anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Reperfusion therapy after ischemic stroke often causes brain microvascular injury. However, the underlying mechanisms are unclear.
METHODS: Transcriptomic and proteomic analyses were performed on human cerebral microvascular endothelial cells following oxygen-glucose deprivation (OGD) or OGD plus recovery (OGD/R) to identify molecules and signaling pathways dysregulated by reperfusion. Major findings were further validated in a mouse model of cerebral ischemia and reperfusion.
RESULTS: Transcriptomic analysis identified 390 differentially expressed genes (DEGs) between the OGD/R and OGD group. Pathway analysis indicated that these genes were mostly associated with inflammation, including the TNF signaling pathway, TGF-β signaling pathway, cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, and NF-κB signaling pathway. Proteomic analysis identified 201 differentially expressed proteins (DEPs), which were primarily associated with extracellular matrix destruction and remodeling, impairment of endothelial transport function, and inflammatory responses. Six genes (DUSP1, JUNB, NFKBIA, NR4A1, SERPINE1, and THBS1) were upregulated by OGD/R at both the mRNA and protein levels. In mice with cerebral ischemia and reperfusion, brain TNF signaling pathway was activated by reperfusion, and inhibiting TNF-α with adalimumab significantly attenuated reperfusion-induced brain endothelial inflammation. In addition, the protein level of THBS1 was substantially upregulated upon reperfusion in brain endothelial cells and the peri-endothelial area in mice receiving cerebral ischemia.
CONCLUSION: Our study reveals the key molecular signatures of brain endothelial reperfusion injury and provides potential therapeutic targets for the treatment of brain microvascular injury after reperfusion therapy in ischemic stroke.
PURPOSE: Model systems for diseases are provided that involve defects in the function of mitochondria, where those defects arise from defects in the genes of those mitochondria. CONSTITUTION: A methods are for detecting such mutations as a diagnostic for late onset diabetes, either before or after the onset of clinical symptoms. More specifically, the present invention provides a method for detecting the presence or risk of developing diabetes mellitus in a human by determining the presence in a biological sample from a human of at least one mitochondrial mutation in an ATP synthase gene or in a tRNA-lysine (tRNALYs) gene that correlates with the presence of or risk of developing diabetes mellitus. The invention further provides, but need not be limited to, particular nucleotide positions within ATP synthase gene sequences and in tRNALYs gene sequences where mutations that are silent mutations, missense mutations, or combinations thereof, may occur. In one embodiment, the invention provides a method for detecting the presence or risk of developing diabetes by determining the presence in a biological sample of at least one mitochondrial mutation that correlates with the presence or risk of developing diabetes mellitus. In various embodiments, the mutation is determined by hybridization with oligonucleotide probes, by ligation reaction, by polymerase chain reaction and variations thereof, or by single nucleotide primer-guided extension.
PULMICORT FLEXHALER should be administered twice daily by the orally inhaled route only. After inhalation, the patient should rinse the mouth with water without swallowing [see Patient Counseling Information (17.1)]. 

Patients should be instructed to prime PULMICORT FLEXHALER prior to its initial use, and instructed to inhale deeply and forcefully each time the device is used. 

The safety and efficacy of PULMICORT FLEXHALER when administered in excess of recommended doses have not been established. 

After asthma stability has been achieved, it is desirable to titrate to the lowest effective dosage to reduce the possibility of side effects. For patients who do not respond adequately to the starting dose after 1-2 weeks of therapy with PULMICORT FLEXHALER, increasing the dose may provide additional asthma control.
Disclosed are multilayered liposomes for transdermal absorption and a method of preparing the liposomes. The multilayered liposomes are prepared using a mixture of oil-phase components comprising squalane, sterols, ceramides, neutral lipids or oils, fatty acids and lecithins, is 200 to 5000 nm in particle size, and is capable of entrapping a physiologically active substance. The multilayered liposomes entrap a larger amount of a physiologically active substance and are structurally stable when encapsulating the physiologically active substance, compared to unilamellar liposomes. Also, they are prepared by a simple and cost-effective process not using a high-pressure homogenizer but using a general homo mixer. Further, since the multilayered liposomes are prepared in a larger size than the intercellular spaces in the stratum corneum, they overcome the tension of surrounding cells when passing through the intercellular spaces and are thus able to penetrate into the dermal layer, compared to nano-sized unilamellar liposomes. Thus, the multilayered liposomes are useful for enhancing the transdermal absorption of physiologically active substances.
