A through-space charge transfer pyrene-based fluorophore with anti-quenching behavior for deep-blue organic light-emitting devices.

A through-space charge transfer pyrene-based fluorophore has been developed for organic light-emitting devices (OLEDs). This material exhibits deep-blue fluorescence, bipolar characteristics, and anti-quenching behavior in the solid state. It proves to be an effective emitter for both doped and nondoped deep-blue OLEDs.

Effect of mPEG-PLGA on Drug Crystallinity and Release of Long-Acting Injection Microspheres: In Vitro and In Vivo Perspectives.

PURPOSE: Traditional progesterone (PRG) injections require long-term administration, leading to poor patient compliance. The emergence of long-acting injectable microspheres extends the release period to several days or even months. However, these microspheres often face challenges such as burst release and incomplete drug release. This study aims to regulate drug release by altering the crystallinity of the drug during the release process from the microspheres. METHODS: This research incorporates methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide) (mPEG-PLGA) into poly(lactide-co-glycolide) (PLGA) microspheres to enhance their hydrophilicity, thus regulating the release rate and drug morphology during release. This modification aims to address the issues of burst and incomplete release in traditional PLGA microspheres. PRG was used as the model drug. PRG/mPEG-PLGA/PLGA microspheres (PmPPMs) were prepared via an emulsification-solvent evaporation method. Scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC) were employed to investigate the presence of PRG in PmPPMs and its physical state changes during release. RESULTS: The addition of mPEG-PLGA altered the crystallinity of the drug within the microspheres at different release stages. The crystallinity correlated positively with the amount of mPEG-PLGA incorporated; the greater the amount, the faster the drug release from the formulation. The bioavailability and muscular irritation of the long-acting injectable were assessed through pharmacokinetic and muscle irritation studies in Sprague-Dawley (SD) rats. The results indicated that PmPPMs containing mPEG-PLGA achieved low burst release and sustained release over 7 days, with minimal irritation and self-healing within this period. PmPPMs with 5% mPEG-PLGA showed a relative bioavailability (Frel) of 146.88%. IN CONCLUSION: In summary, adding an appropriate amount of mPEG to PLGA microspheres can alter the drug release process and enhance bioavailability.

Current therapy in amyotrophic lateral sclerosis (ALS): A review on past and future therapeutic strategies.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the first and second motoneurons (MNs), associated with muscle weakness, paralysis and finally death. The exact etiology of the disease still remains unclear. Currently, efforts to develop novel ALS treatments which target specific pathomechanisms are being studied. The mechanisms of ALS pathogenesis involve multiple factors, such as protein aggregation, glutamate excitotoxicity, oxidative stress, mitochondrial dysfunction, apoptosis, inflammation etc. Unfortunately, to date, there are only two FDA-approved drugs for ALS, riluzole and edavarone, without curative treatment for ALS. Herein, we give an overview of the many pathways and review the recent discovery and preclinical characterization of neuroprotective compounds. Meanwhile, drug combination and other therapeutic approaches are also reviewed. In the last part, we analyze the reasons of clinical failure and propose perspective on the treatment of ALS in the future.

Triazoles in Medicinal Chemistry: Physicochemical Properties, Bioisosterism, and Application.

Triazole demonstrates distinctive physicochemical properties, characterized by weak basicity, various dipole moments, and significant dual hydrogen bond acceptor and donor capabilities. These features are poised to play a pivotal role in drug-target interactions. The inherent polarity of triazole contributes to its lower logP, suggesting the potential improvement in water solubility. The metabolic stability of triazole adds additional value to drug discovery. Moreover, the metal-binding capacity of the nitrogen atom lone pair electrons of triazole has broad applications in the development of metal chelators and antifungal agents. This Perspective aims to underscore the unique physicochemical attributes of triazole and its application. A comparative analysis involving triazole isomers and other heterocycles provides guiding insights for the subsequent design of triazoles, with the hope of offering valuable considerations for designing other heterocycles in medicinal chemistry.

Severe hyponatremia and diabetes insipidus caused by low-dose cyclophosphamide in breast cancer patients: A case report and literature review.

