Syringin: a naturally occurring compound with medicinal properties.

Syringin, a phenylpropanoid glycoside, is widely distributed in various plants, such as Acanthopanax senticosus (Rupr. et Maxim.) Harms, Syringa reticulata (BL) Hara var. mandshurica (Maxim.) Hara, and Ilex rotunda Thumb. It serves as the main ingredient in numerous listed medicines, health products, and foods with immunomodulatory, anti-tumor, antihyperglycemic, and antihyperlipidemic effects. This review aims to systematically summarize syringin, including its physicochemical properties, plant sources, extraction and separation methods, total synthesis approaches, pharmacological activities, drug safety profiles, and preparations and applications. It will also cover the pharmacokinetics of syringin, followed by suggestions for future application prospects. The information on syringin was obtained from internationally recognized scientific databases through the Internet (PubMed, CNKI, Google Scholar, Baidu Scholar, Web of Science, Medline Plus, ACS Elsevier, and Flora of China) and libraries. Syringin, extraction and separation, pharmacological activities, preparations and applications, and pharmacokinetics were chosen as the keywords. According to statistics, syringin can be found in 23 families more than 60 genera, and over 100 species of plants. As a key component in many Chinese herbal medicines, syringin holds significant research value due to its unique sinapyl alcohol structure. Its diverse pharmacological effects include immunomodulatory activity, tumor suppression, hypoglycemic action, and hypolipidemic effects. Additionally, it has been shown to provide neuroprotection, liver protection, radiation protection, cardioprotection, and bone protection. Related preparations such as Aidi injection, compound cantharidin capsule, and Tanreqing injection have been widely used in clinical settings. Other studies on syringin such as extraction and isolation, total synthesis, safety profile assessment, and pharmacokinetics have also made progress. It is crucial for medical research to deeply explore its mechanism of action, especially regarding immunity and tumor therapy. Meanwhile, more robust support is needed to improve the utilization of plant resources and to develop extraction means adapted to the needs of industrial biochemistry to further promote economic development while protecting people's health.

Rh(III)-catalyzed [4 + 1] annulation of 1-arylindazolones with alkynyl cyclobutanols: access to indazolo[1,2-a]indazolones.

A convenient and efficient synthesis of structurally diverse indazolo[1,2-a]indazolones via a Rh(III)-catalyzed [4 + 1] annulation of 1-arylindazolones with alkynyl cyclobutanols has been achieved by combining C-H and C-C bond cleavage. This cascade reaction features readily available starting materials, good functional group tolerance, broad substrate scope, and excellent atom-economy.

Spiro-buckybowls: Synthesis and Selective Transformations toward Chiral and Nonlinear Optical Polycycles.

Integration of spirocycles with buckybowls is a promising strategy to construct three-dimensional (3D) curved π-systems and to endow distinctive physicochemical features arising from buckybowls. Herein, a series of carbon-bridged spiro-type heterosumanenes (spiro-HSEs) were synthesized by combining 9,9'-spirobifluorene and dichalcogenasumanenes (DCSs). It is found that spiro-conjugation plays an important role in the geometric and electronic structures of spiro-HSEs. The bowl depth of DCSs moiety becomes larger in the spiro-HSEs. Owing to the Jahn-Teller (J-T) effect, two DCSs segments of spiro-HSEs have different bowl depths accompanied with the unequal distribution of charge in radical cation state. Taking advantage of the typical reactions of DCSs, selective transformations of spiro-HSEs have been adopted in accordance to the nature of chalcogen atoms (S, Se, Te) to bestow the value-added functionalities. The emissive property is enhanced by converting the thiophene rings of S-doped spiro-HSE into thiophene S,S-dioxides. A chiroptical polycycle could be produced by ring-opening of the edge benzene of Se-doped spiro-HSE. The covalent adduct of Te-doped spiro-HSE with Br2 forms non-centrosymmetric halogen-bonded networks, resulting in the high performance second-order nonlinear optics (NLO).

Impact of Extracellular Matrix-Related Genes on the Tumor Microenvironment and Prognostic Indicators in Esophageal Cancer: A Comprehensive Analytical Study.

