and Alzheimer's Disease patients. Miamind Neurostimulator is a patient specific MRI-based 3D printed medical device that permits electrical stimulation and recording on up to 32 electrode channels and thus allows for simultaneous, multifocal, and targeted brain stimulation. tACS is non- invasive, well tolerated by users and considered safe with no persistent adverse events reported.
Cardiovascular disease (CVD) is the leading cause of death in the US and worldwide, contributing to 1 in every 4 deaths. Compared to European Americans, African Americans have higher risks for cardiometabolic conditions. Our study aim is to determine if a high-quality American Heart Association (AHA) plant-based diet intervention can promote a genetic mutational signature that is protective against CVD. We will enroll 15 Black/African American cardiac patients from Grady Memorial Hospital, Atlanta, GA. We will investigate from baseline to 3 months how the AHA plant-based diet intervention affected the regulation of several genes that are differentially expressed (DEG) and cluster together within biological pathways. We will integrate this information with WGS data, clinical factors, and ASA24-hour recalls. We expect that the AHA plant-based diet will be protective against deleterious DEG patterns that promote development of CVD. Our DEG mutational signatures in Black/African Americans with a high CVD burden can inform of changes patients can implement in their diet to decrease CVD risk burden. Our study will also fill gaps in providing new information regarding novel genomic-biological signatures with diet predictors and risk factors of CVD that can be useful in designing prevention and treatment strategies in precision medical care.
Participants randomized to the sham arm in parent study 81201887MDG2001 (NCT05811351) may have the option to receive JNJ-81201887 open-label treatment under a separate protocol after unmasking of that study; and will enter this LTE study. No intervention will be administered as part of this study.
Myddosome is an oligomeric complex required for the transmission of inflammatory signals from TLR/IL1Rs and consists of MyD88 and IRAK family kinases. However, the molecular basis for the self-assemble of Myddosome proteins and regulation of intracellular signaling remains poorly understood. Here, we identify OTUD5 acts as an essential regulator for MyD88 oligomerization and Myddosome formation. OTUD5 directly interacts with MyD88 and cleaves its K11-linked polyubiquitin chains at Lys95, Lys231 and Lys250. This polyubiquitin cleavage enhances MyD88 oligomerization after LPS stimulation, which subsequently promotes the recruitment of downstream IRAK4 and IRAK2 to form Myddosome and the activation of NF-κB and MAPK signaling and production of inflammatory cytokines. Consistently, Otud5-deficient mice are less susceptible to LPS- and CLP-induced sepsis. Taken together, our findings reveal a positive regulatory role of OTUD5 in MyD88 oligomerization and Myddosome formation, which provides new sights into the treatment of inflammatory diseases.
High-voltage-gated calcium channels have pivot role in the cellular and molecular mechanisms of various neurological disorders, including epilepsy. Similar to other calcium channels, P/Q-type calcium channels (Cav2.1) are also responsible for vesicle release at synaptic terminals. Up to date, there are very limited reports showing the mechanisms of Cav2.1 in epileptogenesis. In the present study, we investigated the anticonvulsive and neuroprotective effects of ω-agatoxin IVA, a specific Cav2.1 blocker, in a chemical kindling model of epileptogenesis. Righting reflex and inclined plane tests were used to assess motor coordination. Electroencephalography was recorded for electrophysiological monitoring of seizure activity in freely moving rats. Immunohistochemical analyses were performed for brain-derived neurotrophic factor (BDNF) and cleaved caspase-3 expressions in the prefrontal cortex, striatum, hippocampus, and thalamic nucleus. ω-Agatoxin IVA injected into the right lateral ventricle significantly prolonged the onset of seizures in a dose-dependent manner. In addition, repeated intraperitoneal administrations of ω-agatoxin IVA significantly suppressed the development of kindling and epileptic discharges without altering motor coordination. In addition, ω-agatoxin IVA significantly increased BDNF expressions, and decreased cleaved caspase-3 expressions in the brain when compared to PTZ + saline group. Our current study emphasizes the significance of the inhibition of P/Q type calcium channels by ω-agatoxin IVA, which suppresses the development of epileptogenesis and provides a new potential pathway for epilepsy treatment.
Diagnosis of Periodontitis represents the backbone of a successful periodontal treatment since the entire treatment plan, prognosis, and maintenance directly depend on the quality and precision of periodontal diagnosis. Since periodontal diagnostics is still based on clinical and radiological parameters providing limited therapeutic guidance, biomarkers have been introduced for the first time within the new classification of periodontal and peri-implant conditions as a first step towards the adoption of precision medicine concepts in periodontology. Saliva, as part of oral fluids, is an optimal biological fluid that contains locally and systemically derived mediators of periodontal disease (proteins, genetic/genomic biomarkers such as DNA and mRNA, and various metabolites that originate from the host and the bacteria) to serve as the diagnostic tool for periodontitis. The collection of saliva is safe, non-invasive, and simple, and saliva can be collected repeatedly with minimum discomfort to the patient. Single biomarker detection may not be effective enough for accurate diagnoses without false-positive or false-negative results. Periodontitis is a disease that involves complex interactions between bacteria and the host immune system. The combination of the host and bacteria-derived biomarkers, which reflect inflammation, soft tissue destruction, and bone destruction together, may be helpful in the diagnosis
The invention discloses the carrying Cap gene of porcine circovirus type 2 gene of optimization and recombinant plasmid thereof and application.The gene of the coding Porcine circovirus type 2 Cap optimized, is sequence as SEQ? ID? NO.1, SEQ? ID? NO.2 or SEQ? ID? shown in NO.3.Described recombinant plasmid is the pVAX1 carrier containing gene of the present invention.Western? Blot experiment results proved these be binned in external can effectively expression, and there is good immunogenicity.Animal immune experiment shows that the improved recombinant plasmid dna of Cap protein effectively inducing mouse and pig body can produce cell and humoral immunoresponse(HI), for the research aspect of PCV2 gene vaccine has a good application prospect.
The present invention relates to methods and compositions for the diagnosis and treatment of hematological disorders, including, but not limited to, apalstic anemia, hemophilia, sickle cell anemia, thalassisemia, blood loss and other blood disorders, e.g., blood diorders related to bone marrow irradiation or chemotherapy treatment or renal failure. The invention further provides methods for identifying a compound capable of treating a hematological disorder. The invention also provides methods for identifying a compound capable of modulating a hematopoietic cell activity. Yet further, the invention provides a method for modulating a hematopoietic cell activity. In addition, the invention provides a method for treating a subject having a hematological disorder characterized by aberrant 16319 polypeptide activity or aberrant 16319 nucleic acid expression. In another aspect, the invention provides methods for increasing hematopoietic cell proliferation in a subject and methods for modulating hematopoietic cell apoptosis in a subject.