RATIONALE: Cyclophosphamide (CTX) is widely used in the treatment of malignancies and autoimmune diseases. Although severe hyponatremia caused by low-dose CTX chemotherapy is uncommon, it can lead to serious complications and even death. PATIENT CONCERNS: A 44-year-old woman with left-sided breast cancer suddenly experienced headaches, disorientation and weakness after receiving low-dose neoadjuvant chemotherapy combined with CTX and doxorubicin. DIAGNOSES: The patient pathology showed invasive breast carcinoma. She developed severe hyponatremia and a generalized seizure after completing the first cycle of neoadjuvant chemotherapy with CTX and doxorubicin. Laboratory tests showed a serum sodium of 118 mmol/L (normal range 135-145 mmol/L) and potassium sodium 3.16 mmol/L (normal range 3.5-5.5 mmol/L). Subsequently, the patient developed secondary diabetes insipidus 4 hours after sodium supplementation, her 24-hour urine volume was 4730 mL (normal range 1000-2000 mL/24 hours), and the urine specific gravity decreased to 1.005. INTERVENTIONS: The patient was given intravenous sodium chloride (500 mL of 3%NaCl, 100 mL/hour) and potassium chloride (500 mL of 0.3%KCl, 250 mL/hour). Meanwhile, she was advised to reduce her water intake, and pituitrin was administered to prevent dehydration caused by diabetes insipidus. OUTCOMES: The patient completely recovered after correcting of the serum sodium concentration (137 mmol/L) without any neurological deficits. After discontinuing pituitrin, her 24-hour urine volume was 2060 mL and the urine specific gravity was 1.015. LESSONS: This is a typical case of severe hyponatremia induced by low-dose CTX. Clinicians and healthcare providers should be aware of this potential toxicity, and appropriate monitoring should be implemented.

Pharmacokinetics and molecular docking of the cardioprotective flavonoids in Dalbergia odorifera.

The purpose of this research was to investigate the cardioprotective effects and pharmacokinetics of Dalbergia odorifera flavonoids. The cardioprotective effects were detected by hematoxylin-eosin staining histopathological observations and the detection of myocardial enzymes by kits in serum, peroxidation and antioxidant levels and ATPase activities by kits in the homogenate supernatant, and antioxidant and apoptosis-related protein expression in heart tissue by immunohistochemistry. The pharmacokinetics parameters of the flavonoids in rat plasma were investigated by ultra-high-performance liquid chromatography coupled with tandem mass spectrometry. Molecular docking of the compounds absorbed by the blood with specific proteins was carried out. D. odorifera flavonoids significantly reduced the levels of creatinine kinase, alanine transaminase, nitric oxide, and Hydrogen peroxide, elevated the levels of glutathione, superoxide dismutase, and ATPase, significantly reduced the pathological degree of heart tissue and had obvious anti-myocardial ischemia efficacy. Nine out of the 17 flavonoids were detected in rat plasma. The peak concentration and the area under the plasma concentration-time curve values of 3'-O-methylviolanone and sativanone were significantly higher than those of other ingredients. The peak time of most flavonoids (except for Genistein and Pruneion) was lower than 2 h, while the half-life of elimination of the nine flavonoids ranged from 3.32 to 21.5 h. The molecular docking results showed that daidzein, dalbergin, formononetin, and genistein had the potential to bind to the target proteins. The results of the study provide an important basis for understanding the cardioprotective effects and clinical application of D. odorifera.