Esophageal cancer is a major global health challenge with a poor prognosis. Recent studies underscore the extracellular matrix (ECM) role in cancer progression, but the full impact of ECM-related genes on patient outcomes remains unclear. Our study utilized next-generation sequencing and clinical data from esophageal cancer patients provided by The Cancer Genome Atlas, employing the R package in RStudio for computational analysis. This analysis identified significant associations between patient survival and various ECM-related genes, including IBSP, LINGO4, COL26A1, MMP12, KLK4, RTBDN, TENM1, GDF15, and RUNX1. Consequently, we developed a prognostic model to predict patient outcomes, which demonstrated clear survival differences between high-risk and low-risk patient groups. Our comprehensive review encompassed clinical correlations, biological pathways, and variations in immune response among these risk categories. We also constructed a nomogram integrating clinical information with risk assessment. Focusing on the TENM1 gene, we found it significantly impacts immune response, showing a positive correlation with T helper cells, NK cells, and CD8+ T cells, but a negative correlation with neutrophils and Th17 cells. Gene Set Enrichment Analysis revealed enhanced pathways related to pancreatic beta cells, spermatogenesis, apical junctions, and muscle formation in patients with high TENM1 expression. This research provides new insights into the role of ECM genes in esophageal cancer and informs future research directions.

Randomized Phase II Trial of Immunotherapy-Based Total Neoadjuvant Therapy for Proficient Mismatch Repair or Microsatellite Stable Locally Advanced Rectal Cancer (TORCH).

PURPOSE: To assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). PATIENTS AND METHODS: We conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT. RESULTS: Of the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis (P < .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and remained disease free. The most frequent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. Patients in group A had higher rate of cCR (43.5% v 35.6%) at restaging and lower rate of grade 3 to 4 thrombocytopenia (24.2% v 33.9%) during neoadjuvant treatment. CONCLUSION: The iTNT regimens remarkably improved CR rates in pMMR/MSS LARC compared with historical benchmark with acceptable toxicity. Up-front SCRT followed by immunochemotherapy was selected for future definitive study.

A comprehensive overview of the molecular features and therapeutic targets in BRAFV600E-mutant colorectal cancer.

As one of the most prevalent digestive system tumours, colorectal cancer (CRC) poses a significant threat to global human health. With the emergence of immunotherapy and target therapy, the prognosis for the majority of CRC patients has notably improved. However, the subset of patients with BRAF exon 15 p.V600E mutation (BRAFV600E) has not experienced remarkable benefits from these therapeutic advancements. Hence, researchers have undertaken foundational investigations into the molecular pathology of this specific subtype and clinical effectiveness of diverse therapeutic drug combinations. This review comprehensively summarised the distinctive molecular features and recent clinical research advancements in BRAF-mutant CRC. To explore potential therapeutic targets, this article conducted a systematic review of ongoing clinical trials involving patients with BRAFV600E-mutant CRC.

In silico degradation of fluoroquinolones by a microalgae-based constructed wetland system.

Fluoroquinolone antibiotics (FQs) have been used worldwide due to their extended antimicrobial spectrum. However, the overuse of FQs leads to frequent detection in the environment and cannot be efficiently removed. Microalgae-based constructed wetland systems have been proven to be a relatively proper method to treat FQs, mainly by microalgae, plants, microorganisms, and sediments. To improve the removal efficiency of microalgae-constructed wetland, a systematic molecular design, screening, functional, and risk evaluation method was developed using three-dimensional quantitative structure-activity relationship models, molecular dynamics simulation, molecular docking, and TOPKAT approaches. Five designed ciprofloxacin alternatives with improved bactericidal effects and lower human health risks were found to be more easily degraded by microalgae (16.11-167.88 %), plants (6.72-58.86 %), microorganisms (9.10-15.02 %), and sediments (435.83 %-1763.51 %) compared with ciprofloxacin. According to the mechanism analysis, the removal effect of the FQs can be affected via changes in the number, bond energy, and molecular descriptors of favorable and unfavorable amino acids. To the best of our knowledge, this is the first comprehensive study of improving the microalgae, plants, microorganisms, and sediment removal efficiency of FQs in constructed wetlands, which provides theoretical support for the treatment of FQ pollution.