The oral LD50 of isotretinoin is greater than 4000 mg/kg in rats and mice (>600 times the recommended clinical dose of 1 mg/kg/day after normalization of the rat dose for total body surface area and >300 times the recommended clinical dose of 1 mg/kg/day after normalization of the mouse dose for total body surface area) and is approximately 1960 mg/kg in rabbits (653 times the recommended clinical dose of 1 mg/kg/day after normalization for total body surface area). In humans, overdosage has been associated with vomiting, facial flushing, cheilosis, abdominal pain, headache, dizziness, and ataxia. These symptoms quickly resolve without apparent residual effects.

Isotretinoin causes life-threatening birth defects at any dosage (see Boxed CONTRAINDICATIONS AND WARNINGS). Patients who can become pregnant who present with isotretinoin overdose must be evaluated for pregnancy. Patients who are pregnant should receive counseling about the risks to the fetus, as described in the Boxed CONTRAINDICATIONS AND WARNINGS. Non-pregnant patients must be warned to avoid pregnancy for at least one month and receive contraceptive counseling as described in PRECAUTIONS. Educational materials for such patients can be obtained by calling the manufacturer. Because an overdose would be expected to result in higher levels of isotretinoin in semen than found during a normal treatment course, male patients should use a condom, or avoid reproductive sexual activity with a patient who is or might become pregnant, for one month after the overdose. All patients with isotretinoin overdose should not donate blood for at least one month.
Docetaxel, 60 mg/m2/day, IV, every 3 weeks; cisplatin, 60 mg/m2/day, IV, every 3 weeks; capecitabine, 825 mg/m2, orally, twice daily for 2 weeks, followed by 1 week of rest in each cycle. Study drugs were administered for at least 24 weeks.
ETHNOPHARMACOLOGICAL RELEVANCE: Alpha 7 nicotinic acetylcholine receptor (α7nAChR)-mediated astrocytic activation is closely related to central sensitization of chronic migraine (CM). Xiongzhi Dilong decoction (XZDL), originated from Xiongzhi Shigao decoction of Yi-zong-jin-jian, has been confirmed to relieve CM in experiment and clinic. However, its underlying mechanism for treating CM has not been elucidated.
AIM OF THE STUDY: To reveal the underlying mechanisms of XZDL to alleviate CM in vivo focusing mainly on α7nAChR-mediated astrocytic activation and central sensitization in TNC.
MATERIALS AND METHODS: CM rat model was established by subcutaneous injection of nitroglycerin (NTG) recurrently, and treated with XZDL simultaneously. Migraine-like behaviors of rats (ear redness, head scratching, and cage climbing) and pain-related reactions (mechanical hind-paw withdrawal threshold) of rats were evaluated before and after NTG injection and XZDL administration at different points in time for nine days. The immunofluorescence single and double staining were applied to detect the levels of CGRP, c-Fos, GFAP and α7nAChR in NTG-induced CM rats. ELISA kits were employed to quantify levels of TNF-α, IL-1β, and IL-6 in medulla oblongata of CM rats. The expression levels of target proteins were examined using western blotting. Finally, methyllycaconitine citrate (MLA, a specific antagonist of α7nAChR) was applied to further validate the mechanisms of XZDL in vivo.
RESULTS: XZDL significantly attenuated the pain-related behaviors of the NTG-induced CM rats, manifesting as constraints of aberrant migraine-like behaviors including elongated latency of ear redness and decreased numbers of head scratching and cage climbing, and increment of mechanical withdrawal threshold. Moreover, XZDL markedly lowered levels of CGRP and c-Fos, as well as inflammatory cytokines (IL-1β, IL-6 and TNF-α) in CM rats. Furthermore, XZDL significantly enhanced α7nAChR expression and its co-localization with GFAP, while markedly inhibited the expression of GFAP and the activation of JAK2/STAT3/NF-κB pathway in the TNC of CM rats. Finally, blocking α7nAChR with MLA reversed the effects of XZDL on astrocytic activation, central sensitization, and the pain-related behaviors in vivo.
