Botany, phytochemistry, pharmacology, and applications of Pandanus amaryllifolius Roxb.: A review.

Pandan (Pandanus amaryllifolius Roxb.), a member of the Pandanaceae family, has been consumed as food and medicine since ancient times. The current paper provides an overview of the botanical profile, phytochemistry, pharmacology, and applications of P. amaryllifolius. Information regarding P. amaryllifolius was collected from online sources (using PubMed, Science Direct, Google Scholar, Web of Science, ACS, and CNKI) as well as traditional textbooks. Over 100 compounds have been identified, including its characteristic components 2-Acetyl-1-pyrroline and Pandanus alkaloids. Several therapeutic uses of P. amaryllifolius, such as antioxidant, hypoglycemic, antimicrobial, and antitumor activities, have been demonstrated in modern pharmacological studies. Additionally, it could be applied in various fields, including food, energy, material, and the environment. Continued research on P. amaryllifolius can contribute to the development of new drugs and therapies for various diseases. And further studies are needed to improve its utilization.

Logic-Based Strategy for Spatiotemporal Release of Dual Extracellular Vesicles in Osteoarthritis Treatment.

To effectively treat osteoarthritis (OA), the existing inflammation must be reduced before the cartilage damage can be repaired; this cannot be achieved with a single type of extracellular vesicles (EVs). Here, a hydrogel complex with logic-gates function is proposed that can spatiotemporally controlled release two types of EVs: interleukin 10 (IL-10)+ EVs to promote M2 polarization of macrophage, and SRY-box transcription factor 9 (SOX9)+ EVs to increase cartilage matrix synthesis. Following dose-of-action screening, the dual EVs are loaded into a matrix metalloporoteinase 13 (MMP13)-sensitive self-assembled peptide hydrogel (KM13E) and polyethylene glycol diacrylate/gelatin methacryloyl-hydrogel microspheres (PGE), respectively. These materials are mixed to form a "microspheres-in-gel" KM13E@PGE system. In vitro, KM13E@PGE abruptly released IL-10+ EVs after 3 days and slowly released SOX9+ EVs for more than 30 days. In vivo, KM13E@PGE increased the CD206+ M2 macrophage proportion in the synovial tissue and decreased the tumor necrosis factor-α and IL-1ß levels. The aggrecan and SOX9 expressions in the cartilage tissues are significantly elevated following inflammation subsidence. This performance is not achieved using anti-inflammatory or cartilage repair therapy alone. The present study provides an injectable, integrated delivery system with spatiotemporal control release of dual EVs, and may inspire logic-gates strategies for OA treatment.

Correlation Between Serum 1,25(OH)2D3, Serum Phosphorus, and Parathyroid Hormone and Parathyroid Function After Central Lymph Node Dissection in Patients with Papillary Thyroid Carcinoma.

This work was to demonstrate the relationship between serum 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), serum phosphorus (SP), and parathyroid hormone (PTH) and parathyroid function after central lymph node dissection (CLND) in patients with papillary thyroid carcinoma (PTC). 200 PTC patients after CLND were included, who were rolled into a control group (CG) (n = 89 cases without hypoparathyroidism) and an observation group (OG) (n = 111 cases with complicated hypoparathyroidism). The 1,25(OH)2D3, SP, and PTH levels were detected, and the diagnostic effect of these indicators was assessed. The serum PTH levels of patients in CG after surgery were normal relative to those before surgery, while the serum PTH of patients in OG was relatively lower. 1,25(OH)2D3 concentration of patients in OG was also inferior to CG, while the SP level was superior (P < 0.05). Hypoparathyroidism was positively correlated with serum PTH (r = 0.382) and 1,25(OH)2D3 (r = 0.321) and negatively correlated with SP (r = - 0.211). The area under the curve (AUC) (0.893), sensitivity (90.83%), and specificity (94.77%) of the joint diagnosis of 1,25(OH)2D3 + SP + PTH were greatly superior to those of the single diagnosis and the pairwise diagnosis with the three indicators (P < 0.05). Hypoparathyroidism in patients with PTC after CLND surgery was positively correlated with 1,25(OH)2D3 and PTH and negatively correlated with SP concentration. In addition, the combination diagnosis of 1,25(OH)2D3, PTH, and SP worked well.