Organocatalyzed Asymmetric Michael Addition of 3-Fluorooxindole to Vinylidene Bisphosphonates.

Both the 3-fluorooxindole and germinal bisphosphonate structural motifs are prevalent in bioactive molecules because of their associated biological activities. We describe an approach to accessing 3,3-disubstituted 3-fluorooxindoles bearing a geminal bisphosphate fragment through a highly enantioselective Michael addition reaction between 3-fluorooxindoles and vinylidene bisphosphonates. These reactions are catalyzed by a commercially available cinchona alkaloid catalyst, have a broad substrate scope concerning 3-fluorooxindoles, and provide the corresponding addition products in a yield of up to 95% with an enantiomeric excess of up to 95%. A reasonable reaction pathway to explain the observed stereochemistry is also proposed.

Seed germination ecology of endangered plant Horsfieldia hainanensis Merr. In China.

BACKGROUND: Horsfieldia hainanensis Merr., an indicator species of China's humid tropical rainforests, is endangered due to difficulties with population regeneration. In this study, the biological characteristics and germination adaptability of the seeds were studied for the first time, in order to provide a basis for analyzing the causes of endangerment and strategies for the artificial cultivation of H. hainanensis. The effects of biological characteristics (population, arils, seed coat, seed weight, seed moisture content) and environmental factors (temperature, light, drought, substrate, burial depth) on seed germination and seedling growth of H. hainanensis were studied. RESULTS AND DISCUSSION: The fruits were found to be capsules containing seeds wrapped in a pericarp and fleshy aril, which provide protection and assist in seed dispersal, but also pose risks to the seeds, as the peel and fleshy aril can become moldy under high temperature and humidity conditions. There were significant differences in fruit morphology and germination characteristics among different populations, and the seed quality of populations in Niandian village, Daxin County, Chongzuo City, Guangxi Zhuang Autonomous Region was better. The arils significantly inhibited seed germination, the germination of large seeds was better, and seedling growth from medium seeds was superior. H. hainanensis seeds were sensitive to dehydration, and intolerant to drought and low temperature, which is typical of recalcitrant seeds. The seeds are suitable for germination on a moist substrate surface with good water retention and breathability at 30-35℃.

Association between the geriatric nutritional risk index and clinical outcomes among peritoneal dialysis patients: A meta-analysis.

BACKGROUND: To identify the relationship between the geriatric nutritional risk index (GNRI) and clinical outcomes in patients receiving peritoneal dialysis (PD). METHODS: The PubMed, EBASE, Web of Science and CNKI databases were searched for available studies up to December 25, 2023. The primary outcome was all-cause mortality, and the secondary outcomes included the incidence of PD dropout, major adverse cardiac and cerebrovascular events (MACCEs), technique failure and peritonitis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were combined to evaluate the predictive value of the GNRI for the occurrence of the above endpoints. RESULTS: Ten cohort studies with 3897 patients were included. The pooled results demonstrated that a lower GNRI was significantly associated with a greater incidence of all-cause mortality (HR = 0.71, 95% CI: 0.55-0.91; P = .007). In addition, a decreased GNRI predicted the occurrence of dropout from PD (HR = 0.971, 95% CI: 0.945-0.998, P = .034) and MACCE (HR = 0.95, 95% CI: 0.92-0.98, P = .001). However, no significant associations of the GNRI with technique failure (P = .167) or peritonitis (P = .96) were observed. CONCLUSION: A low GNRI is significantly associated with poor clinical outcomes and might serve as a novel and valuable prognostic indicator among PD patients.

Iodine-induced synthetic method and pharmacokinetic study of cis- and trans-crocetin.