CONCLUSION: XZDL inhibited astrocytic activation and central sensitization in NTG-induced CM rats by facilitating α7nAChR expression and suppressing JAK2/STAT3/NF-κB pathway, implying that the regulation of α7nAChR-mediated astrocytic activation represents a novel mechanism of XZDL for relieving CM.
Cyclic peptides represented by general formula (I) and having VLA-4 adhesion inhibitory activities, and the use thereof as remedies for allergic inflammations or hepatitis. In said formula, A and F represent each Cys, Asp, etc.; B represents Ala etc.; C represents Asp analog etc.; D represents Tyr etc.; E represents Leu etc.; G represents a disulfide or amide linkage; R1 represents hydrogen or acyl; and R2 represents hydrogen or alkyl.
Subjects will consume a high fat breakfast, containing of sausage rolls. Energy content of the breakfast will be set to 50 % of the recommended daily calorie intake (BMR times 1.3).
OBJECTIVES: False lumen (FL) thrombosis status for Stanford type B aortic dissection (TBAD) after thoracic endovascular aortic repair (TEVAR) is critical for evaluating aortic remodeling and long-term prognosis. This study aimed to monitor the morphology evolution of partial FL thrombosis (PFLT) and its hemodynamic conditions through an innovative approach, providing a re-intervention strategy from both morphologic and hemodynamic perspectives.
METHODS: Three-dimensional geometries are extracted from a five-year follow-up of CTA images for TBAD after TEVAR. The morphology and hemodynamics of PFLT are comprehensively analyzed based on patient-specific reconstructions and computational fluid dynamics (CFD). The impact of various strategies treating risk factors of PFLT, including proximal entry closure, left renal artery stenting, or accessory renal artery embolism on hemodynamics is assessed.
RESULTS: The introduced morphologic approaches appropriately reflected the evolution of PFLT. Gradual dilation of FL (surface area from 82.63cm2 to 98.84cm2, volume from 45.12 mL to 63.40 mL, increase in distal tear (from 3.72 cm to 4.32 cm), and fluctuation of thrombosis-blood lumen boundary are observed. For further surgical preparation in the absence of unanimously recognized re-intervention indicators, velocity and wall shear stress distributions reveal different simulated re-interventions have distinctly suppressive effects on hemodynamic conditions within the PFLT, providing valuable insights for further surgical preparation.
CONCLUSIONS: The present study demonstrates a re-intervention strategy for PFLT in TBAD patients after TEVAR utilizing morphologic and hemodynamic analyses. Acknowledging the deterioration of PFLT may result in adverse long-term outcomes, this strategy might offer an alternative approach for clinical monitoring and management of related patients.
PURPOSE: Radioresistance of lung cancer poses a significant challenge when it comes to the treatment of advanced, recurrent, and metastatic cases. Ovarian tumor domain ubiquitin aldehyde binding 1 (OTUB1) is a key member of the deubiquitinase OTU superfamily. This protein is involved in various cellular functions, including cell proliferation, iron death, lipid metabolism, and cytokine secretion as well as immune response processes. However, its specific role and molecular mechanism in lung cancer radioresistance remain to be clarified.
METHODS AND MATERIALS: The expression levels of OTUB1 in paired lung cancer tissues were determined by immunohistochemistry. In vitro and in vivo experiments were conducted to investigate the impact of OTUB1 on the growth and proliferation of lung cancer. Coimmunoprecipitation and Western blotting techniques were performed to examine the interaction between OTUB1 and CHK1. The DNA damage response was measured by comet tailing and immunofluorescence staining. KEGG pathways and Gene Ontology terms were analyzed based on RNA sequencing.
RESULTS: Our findings reveal a high frequency of OTUB1 overexpression, which is associated with an unfavorable prognosis in patients with lung cancer. Through comprehensive investigations, we demonstrate that OTUB1 depletion impairs the process of DNA damage repair and overcomes radioresistance. In terms of the underlying mechanism, our study uncovers that OTUB1 deubiquitinates and stabilizes CHK1, which enhances CHK1 stability, thereby regulating DNA damage and repair. Additionally, we identify CHK1 as the primary downstream effector responsible for mediating the functional effects exerted by OTUB1 specifically in lung cancer. Importantly, OTUB1 has the potential to be a valuable marker for improving the efficacy of radiation therapy for lung adenocarcinoma.