Naringenin attenuated airway cilia structural and functional injury induced by cigarette smoke extract via IL-17 and cAMP pathways.

BACKGROUND: Cigarette smoke impairs mucociliary clearance via mechanisms such as inflammatory response and oxidative injury, which in turn induces various respiratory diseases. Naringenin, a naturally occurring flavonoid in grapes and grapefruit, has exhibited pharmacological properties such as anti-inflammatory, expectorant, and antioxidant properties. However, it is still unclear whether naringenin protects airway cilia from injury caused by cigarette smoke. PURPOSE: This study aimed to investigate the effect of naringenin on cigarette smoke extract (CSE)-induced structural and functional abnormalities in airway cilia and highlight the potential regulatory mechanism. METHODS: Initially, network pharmacology was used to predict the mechanism of action of naringenin in ciliary disease. Next, HE staining, immunofluorescence, TEM, qRT-PCR, western blot, and ELISA were performed to assess the effects of naringenin on airway cilia in tracheal rings and air-liquid interface (ALI) cultures of Sprague Dawley rats after co-exposure to CSE (10% or 20%) and naringenin (0, 25, 50, 100 µM) for 24 h. Finally, transcriptomics and molecular biotechnology methods were conducted to elucidate the mechanism by which naringenin protected cilia from CSE-induced damage in ALI cultures. RESULTS: The targets of ciliary diseases regulated by naringenin were significantly enriched in inflammation and oxidative stress pathways. Also, the CSE decreased the number of cilia in the tracheal rings and ALI cultures and reduced the ciliary beat frequency (CBF). However, naringenin prevented CSE-induced cilia damage via mechanisms such as the downregulation of cilia-related genes (e.g., RFX3, DNAI1, DNAH5, IFT88) and ciliary marker proteins such as DNAI2, FOXJ1, and ß-tubulin IV, the upregulation of inflammatory factors (e.g., IL-6, IL-8, IL-13), ROS and MDA. IL-17 signaling pathway might be involved in the protective effect of naringenin on airway cilia. Additionally, the cAMP signaling pathway might also be related to the enhancement of CBF by naringenin. CONCLUSION: In this study, we first found that naringenin reduces CSE-induced structural disruption of airway cilia in part via modulation of the IL-17 signaling pathway. Furthermore, we also found that naringenin enhances CBF by activating the cAMP signaling pathway. This is the first report to reveal the beneficial effects of naringenin on airway cilia and the potential underlying mechanisms.

Naringenin regulates cigarette smoke extract-induced extracellular vesicles from alveolar macrophage to attenuate the mouse lung epithelial ferroptosis through activating EV miR-23a-3p/ACSL4 axis.

BACKGROUND: Alveolar macrophages are one of the momentous regulators in pulmonary inflammatory responses, which can secrete extracellular vesicles (EVs) packing miRNAs. Ferroptosis, an iron-dependent cell death, is associated with cigarette smoke-induced lung injury, and EVs have been reported to regulate ferroptosis by transporting intracellular iron. However, the regulatory mechanism of alveolar macrophage-derived EVs has not been clearly illuminated in smoking-related pulmonary ferroptosis. Despite the known anti-ferroptosis effects of naringenin in lung injury, whether naringenin controls EVs-mediated ferroptosis has not yet been explored. PURPOSE: We explore the effects of EVs from cigarette smoke-stimulated alveolar macrophages in lung epithelial ferroptosis, and elucidate the EV miRNA-mediated pharmacological mechanism of naringenin. STUDY DESIGN AND METHODS: Differential and ultracentrifugation were conducted to extract EVs from different alveolar macrophages treatment groups in vitro. Both intratracheal instilled mice and treated epithelial cells were used to investigate the roles of EVs from alveolar macrophages involved in ferroptosis. Small RNA sequencing analysis was performed to distinguish altered miRNAs in EVs. The ferroptotic effects of EV miRNAs were examined by applying dual-Luciferase reporter assay and miRNA inhibitor transfection experiment. RESULTS: Here, we firstly reported that EVs from cigarette smoke extract-induced alveolar macrophages (CSE-EVs) provoked pulmonary epithelial ferroptosis. The ferroptosis inhibitor ferrostatin-1 treatment reversed these changes in vitro. Moreover, EVs from naringenin and CSE co-treated alveolar macrophages (CSE+Naringenin-EVs) markedly attenuated the lung epithelial ferroptosis compared with CSE-EVs. Notably, we identified miR-23a-3p as the most dramatically changed miRNA among Normal-EVs, CSE-EVs, and CSE+Naringenin-EVs. Further experimental investigation showed that ACSL4, a pro-ferroptotic gene leading to lipid peroxidation, was negatively regulated by miR-23a-3p. The inhibition of miR-23a-3p diminished the efficacy of CSE+Naringenin-EVs. CONCLUSION: Our findings firstly provided evidence that naringenin elevated the EV miR-23a-3p level from CSE-induced alveolar macrophages, thereby inhibiting the mouse lung epithelial ferroptosis via targeting ACSL4, and further complemented the mechanism of cigarette-induced lung injury and the protection of naringenin in a paracrine manner. The administration of miR-23a-3p-enriched EVs has the potential to ameliorate pulmonary ferroptosis.