Objective: This experiment aimed to obtain the relatively rare cis-crocetin isomer from natural plants, which predominantly exist in the more stable all-trans configuration. This was achieved through iodine-induced isomerization, followed by purification and structural identification. The study also aimed to compare the pharmacokinetic differences between cis- and trans-crocetin in vivo. Methods: Trans-crocetin of high purity was extracted by hydrolysis from gardenia yellow pigment. Cis-crocetin was then synthesized through an optimized electrophilic addition reaction induced by elemental iodine, and subsequently separated and purified via silica gel column chromatography. Structural identification of cis-crocetin was determined using IR, UV, and NMR techniques. In vivo pharmacokinetic studies were conducted for both cis- and trans-crocetin. In addition to this, we have conducted a comparative study on the in vivo anti-hypoxic activity of trans- and cis-crocetin. Results: Under the selected reaction conditions using DMF as the solvent, with a concentration of 2.5 mg/mL for both trans-crocetin and the iodine solution, and adjusting the illumination time according to the amount of trans-crocetin, the rate of iodine-induced isomerization was the fastest. Cis-crocetin was successfully obtained and, after purification, its structure was identified and found to be consistent with reported data. Cis-crocetin exhibited a faster absorption rate and higher bioavailability, and despite its shorter half-life, it could partially convert to trans-crocetin in the body, thereby extending the duration of the drug's action within the body to some extent. Conclusion: This study accomplished the successful preparation and structural identification of cis-crocetin. Additionally, through pharmacokinetic studies, it uncovered notable variations in bioavailability between cis- and trans-crocetin. These findings serve as a solid scientific foundation for future functional research and practical applications in this field.

Impaired Relaxation in Induced Pluripotent Stem Cell-Derived Cardiomyocytes with Pathogenic TNNI3 Mutation of Pediatric Restrictive Cardiomyopathy.

BACKGROUND: Restrictive cardiomyopathy (RCM) is characterized by impaired diastolic function with preserved ventricular contraction. Several pathogenic variants in sarcomere genes, including TNNI3, are reported to cause Ca2+ hypersensitivity in cardiomyocytes in overexpression models; however, the pathophysiology of induced pluripotent stem cell (iPSC)-derived cardiomyocytes specific to a patient with RCM remains unknown. METHODS AND RESULTS: We established an iPSC line from a pediatric patient with RCM and a heterozygous TNNI3 missense variant, c.508C>T (p.Arg170Trp; R170W). We conducted genome editing via CRISPR/Cas9 technology to establish an isogenic correction line harboring wild type TNNI3 as well as a homozygous TNNI3-R170W. iPSCs were then differentiated to cardiomyocytes to compare their cellular physiological, structural, and transcriptomic features. Cardiomyocytes differentiated from heterozygous and homozygous TNNI3-R170W iPSC lines demonstrated impaired diastolic function in cell motion analyses as compared with that in cardiomyocytes derived from isogenic-corrected iPSCs and 3 independent healthy iPSC lines. The intracellular Ca2+ oscillation and immunocytochemistry of troponin I were not significantly affected in RCM-cardiomyocytes with either heterozygous or homozygous TNNI3-R170W. Electron microscopy showed that the myofibril and mitochondrial structures appeared to be unaffected. RNA sequencing revealed that pathways associated with cardiac muscle development and contraction, extracellular matrix-receptor interaction, and transforming growth factor-ß were altered in RCM-iPSC-derived cardiomyocytes. CONCLUSIONS: Patient-specific iPSC-derived cardiomyocytes could effectively represent the diastolic dysfunction of RCM. Myofibril structures including troponin I remained unaffected in the monolayer culture system, although gene expression profiles associated with cardiac muscle functions were altered.

Polyethylene Glycol Priming Enhances the Seed Germination and Seedling Growth of Scutellaria baicalensis Georgi under Salt Stress.