Regional lymph node density-based nomogram predicts prognosis in nasopharyngeal carcinoma patients without distant metastases.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a relatively common type of cancer in Southern China, with local recurrence or distant metastases even after radical treatment; consequently, it is critical to identify the patients at higher risk for these events beforehand. This study aimed to assess the prognostic value of regional lymph node density (RLND) associated nomograms in NPC and to evaluate the utility of nomograms in risk stratification. METHODS: A total of 610 NPC patients without distant metastases (425 in the training and 185 in the validation cohort) were enrolled. The MRI-identified nodal features and clinical characteristics were documented, and the RLND was calculated. Cox analyses were conducted to identify prognostic-associated factors. Nomograms were generated based on the multivariate analysis results. The predictive accuracy and discriminative ability of the nomogram models were determined using the concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration curve; the results were compared with those of the tumor-node-metastasis (TNM) classification. Decision curve analysis (DCA) and C-index were used to assess the prognostic effect and added discriminative ability of RLND. We also estimated the optimal RLND-based nomogram score cut-off values for survival prediction. RESULTS: RLND was an independent predictor of overall survival (OS) and disease-free survival (DFS), with hazard ratios of 1.36 and 1.30, respectively. RLND was utilized in the construction of nomograms, alongside other independent prognostic factors. The RLND-based nomogram models presented a more effective discriminative ability than the TNM classification for predicting OS (C-index, 0.711 vs. 0.680) and DFS (C-index, 0.681 vs. 0.669), with favorable calibration and consistency. The comparison of C-index values between the nomogram models with and without RLND provided substantiation of the crucial role RLND plays in these models. DCA confirmed the satisfactory clinical practicability of RLND. Moreover, the nomograms were used to categorize the patients into three groups (high-, middle-, and low-risk), and the Kaplan-Meier curves showed significant differences in prognosis between them (p < 0.05). These results were verified in the validation cohort. CONCLUSION: RLND stands as a robust prognostic factor in NPC. The RLND-based nomograms excel in predicting survival, surpassing the TNM classification.

Inhibition of Son of Sevenless Homologue 1 (SOS1): Promising therapeutic treatment for KRAS-mutant cancers.

Kristen rat sarcoma (KRAS) is one of the most common oncogenes in human cancers. As a guanine nucleotide exchange factor, Son of Sevenless Homologue 1 (SOS1) represents a potential therapeutic concept for the treatment of KRAS-mutant cancers because of its activation on KRAS and downstream signaling pathways. In this review, we provide a comprehensive overview of the structure, biological function, and regulation of SOS1. We also focus on the recent advances in SOS1 inhibitors and emphasize their binding modes, structure-activity relationships and pharmacological activities. We hope that this publication can provide a comprehensive compendium on the rational design of SOS1 inhibitors.

Agarwood extract mitigates alcoholic fatty liver in C57 mice via anti­oxidation and anti­inflammation.

Alcoholic fatty liver disease (AFLD) is a disease with a high incidence rate among individuals who drink alcohol. Our previous study found that agarwood alcohol extracts (AAEs) have a protective effect against drug­induced liver damage via anti­inflammatory and antioxidant mechanisms. Therefore, we hypothesized that agarwood may have a protective effect against AFLD. The present study assessed the potential protective effects and the underlying mechanism of action of AAEs for the treatment of an AFL in vivo model. The AFLD mouse model was established by continuous high fat diet and alcohol gavage in C57 mice. After treatment with AAEs, blood was collected, liver and adipose tissues were removed and liver and adipose indexes were analyzed. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG) and cholesterol (CHO) in serum were detected. The liver tissue was assessed using pathological sections. Biochemical methods were used to detect the levels of oxidative stress in the supernatant of liver tissue homogenate. The levels of pro­inflammatory cytokines in the serum were detected by ELISA. The protein expression levels of nuclear erythroid 2­related factor 2 (Nrf2) and nuclear factor kappa­B (NF­κB) in liver tissues were detected using western blotting. AAE treatment decreased the liver and adipose indexes, reduced the levels of AST, ALT, TG and CHO, improved the liver pathological characteristics and enhanced antioxidant and anti­inflammatory activities. In addition, AAEs increased the protein expression level of Nrf2 and decreased the protein expression level of NF­κB compared with AFL mice. AAE­treated animals exhibited reduced metabolic enzyme and blood lipid levels, demonstrated improved liver function and relieved the pathological damage of AFLD induced by consuming a high fat and alcohol diet. AAEs have potential protective effects in AFLD via antioxidant and anti­inflammatory mechanisms.

[Anxiolytic and antidepressant effects of agarwood inhalation and its mechanism].