Identification of the active compounds in the Yi-Fei-San-Jie formula using a comprehensive strategy based on cell extraction/UPLC-MS/MS, network pharmacology, and molecular biology techniques.

BACKGROUND: Chinese herbal formulae has multiple active constituents and targets, and the good clinical response is encouraging more scientists to explore the bio-active ingredients in such complex systems. Yi-Fei-San-Jie formula (YFSJF) is commonly used to treat patients with lung cancer in South China; however, its bio-active ingredients remain unknown. PURPOSE: We investigated the bio-active ingredients of the YFSJF using a novel comprehensive strategy. METHODS: A549 cell extraction coupled with ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS) was used for the screening of potential bio-active ingredients. Network pharmacology approach and molecular dynamics simulation were performed for the screening of targets. Surface plasmon resonance (SPR) assay and molecular biology techniques were used to verify the targets. RESULTS: Nine A549 cell membrane-binding compounds were identified through cell extraction/UPLC-MS/MS. Five compounds, namely ginsenoside Ro, ginsenoside Rb1, ginsenoside Rc, peimisine, and peimine were cytotoxic to A549 cells, and they were considered the bio-active ingredients of the YFSJF in vitro. Network pharmacology analysis revealed that TGFBR2 is the key target and the TGFß pathway is the key pathway targeted by YFSJF in non-small cell lung cancer. Peimisine showed an affinity to TGFBR2 using molecular docking and dynamic stimulation, which was confirmed using surface plasmon resonance spectroscopy. The molecular biology-based analysis further confirmed that peimisine targets TGFBR2 and can reverse A549 epithelial-mesenchymal transition by inhibiting the TGFß pathway. CONCLUSION: Taken together, cell extraction/UPLC-MS/MS, network pharmacology, and molecular biology-based analysis comprise a feasible strategy to explore active ingredients in YFSJF.

A Mechanism Exploration for the Yi-Fei-San-Jie Formula against Non-Small-Cell Lung Cancer Based on UPLC-MS/MS, Network Pharmacology, and In Silico Verification.

Non-small-cell lung cancer (NSCLC) is one of the most prevalent cancers worldwide. A Yi-Fei-San-Jie formula (YFSJF), widely used in NSCLC treatment in south China, has been validated in clinical studies. However, the pharmacological mechanism behind it remains unclear. In this study, 73 compounds were identified using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), with 58 enrolled in network pharmacology. The protein-protein interaction network, functional enrichment analysis, and compound-target-pathway network were constructed using 74 overlapping targets from 58 drugs and NSCLC. YFSJF has many targets and pathways in the fight against NSCLC. PIK3R1, PIK3CA, and AKT1 were identified as key targets, and the PI3K/AKT pathway was identified as the key pathway. According to the Human Protein Atlas (THPA) database and the Kaplan-Meier Online website, the three key targets had varying expression levels in normal and abnormal tissues and were linked to prognosis. Molecular docking and dynamics simulations verified that hub compounds have a strong affinity with three critical targets. This study revealed multiple compounds, targets, and pathways for YFSJF against NSCLC and suggested that YFSJF might inhibit PIK3R1, PIK3CA, and AKT1 to suppress the PI3K/AKT pathway and play its pharmacological role.

Values of combined C-reactive protein, procalcitonin and serum amyloid A in differential diagnosis of bacterial and non-bacterial community acquired pneumonia in children.