CONCLUSIONS: These findings unveil a novel role for OTUB1 in enhancing radioresistance by deubiquitination and stabilization of the expression of CHK1 in lung cancer and indicate that targeting OTUB1 holds great potential as an effective therapeutic approach for enhancing the efficacy of radiation therapy in lung cancer.
Substance P (SP) plays a crucial role in pain modulation, with significant implications for major depressive disorder (MDD), anxiety disorders, and post-traumatic stress disorder (PTSD). Elevated SP levels are linked to heightened pain sensitivity and various psychiatric conditions, spurring interest in potential therapeutic interventions. In chronic pain, commonly associated with MDD and anxiety disorders, SP emerges as a key mediator in pain and emotional regulation. This review examines SP's impact on pain perception and its contributions to MDD, anxiety disorders, and PTSD. The association of SP with increased pain sensitivity and chronic pain conditions underscores its importance in pain modulation. Additionally, SP influences the pathophysiology of MDD, anxiety disorders, and PTSD, highlighting its potential as a therapeutic target. Understanding SP's diverse effects provides valuable insights into the mechanisms underlying these psychiatric disorders and their treatment. Further research is essential to explore SP modulation in psychiatric disorders and develop more effective treatment strategies.
PURPOSE: A microgranule containing stabilized 5-pirrolyl-2-pyridylmethylsulfinylbenzimidazole derivative (formula 1) is useful as anti-ulcer agent and very unstable in acid is provided. The microgranule uses alkali compound as stabilizer and water soluble high polymer as binder to maximize stability thereof. CONSTITUTION: A microgranule contains 5-pirrolyl-2-pyridylmethylsulfinylbenzimidazole derivative as effective component, 0.2-7.0 times of alkali compound as stabilizer based on molar amount of the effective component and 0.1-50 wt.% of water soluble high polymer as binder based on the total weight of microgranule. The water soluble high polymer can be hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, sodium alginate, alginic acid etc.. The alkali compound can be magnesium oxide, sodium phosphate dibasic, sodium phosphate monobasic, magnesium hydroxide, aluminium hydroxide, aluminium carbonate etc.. The microgranule having maximized stability enables the effective component to be stored at room temperature while transporting for industrial use.
Drug-resistant epilepsy presents significant challenges in treating epileptic patients, leading to recurrent seizures and necessitating the use of polypharmacy with anti-epileptic drugs. Both of these conditions contribute to increased oxidative stress, which is detrimental to the brain. The aim of this study was to determine the role of vitamins C and E in reducing oxidative stress and seizure frequency in drug-resistant epileptic patients. This was a double-blinded, randomized clinical trial with a placebo, parallel design, and block randomization. The subjects were drug-resistant epileptic patients aged 1-18 years who received routine treatment. Randomization was performed on 100 patients who were divided into the treatment or placebo groups. The patients received a combination of vitamin C (100 mg/day) and vitamin E (200 IU/day for those <5 years or 400 IU/day for those ≥5 years) or a placebo for eight weeks. Malondialdehyde (MDA) levels and seizure frequency were measured prior to and after the intervention. A total of 42 and 46 patients were followed till the end of the study in the intervention and placebo groups, respectively. Our data indicated that the MDA levels prior to treatment were not significantly different between the treatment and placebo groups (0.901 vs 0.890 mmol/mL, p=0.920) and were significantly reduced after the treatment in both the treatment group (p<0.001) and placebo group (p=0.028). The changes in MDA levels (between post- and pre-treatment) were also not significantly different between the two groups (p=0.181). Our per-protocol analysis indicated that the reduction in seizure frequency was significantly higher in the treatment group compared to the placebo group (95% vs 35%, p<0.001), with 92% and 60% relative and absolute risk reduction, respectively. The intention-to-treat analysis also indicated that the reduction in seizure frequency was significantly higher in the intervention group than in the control group (80% vs 32%, p<0.001), with relative and absolute risk reduction of 70% and 48%, respectively. There was no significant relationship between changes in MDA levels and seizure frequency in either group. In conclusion, vitamins C and E could reduce seizure frequency and, therefore, could be considered as adjuvant therapy in drug-resistant epileptic patients.