This study used m-chloropheniperazine(MCPP) and chronic unforeseeable mild stress(CUMS) to induce the rat models of anxiety and depression, respectively. The behaviors of rats were observed by the open field test(OFT), light-dark exploration test(LDE), tail suspension test(TST), and forced swimming test(FST), and the antidepressant and anxiolytic effects of agarwood essential oil(AEO), agarwood fragrant powder(AFP), and agarwood line incense(ALI) were explored. The enzyme-linked immunosorbent assay(ELISA) was used to determine the levels of 5-hydroxytryptamine(5-HT), glutamic acid(Glu), and γ-aminobutyric acid(GABA_A) in the hippocampal area. The Western blot assay was used to determine the protein expression levels of glutamate receptor 1(GluR1) and vesicular glutamate transporter type 1(VGluT1), exploring the anxiolytic and antidepressant mechanism of agarwood inhalation. The results showed that compared with the anxiety model group, the AEO, AFP, and ALI groups decreased the total distance(P<0.05), decreased the velocity of movements(P<0.05), prolonged the immobile time(P<0.05), and reduced the distance and velocity of the rat model of anxiety in the dark box(P<0.05). Compared with the depression model group, the AEO, AFP, and ALI groups increased the total distance and average velocity(P<0.05), reduced the immobile time(P<0.05), and reduced the forced swimming and tail suspension time(P<0.05). In terms of transmitter regulation, the AEO, AFP, and ALI groups decreased the level of Glu in the rat model of anxiety(P<0.05) and increased the levels of GABA_A and 5-HT(P<0.05), while the AEO, AFP, and ALI groups all increased the level of 5-HT in the rat model of depression(P<0.05) and decreased the levels of GABA_A and Glu(P<0.05). At the same time, the AEO, AFP, and ALI groups all increased the protein expression levels of GluR1 and VGluT1 in the hippocampus of the rat models of anxiety and depression(P<0.05). In conclusion, AEO, AFP, and ALI exert anxiolytic and antidepressant effects, and the mechanism might be related to the regulation of the neurotransmitter and the protein expression of GluR1 and VGluT1 in the hippocampus.

Agarwood essential oil inhalation exerts antianxiety and antidepressant effects via the regulation of Glu/GABA system homeostasis.

Depression and anxiety are common diseases that endanger the physical and mental health of individuals. Agarwood incense inhalation has been used as a traditional Chinese medicine for relaxation and to improve sleep for centuries. In a previous study by the authors it was demonstrated that agarwood essential oil (AEO) injection exerted anxiolytic and antidepressant effects. Therefore the present study further investigated the anxiolytic and antidepressant effects of AEO inhalation on anxiolytic mice induced by M-chlorophenylpiperazine and depressive mice induced by chronic unpredictable mild stress. The results demonstrated that AEO exerted a significant anxiolytic effect, whereby autonomous movements were inhibited during the light dark exploration test and open field test. Furthermore, the tail suspension test and the forced swimming test demonstrated that AEO also exerted an antidepressant effect, whereby the immobility times were decreased. Moreover, AEO was determined to increase the levels of 5-hydroxytryptamine, γ-aminobutyric acid (GABA) A receptor (GABAA) and glutamate (Glu) in anxiolytic mice and inhibit the levels of GABAA and Glu in depressive mice. Further investigations into how AEO affected the Glu/GABA system demonstrated that AEO markedly increased the protein expression levels of GABA transaminase (GABAT), glutamate metabotropic receptor 5 (GRM5), glutamate ionotropic receptor AMPA type subunit 1 (GluR1) and vesicular glutamate transporter 1 (VGluT1). Furthermore, AEO reduced the expression levels of GABAT, glutamate ionotropic receptor NMDA type subunit 2B and GRM5, and enhanced the expression levels of GluR1 and VGluT1. These results demonstrated that AEO potentially possesses antianxiety and antidepressant properties. The present study determined that the mechanism was related to the regulation of Glu/GABA neurotransmitter system homeostasis.

Characterization of femtosecond laser-induced grating scattering of a continuous-wave laser light in air.