This research aimed to explore the clinical value of C-reactive protein (CRP), procalcitonin (PCT), and serum amyloid A (SAA) in early diagnosis of bacterial pneumonia. CRP, PCT, and SAA levels of children with bacterial pneumonia, children with non-bacterial pneumonia, and healthy children were compared. The sensitivity and specificity of CRP, PCT, and SAA in the diagnosis of bacterial pneumonia in children were compared. CRP, PCT, and SAA levels were significantly lower in healthy children when compared with children with Community acquired pneumonia (CAP). ROC analyses showed that CRP, PCT, and SAA all had good accuracy in distinguishing bacterial pneumonia from non-bacterial pneumonia. The combination of CRP, PCT, and SAA further enhanced the accuracy in distinguishing bacterial pneumonia from non-bacterial pneumonia. In conclusion, the expression levels of CRP, PCT, and SAA could indicate the status of bacterial pneumonia. The combined test of CRP, PCT, and SAA had the highest diagnostic accuracy.

Injectable MMP1-sensitive microspheres with spatiotemporally controlled exosome release promote neovascularized bone healing.

Bone marrow mesenchymal stromal cell-derived exosomes (BMSC-Exos) can recruit stem cells for bone repair, with neovessels serving as the main migratory channel for stem cells to the injury site. However, existing exosome (Exo) delivery strategies cannot reach the angiogenesis phase following bone injury. To that end, an enzyme-sensitive Exo delivery material that responds to neovessel formation during the angiogenesis phase was designed in the present study to achieve spatiotemporally controlled Exo release. Herein, matrix metalloproteinase-1 (MMP1) was found to be highly expressed in neovascularized bone; as a result, we proposed an injectable MMP1-sensitive hydrogel microspheres (KGE) made using a microfluidic chip prepared by mixing self-assembling peptide (KLDL-MMP1), GelMA, and BMSC-Exos. The results revealed that KGE microspheres had a uniform diameter of 50-70 µm, ideal for minimally invasive injection and could release exosomes in response to MMP1 expression. In vitro experiments demonstrated that KGE had less cytotoxicity and could promote the migration and osteodifferentiation of BMSCs. Furthermore, in vivo experiments confirmed that KGE could promote bone repair during angiogenesis by recruiting CD90+ stem cells via neovessels. Collectively, our results suggest that injectable enzyme-responsive KGE microspheres could be a promising Exo-secreting material for accelerating neovascularized bone healing. STATEMENT OF SIGNIFICANCE: Exosomes can spread through blood vessels and activate stem cells to participate in bone repair, but under normal circumstances, exosomes lacking sustained-release delivery materials cannot be maintained until the angiogenesis phase. In this study, we found that MMP1 was highly expressed in neovascularized bone, then we proposed an MMP1-sensitive injectable microsphere that carries exosomes and responds temporally and spatially to neovascularization, which maximizes the ability of exosomes to recruit stem cells. Different from previous strategies that focus on promoting angiogenesis to accelerate bone healing, this is a brand new delivery strategy that is stimuli-responsive to neovessel formation. In addition, the preparation of self-assembled peptide microspheres by a microfluidic chip is also proposed for the first time.

Value of dynamic contrast-enhanced magnetic resonance imaging in combination with mammography for screening early-stage breast cancer.

Objective: To study the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in combination with mammography for screening early-stage breast cancer. Methods: Ninety-three female patients visiting Zhejiang Zhuji Hospital of Traditional Chinese Medicine from January 2020 to March 2022 were enrolled to receive DCE-MRI and mammography. The diagnostic efficiencies of different methods were assessed with pathological diagnosis as the golden standard. The factors affecting diagnostic sensitivity were investigated based on clinicopathological characteristics. Results: Forty-one patients were diagnosed as malignant pathological changes by DCE-MRI, and the signs were unclear boundary with surrounding tissues and irregular or unsmooth edges. The maximum linear slope and ratio of the maximum linear SlopeR of malignant pathological changes were significantly larger than those of benign pathological changes (P<0.05). Forty-five patients were diagnosed as malignant pathological changes by mammography combined with DCE-MRI. Compared to single diagnosis method, the combined diagnosis had significantly increased sensitivity, specificity, accuracy, positive predictive value and negative predictive value, and decreased rates of missed diagnosis and misdiagnosis (P<0.05). Lesion diameter was an independent risk factor affecting the diagnostic sensitivity (P<0.05). Conclusion: Mammography and DCE-MRI play key roles in the early diagnosis of breast cancer, and their combination can increase the diagnostic efficiency.