Seed priming has become a practical pre-sowing strategy to deal with abiotic stresses. This study aims to explore the effects of polyethylene glycol (PEG) priming on seed germination and seedling growth of Scutellaria baicalensis Georgi under salt stress. Regardless of seed priming, salt stress significantly inhibited the seed germination and seedling growth of S. baicalensis. PEG priming significantly alleviates the inhibitory effects of salt stress on seed germination and seedling growth when compared to non-priming and water priming. Among all treatments, PEG priming exhibited the highest germination rate, germination potential, seed vigor index, fresh weight, dry weight, and plant length; the highest contents of proline, soluble sugar, and soluble protein; the highest K+/Na+ ratio and relative water content; the highest antioxidant activities and contents; but the lowest H2O2, malondialdehyde (MDA) content, and relative electrical conductivity in response to salt stress. In addition, PEG priming had the highest transcript levels of antioxidant-related genes among all treatments under NaCl stress. Taken together, the results demonstrated that seed priming with PEG could be recommended as an effective practice to enhance the germination and early seedling growth of S. baicalensis under saline conditions.

Geniposide from Gardeniae Fructus exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The desiccative ripe fruits of Gardenia (Gardenia jasminoides Ellis) (called Zhizi in China) are known with cold character and the effects of reducing fire except vexed, clearing away heat evil, and cooling blood and eliminating stasis. Zhizi is often clinical formulated to treat various types of fever. Fever is a sign of inflammation and, geniposide from Zhizi has been proved with anti-inflammatory in various inflammatory models. AIM OF STUDY: The aim of this study was to investigate the antipyretic role of geniposide with three classical inflammatory fever models and explore the underlying mechanisms. MATERIALS AND METHODS: Water extract (WE), high polar part (HP), iridoid glycoside part (IG), and gardenia yellow pigment part (GYP) from Gardeniae Fructus (GF) were obtained from Zhizi. The antipyretic activities of these composes were tested with dry yeast induced fever rats. Geniposide was further purified from IG and the antipyretic activity was evaluated by gavage, intraperitoneal injection, and caudal intravenous injection to rats of fever induced by dry yeast, lipopolysaccharide (LPS), and 2, 4-dinitrophenol (DNP) in rats. Then, the mechanism of geniposide by intragastric administration was studied. The contents of thermoregulatory mediators and inflammatory factors relating to TLR4/NF-κB pathway in serum were determined by ELISA and Western blot, and the pathological changes of the hypothalamus were observed by HE staining. RESULTS: The temperature was decreased by geniposide in the three fever model rats. Geniposide can not only inhibit the increase of inflammatory factors in serum but also protect the hypothalamus from fever pathological damage in the three fever models. Western blot showed that geniposide could inhibit the TLR4/NF-κB pathway. CONCLUSION: Geniposide exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

A Promising New Model: Establishment of Patient-Derived Organoid Models Covering HPV-Related Cervical Pre-Cancerous Lesions and Their Cancers.

The lack of human-derived in vitro models that recapitulate cervical pre-cancerous lesions has been the bottleneck in researching human papillomavirus (HPV) infection-associated pre-cancerous lesions and cancers for a long time. Here, a long-term 3D organoid culture protocol for high-grade squamous intraepithelial lesions and cervical squamous cell carcinoma that stably recapitulates the two tissues of origin is described. Originating from human-derived samples, a small biobank of cervical pre-tumoroids and tumoroids that faithfully retains genomic and transcriptomic characteristics as well as the causative HPV genome is established. Cervical pre-tumoroids and tumoroids show differential responses to common chemotherapeutic agents and grow differently as xenografts in mice. By coculture organoid models with peripheral blood immune cells (PBMCs) stimulated by HPV antigenic peptides, it is illustrated that both organoid models respond differently to immunized PBMCs, supporting organoids as reliable and powerful tools for studying virus-specific T-cell responses and screening therapeutic HPV vaccines. In this study, a model of cervical pre-cancerous lesions containing HPV is established for the first time, overcoming the bottleneck of the current model of human cervical pre-cancerous lesions. This study establishes an experimental platform and biobanks for in vitro mechanistic research, therapeutic vaccine screening, and personalized treatment for HPV-related cervical diseases.

High-contrast multicolour photoswitching based on dithienylethene Schiff base with a hydrazinylquinoline moiety.