Nanosecond laser-induced grating scattering/spectroscopy (LIGS) technique has been widely applied for measuring thermodynamic parameters such as temperature and pressure in gaseous and liquid media. Recently, femtosecond (fs) laser was demonstrated to induce the grating and develop the fs-LIGS technique for gas thermometry. In this work, we systematically investigated the fs-LIGS signal generation using 35 fs, 800 nm laser pulses at 1 kHz repetition rate in ambient air by varying the pump laser energies, the probe laser powers and the temporal delays between two pump laser pulses. The stability of single-shot fs-LIGS signal was studied, from which we observed that the signal intensity exhibits a significant fluctuation while the oscillation frequency shows a much better stability. A 4.5% precision of the oscillation frequency was achieved over 100 single-shot signals. By using a previously-developed empirical model, the fs-LIGS signals were fitted using nonlinear least-squares fitting method, by which crucial time constants characterizing the signal decay process were extracted and their dependences on the pump laser energy were studied. From the measured results and theoretical analysis, we found that the appropriate range of the overall pump laser energy for reliable fs-LIGS measurements is approximately located within 80 ∼ 300 µJ. The limitations on the accuracy and precision of the fs-LIGS measurements, the origin of destructive influence of plasma generation on the signal generation as well as the electrostriction contribution were also discussed. Our investigations could contribute to a better understanding of the fs-LIGS process and further applications of the technique in single-shot gas thermometry and pressure measurements in various harsh conditions.

Cefazolin/BMP-2-Loaded Mesoporous Silica Nanoparticles for the Repair of Open Fractures with Bone Defects.

The study aimed to explore the feasibility of a nanodrug delivery system to treat open fractures with bone defects. We developed a cefazolin (Cef)/bone morphogenetic protein 2 (BMP-2)@mesoporous silica nanoparticle (MSN) delivery system; meanwhile, Cef/MBP-2@ poly(lactic-co-glycolic acid) (PLGA) was also developed as control. For the purpose of determining the osteogenic and anti-inflammatory actions of the nanodelivery system, we cultured bone marrow mesenchymal stem cells (BMSCs) and constructed a bone defect mouse model to evaluate its clinical efficacy. After physicochemical property testing, we determined that MSN had good stability and did not easily accumulate or precipitate and it could effectively prolong the Cef's half-life by nearly eight times. In BMSCs, we found that compared with the PLGA delivery system, MSNs better penetrated into the bone tissue, thus effectively increasing BMSCs' proliferation and migration ability to facilitate bone defect repair. Furthermore, the MSN delivery system could improve BMSCs' mineralization indexes (alkaline phosphatase [ALP], osteocalcin [OCN], and collagen I [Col I]) to effectively improve its osteogenic ability. Moreover, the MSN delivery system could inhibit inflammation in bone defect mice, which was mainly reflected in its ability to reduce the release of IL-1ß and IL-4 and increase IL-10 levels; it could also effectively reduce apoptosis of CD4+ and CD8+ T cells, thus improving their immune function. Furthermore, the percentage of new bones, bone mineral density, trabecular volume, and trabecular numbers in the fracture region were improved in mice treated with MSN, which allowed better repair of bone defects. Hence, Cef/BMP-2@MSN may be feasible for open fractures with bone defects.

3D bioprinting of in situ vascularized tissue engineered bone for repairing large segmental bone defects.

Large bone defects remain an unsolved clinical challenge because of the lack of effective vascularization in newly formed bone tissue. 3D bioprinting is a fabrication technology with the potential to create vascularized bone grafts with biological activity for repairing bone defects. In this study, vascular endothelial cells laden with thermosensitive bio-ink were bioprinted in situ on the inner surfaces of interconnected tubular channels of bone mesenchymal stem cell-laden 3D-bioprinted scaffolds. Endothelial cells exhibited a more uniform distribution and greater seeding efficiency throughout the channels. In vitro, the in situ bioprinted endothelial cells can form a vascular network through proliferation and migration. The in situ vascularized tissue-engineered bone also resulted in a coupling effect between angiogenesis and osteogenesis. Moreover, RNA sequencing analysis revealed that the expression of genes related to osteogenesis and angiogenesis is upregulated in biological processes. The in vivo 3D-bioprinted in situ vascularized scaffolds exhibited excellent performance in promoting new bone formation in rat calvarial critical-sized defect models. Consequently, in situ vascularized tissue-engineered bones constructed using 3D bioprinting technology have a potential of being used as bone grafts for repairing large bone defects, with a possible clinical application in the future.

Effective Components and Molecular Mechanism of Agarwood Essential Oil Inhalation and the Sedative and Hypnotic Effects Based on GC-MS-Qtof and Molecular Docking.