Drugs that interfere with serotonin reuptake, including SAVELLA, may increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Based on data from published observational studies, exposure to SNRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Use in Specific Populations (8.1)]. Bleeding events related to SSRIs and SNRIs have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages.

Inform patients about the increased risk of bleeding associated with the concomitant use of SAVELLA and NSAIDs, aspirin, or other drugs that affect coagulation [see Drug Interactions (7.7)].
Adaptation to hypoxia is a major challenge for the survival of Mycobacterium tuberculosis (Mtb) in vivo. Interferon (IFN)-γ-producing CD8+ T cells contribute to control of Mtb infection, in part by promoting antimicrobial activities of macrophages. Whether Mtb counters these responses, particularly during hypoxic conditions, remains unknown. Using metabolomic, proteomic and genetic approaches, here we show that Mtb induced Rv0884c (SerC), an Mtb phosphoserine aminotransferase, to produce D-serine. This activity increased Mtb pathogenesis in mice but did not directly affect intramacrophage Mtb survival. Instead, D-serine inhibited IFN-γ production by CD8+ T cells, which indirectly reduced the ability of macrophages to restrict Mtb upon co-culture. Mechanistically, D-serine interacted with WDR24 and inhibited mTORC1 activation in CD8+ T cells. This decreased T-bet expression and reduced IFN-γ production by CD8+ T cells. Our findings suggest an Mtb evasion mechanism where pathogen metabolic adaptation to hypoxia leads to amino acid-dependent suppression of adaptive anti-TB immunity.
PROBLEM TO BE SOLVED: To obtain an epidermal cornification accelerator which contains a substance relating to silicic acid, has an action to promote the cornification of epidermal cells to restore the barrier function of skin and is effective for atopic dermatitis, psoriasis, xeroderma, skin roughening, dandruff, lip roughening and the like. SOLUTION: This epidermal cornification accelerator contains 0.1-99wt.%, preferably 5-60wt.% of a substance relating to silicic acid, for example, silicic acid, metasilicic acid, orthosilicic acid, as an active ingredient. When this cornification accelerator is adapted to cosmetics or the like, an acid such as citric acid is preferably employed to adjust the pH to 2-10. The does as a skin preparation for external use or as a cosmetic is percutaneously 1-50mg every application in a formulation. When a bath article is formulated, the dose of the accelerator is 1-5,000mg/l in the bath water. When it is added to a cell culture system, the dose is 1-100,000μM.
The invented oral liquid uses tortoise as main raw material and matches longan pulp, tremella, jujube, honey and syrup, the weight percentage of these components are separately as 5-50, 0.5-12, 1.5-15, 1.5-15, 4-20, 9-30 and distilled water residue. The productive method of above mentioned product consists of cleaning, preboiling, extracting, blending, bottling and sterilizing etc. processes. Its feature is that the tortoise must be pretreated before preboiling, multiple times of filtering and low temp. treatment are arranged in whole productive process, the effective components of tortoise etc. raw materials must be allsidely extracted. The turbid precipitous phenominon occured in available peculiar oral liquid has been overcome, and the local flavour is peculiar.
ASCOMP with Codeine is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

The codeine in ASCOMP with Codeine may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Regularly evaluate patients with biliary tract disease, including acute pancreatitis for worsening symptoms.

Patients with a history of active peptic ulcer disease should avoid using aspirin, which can cause gastric mucosal irritation and bleeding.

The aspirin in ASCOMP with Codeine can cause GI side effects including stomach pain, heartburn, nausea, vomiting, and gross GI bleeding. Although minor upper GI symptoms, such as dyspepsia, are common and can occur anytime during therapy, physicians should remain alert for signs of ulceration and bleeding, even in the absence of previous GI symptoms. Physicians should inform patients about the signs and symptoms of GI side effects and what steps to take if they occur.
The placebo-controlled intervention is one dose (100 mL) NaCl 0.9% intravenously administered after confirmation of progressive dyspnoea. Infusion time: 60 min. The procedure is repeated once if no improvement in the 8-point WHO scale is observed.