A new asymmetrical photochromic diarylethene DTE-HQo composed of a 2-hydrazinoquinoline moiety as the binding unit for ions and dithenylethene as a photoswitching trigger was reported. DTE-HQo displayed favourable photochromism upon irradiation with UV/vis light. Its fluorescent behaviour could be efficiently modulated by light, Zn2+, Cd2+ and HSO4-. The binding of Zn2+ induced a strong fluorescence peak at 510 nm in DTE-HQo due to the formation of a 1:2 complex [Zn2+ + 2DTE-HQo], resulting in a notable colour change from dark to intense white emission. Triggered by Cd2+, DTE-HQo formed a 1:1 complex [Cd2+ + DTE-HQo], leading to an enhanced emission intensity by 21-fold with an emission peak red-shifted from 461 nm to 514 nm. Unexpectedly, [Zn2+ + 2DTE-HQo] underwent hydrolysis when stimulated with water, generating a yellow-emitting complex [Zn2+ + DTE-HQo]. This color change easily distinguishes it from Cd2+ complex. Additionally, DTE-HQo showed high selectivity towards HSO4- and exhibited distinct "turn-on" fluorescence with a colour change from dark to bright blue upon stimulation. Moreover, the strong emission complexes of DTE-HQo with Zn2+, Cd2+ and HSO4- could be effectively quenched during the photocyclization process. Therefore, DTE-HQo can serve as an unimolecular multicolour photoswitching chemosensor, offering potential applications as a multifunctional probe for detecting Zn2+, Cd2+ and HSO4-.

Stem cells implanted with nanofibrous mats for injured endometrial regeneration and immune-microenvironment remodeling.

Severe endometrial injury caused by invasive uterine operation and/or endometritis often results in intrauterine adhesions (IUAs), which are named Asherman's syndrome (AS), further leading to menstrual disorders, infertility and severe complications during pregnancy and delivery. IUAs or AS has been a challenging medical problem. Stem cells are a promising therapeutic modality for endometrial regeneration in patients with refractory AS. Here, we developed a new system of adipose-derived mesenchymal stem cells (ADMSCs) implantation on silk fibroin/polycaprolactone (SF/PCL) electrospun nanofibers (ADMSCs-SF/PCL) and used it in the damaged endometrium of a rat model. After SF/PCL enhanced the proliferation of transplanted ADMSCs, the results showed that the ADMSCs-SF/PCL system could recover morphology, promote regeneration of the glands and angiogenesis by increasing CD31 expression, and reverse endometrial fibrosis by decreasing TGF-ß/Smad expression. In addition, the ADMSCs-SF/PCL system also increased the expression of differentiation and decidualization markers, including HOXA11, HAND2 and FOXO1. Most importantly, the ADMSCs-SF/PCL system could remodel the special immune microenvironment, resulting in dominant NK infiltration and a normal Th1/Th2 bias in the endometrium. Moreover, this treatment had a lower but more persistent effect than estrogen. Thus, the ADMSCs-SF/PCL system enhanced endometrial restoration, suggesting a promising strategy for damaged endometrial regeneration and immune microenvironment remodeling.

Effect of different hypoxic and hypobaric interventions on blood gas and erythrocyte-related indicators in rats. / ä¸åŒç¼ºæ°§å¹²é¢„å¯¹ä½ŽåŽ‹ä½Žæ°§æ¨¡åž‹é¼ è¡€æ°”åŠçº¢ç»†èƒžç›¸å ³æŒ‡æ ‡çš„å½±å“.