Agarwood has been used for the administration of hypnotic therapy. Its aromatic scent induces a relaxed state. However, its aromatic constituents and the underlying molecular effect are still unclear. This study aims to determine the active substance and molecular mechanism of the hypnotic effect of agarwood essential oil (AEO) incense inhalation in insomniac mice. Insomnia models were induced by para-chlorophenylalanine (PCPA, 300 mg/kg) in mice. The sleep-promoting effect was evaluated. Neurotransmitter levels and its receptor were detected to explore the molecular mechanism. The effective components were analyzed by GC-Q/TOF-MS of AEO. The binding mechanisms of the core compounds and core targets were verified by molecular docking. These results showed that AEO inhalation could significantly shorten sleep latency and prolong sleep time, inhibit autonomous activity and exert good sedative and sleep-promoting effects. A mechanistic study showed that AEO inhalation increased the levels of γ-aminobutyric acid (GABAA), the GABAA/glutamic acid (Glu) ratio, 5-hydroxytryptamine (5-HT) and adenosine (AD), upregulated the expression levels of GluR1, VGluT1 and 5-HT1A and downregulated 5-HT2A levels. Component analysis showed that the most abundant medicinal compounds were eremophilanes, cadinanes and eudesmanes. Moreover, the docking results showed that the core components stably bind to various receptors. The study demonstrated the bioactive constituents and mechanisms of AEO in its sedative and hypnotic effects and its multicomponent, multitarget and multipathway treatment characteristics in PCPA-induced insomniac mice. These results provide theoretical evidence for insomnia treatment and pharmaceutical product development with AEO.

bFGF-Loaded Mesoporous Silica Nanoparticles Promote Bone Regeneration Through the Wnt/ß-Catenin Signalling Pathway.

Background: Bone defects remain an unsolved clinical problem due to the lack of effective osteogenic induction protocols. Nanomaterials play an important role in bone defect repair by stimulating osteogenesis. However, constructing an effective bioactive nanomaterial remains a substantial challenge. Methods: In this study, mesoporous silica nanoparticles (MSNs) were prepared and used as nanocarriers for basic fibroblast growth factor (bFGF). The characteristics and biological properties of the synthetic bFGF@MSNs were tested. The osteogenic effects of the particles on the behavior of MC3T3-E1 cells were investigated in vitro. In addition, the differentially expressed genes during induction of osteogenesis were analyzed by transcriptomic sequencing. Radiological and histological observations were carried out to determine bone regeneration capability in a distal femur defect model. Results: Achieving bFGF sustained release, bFGF@MSNs had uniform spherical morphology and good biocompatibility. In vitro osteogenesis induction experiments showed that bFGF@MSNs exhibited excellent osteogenesis performance, with upregulation of osteogenesis-related genes (RUNX2, OCN, Osterix, ALP). Transcriptomic sequencing revealed that the Wnt/ß-catenin signalling pathway could be activated in regulation of biological processes. In vivo, bone defect repair experiments showed enhanced bone regeneration, as indicated by radiological and histological analysis, after the application of bFGF@MSNs. Conclusion: bFGF@MSNs can promote bone regeneration by activating the Wnt/ß-catenin signalling pathway. These particles are expected to become a potential therapeutic bioactive material for clinical application in repairing bone defects in the future.

Gas-phase pressure measurement using femtosecond laser-induced grating scattering technique.

Gas-phase pressure measurements remain challenging in situations where local pressure rapidly changes or in hostile environments such as turbulent combustion. In this work, we demonstrate the implementation of the recently developed femtosecond laser-induced grating scattering (fs-LIGS) technique for pressure measurement in ambient air. With an overall femtosecond laser pulse energy of 185 µJ, fs-LIGS signals were generated for various gas pressure ranging from 0.2 to 3.0 bar. By theoretically fitting the signal and extracting the time constant of the stationary density modulation damping, the pressure is successfully derived. The derived values were compared to the gauge pressure, which shows a quasi-linear dependence with a slope of 0.96, suggesting the feasibility of the fs-LIGS technique for gas-phase pressure measurements.

Agarwood Alcohol Extract Protects against Gastric Ulcer by Inhibiting Oxidation and Inflammation.