OBJECTIVES: To explore the effects of hypoxic and hypobaric conditions on blood gas and erythrocyte-related indicators in rats. METHODS: SD male rats were exposed to low-pressure hypoxic conditions simulating an altitude of 6500 m in a small or a large experimental cabin. Abdominal aortic blood samples were collected and blood gas indicators, red blood cells (RBCs) count, and hemoglobin (Hb) content were measured. The effects of exposure to different hypoxia times, different hypoxia modes, normal oxygen recovery after hypoxia, and re-hypoxia after hypoxia preconditioning on blood gas indicators, RBCs count and Hb content were investigated. RESULTS: The effect of blood gas indicators was correlated with the length of exposure time of hypoxia and the reoxygenation after leaving the cabin. Hypoxia caused acid-base imbalance and its severity was associated with the duration of hypoxia; hypoxia also led to an increase in RBCs count and Hb content, and the increase was also related to the time exposed to hypoxia. The effects of reoxygenation on acid-base imbalance in rats caged in a small animal cabin were more severe that those in a large experimental cabin. Acetazolamide alleviated the effects of reoxygenation after leaving the cabin. Different hypoxia modes and administration of acetazolamide had little effect on RBCs count and Hb content. Normal oxygen recovery can alleviate the reoxygenation and acid-base imbalance of hypoxic rats after leaving the cabin and improve the increase in red blood cell and hemoglobin content caused by hypoxia. The improvement of hypoxia preconditioning on post hypoxia reoxygenation is not significant, but it can alleviate the acid-base imbalance caused by hypoxia in rats and to some extent improve the increase in red blood cell and hemoglobin content caused by hypoxia. CONCLUSIONS: Due to excessive ventilation and elevated RBCs count and Hb content after hypoxia reoxygenation, oxygen partial pressure and other oxygenation indicators in hypoxic rats are prone to become abnormal, while blood gas acid-base balance indicators are relatively stable, which are more suitable for evaluating the degree of hypoxia injury and related pharmacological effects in rats.

LncBIRC3-OT promotes the malignant progression of glioma by interacting with RELA to upregulate stanniocalcin-1 expression.

Glioma is the most common malignant intracranial tumor, accounting for 80 % of all malignant brain tumors. Growing evidence suggests that lncRNAs are involved in the growth, angiogenesis, metastasis, and therapeutic resistance in a variety of tumors, including glioma. In this study, lncBIRC3-OT (NONHSAT159592.1), which is highly expressed in glioma, was screened by RNA-seq method and verified by quantitative reverse transcription polymerase chain reaction. Subsequently, we knocked down the endogenous expression of lncBIRC3-OT in U87 and U251 cells and found that down-regulated lncBIRC3-OT inhibited cell proliferation, colony formation, migration, and invasion. Mechanically, lncBIRC3-OT could guide RELA protein to the stanniocalcin-1 (STC1) promoter, initiate STC1 transcription, and ultimately promote the progression of glioma. Together, these findings suggest that lncBIRC3-OT is an important regulator promoting glioma progression, and may be a promising therapeutic target for glioma.

Isogenic pairs of induced-pluripotent stem-derived endothelial cells identify DYRK1A/PPARG/EGR1 pathway is responsible for Down syndrome-associated pulmonary hypertension.

Down syndrome (DS) is the most prevalent chromosomal disorder associated with a higher incidence of pulmonary arterial hypertension (PAH). The dysfunction of vascular endothelial cells (ECs) is known to cause pulmonary arterial remodeling in PAH, although the physiological characteristics of ECs harboring trisomy 21 (T21) are still unknown. In this study, we analyzed the human vascular ECs by utilizing the isogenic pairs of T21-induced pluripotent stem cells (iPSCs) and corrected disomy 21 (cDi21)-iPSCs. In T21-iPSC-derived ECs, apoptosis and mitochondrial reactive oxygen species (mROS) were significantly increased, and angiogenesis and oxygen consumption rate (OCR) were significantly impaired as compared with cDi21-iPSC-derived ECs. The RNA-sequencing identified that EGR1 on chromosome 5 was significantly upregulated in T21-ECs. Both EGR1 suppression by siRNA and pharmacological inhibitor could recover the apoptosis, mROS, angiogenesis, and OCR in T21-ECs. Alternately, the study also revealed that DYRK1A was responsible to increase EGR1 expression via PPARG suppression, and that chemical inhibition of DYRK1A could restore the apoptosis, mROS, angiogenesis, and OCR in T21-ECs. Finally, we demonstrated that EGR1 was significantly upregulated in the pulmonary arterial ECs from lung specimens of a patient with DS and PAH. In conclusion, DYRK1A/PPARG/EGR1 pathway could play a central role for the pulmonary EC functions and thus be associated with the pathogenesis of PAH in DS.