BACKGROUND: Agarwood has been used for centuries, especially for treatment of gastrointestinal diseases. Earlier studies of our laboratory suggested that agarwood alcohol extracts (AAEs) provided gastric mucosal protection. This study aims to investigate the ameliorative effect of AAEs on ethanol-induced gastric ulcers and its mechanism. METHODS: Mice were given agarwood induced by the whole-tree agarwood-inducing technique alcohol extract (WTAAE, 0.71, 1.42, and 2.84 g/kg), wild agarwood induced by axe wounds alcohol extract (WAAE, 2.84 g/kg), and burning-chisel-drilling agarwood alcohol extract (FBAAE, 2.84 g/kg) orally, respectively. After 7 days' pretreatment with AAEs, the gastric ulcers were induced by absolute ethanol. The ulcer index, gastric histopathology, biochemical parameters, and inflammatory proteins were evaluated. RESULTS: Pharmacological results showed AAEs (1.42 and 2.84 g/kg) reduced the gastric occurrence and ulcer inhibition rates up to more than 60%. AAEs decreased the level of nitric oxide (NO) and increased glutathione (GSH) and superoxide dismutase (SOD) levels. Besides, AAEs decreased the levels of interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), but the interleukin-10 (IL-10) was upregulated. The expressions of nuclear factor kappa B (NF-κB) and phosphorylated protein 38 (p-P38) were inhibited. The effect of WTAAE was better than that of FBAAE and similar to that of WAAE at the dose of 2.84 g/kg. CONCLUSIONS: These results demonstrate that agarwood alleviates the occurrence and development of gastric ulcers via inhibiting oxidation and inflammation.

[Anti-asthmatic effect of agarwood alcohol extract in mice and its mechanism].

As recorded, agarwood has the function of improving qi reception and relieving asthma, but the underlying mechanism is unclear and rarely reported. Therefore, this study explored the anti-asthmatic effect of the alcohol extract of agarwood produced by the whole-tree agarwood-inducing technique(Agar-Wit) in the asthma mouse model induced by intraperitoneal injection of ovalbumin(OVA) + Al(OH)_3 combined with intranasal administration of OVA and the mechanism, and compared the anti-asthmatic effects of agarwood induced with different methods. Firstly, the anti-inflammatory and anti-asthmatic effects of Agar-Wit agarwood in mice were evaluated based on the asthma frequency, lung tissue injury, and peripheral inflammatory white blood cell(WBC) count and eosinophil count. Then, the levels of interleukin-1ß(IL-1ß), IL-17, and IL-10 in serum of mice were detected by enzyme-linked immunoassay(ELISA) and the expression of inflammation-and apoptosis-related genes in tissues was measured by reverse transcription polyme-rase chain reaction(RT-PCR) so as to preliminarily explore the anti-asthmatic mechanism. RESULTS:: showed that the alcohol extract of Agar-Wit agarwood significantly reduced asthma frequency, relieved pathological injury, improved peripheral WBC count and eosinophil count, decreased the levels of inflammatory cytokines IL-1ß and IL-17, elevated the level of anti-inflammatory cytokine IL-10, and down-regulated the mRNA expression of IL-1 R, tumor necrosis factor receptor R(TNFR), nuclear transcription factor-kappa B(NF-κB), Bax, and caspase 3, but had no significant influence on the expression of high-mobility group box 1(HMGB1) protein, caspase 8, and Bcl-2. The effect of Agar-Wit agarwood alcohol extract was better than that of wild agarwood alcohol extract and alcohol extract of agarwood induced with the burning-chisel-drilling method at the same dose. In conclusion, Agar-Wit agarwood can significantly alleviate inflammation and asthma, which is related to its anti-inflammation and anti-apoptosis activity.

Structural dynamics and vibrational feature of N-Acetyl-d-glucosamine in aqueous solution.

Molecular dynamics simulations and DFT calculations were performed for the demonstration of the structural dynamics and vibrational feature of N-Acetyl-d-glucosamine (NAG) in solution phase. The interactions between NAG and solvent molecules were evaluated through spatial distribution function and radial distribution function, and the preferred conformations of NAG in aqueous solution were revealed by cluster analysis. Results from normal mode analysis show that the solvent induced structural fluctuation of NAG could be reflected in the vibrational feature of specific chromophores, thus we can evaluate the molecular structure with the help of its vibrational signature based on the built correlation between molecular structure and vibrational frequencies of specific groups.