Naringenin attenuates inflammation, apoptosis, and ferroptosis in silver nanoparticle-induced lung injury through a mechanism associated with Nrf2/HO-1 axis: In vitro and in vivo studies.

With the wide application of silver nanoparticles (AgNPs), their potential damage to human health needs to be investigated. Lung is one of the main target organs after inhalation of AgNPs. Naringenin has been reported to have anti-inflammatory and anti-oxidative properties. This study aims to evaluate the protective effects of naringenin against AgNPs-induced lung injury and determine the underlying mechanism. In in vivo experiments, AgNPs were intratracheally instilled into ICR mice (l mg/kg) to establish a lung injury model. These mice were then treated with naringenin by oral gavage (25, 50, 100 mg/kg) for three days. Naringenin treatment decreased the levels of white blood cells, neutrophils, and lymphocytes in the blood, ameliorated lung injury, suppressed the release of pro-inflammatory cytokines, normalized ferroptotic markers and prevented oxidative stress with elevating Nrf2 and HO-1 protein expressions in lung. In in vitro experiments, BEAS-2B cells were firstly treated with AgNPs (320 µg/mL) and then naringenin (25, 50, and 100 µM), respectively. Naringenin attenuated AgNPs-induced oxidative stress and inflammatory response. Moreover, naringenin attenuated AgNPs-induced apoptosis with modulated low BAX, CytC, cleaved Caspase9, cleaved Caspase3 but high Bcl2. Furthermore, naringenin effectively decreased ferroptotic markers and increased the protein expressions of Nrf2 and HO-1, as well as increased the nuclear translocation of Nrf2. Importantly, the anti-apoptotic and anti-ferroptotic effects of naringenin in BEAS-2B cells were found to be at least partially Nrf2-dependent. These results indicated that naringenin exerted anti-inflammation, anti-apoptosis, and anti-ferroptosis effects and protected against AgNPs-induced lung injury at least partly via activating Nrf2/HO-1 signaling pathway.

Naringenin suppresses BEAS-2B-derived extracellular vesicular cargoes disorder caused by cigarette smoke extract thereby inhibiting M1 macrophage polarization.

Extracellular vesicles (EVs)-mediated epithelium-macrophage crosstalk has been proved to maintain lung homeostasis in cigarette smoke-induced lung diseases such as chronic obstructive pulmonary disease (COPD). In our previous study, we found that EVs derived from cigarette smoke extract (CSE) treated BEAS-2B promoted M1 macrophage polarization, which probably accelerated the development of inflammatory responses. Naringenin has been proved to suppress M1 macrophage polarization, but whether naringenin regulates macrophage polarization mediated by EVs has not been reported. In this study, we firstly found that EVs derived from naringenin and CSE co-treated BEAS-2B significantly inhibited the expression of CD86 and CD80 and the secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß, inducible nitric oxide synthase (iNOS), and IL-12 in macrophage induced by EVs derived from CSE-treated BEAS-2B. Further research revealed that naringenin downregulated BEAS-2B-derived EVs miR-21-3p which targeted phosphatase and tensin homolog deleted on chromosome ten/protein kinase B (PTEN/AKT) cascade in macrophages and then suppressed M1 macrophage polarization. Subsequent proteomics suggested that naringenin decreased BEAS-2B-derived EVs poly ADP-ribose polymerase (PARP)1 expression thereby suppressing M1 macrophage polarization probably. Our study provides novel pharmacological references for the mechanism of naringenin in the treatment of cigarette smoke-induced lung inflammatory diseases.

Ultrasound-guided totally implantable venous access ports placement via right brachiocephalic vein in pediatric population: A clinical debut.

BACKGROUND AND OBJECTIVES: To investigate the feasibility and safety of ultrasound-guided totally implantable venous access ports (TIVAPs) via the right brachiocephalic vein (BCV) in pediatric patients. METHODS: A single-institute retrospective review was performed on 35 pediatric patients with predominantly hematological malignancies (88.6%) who underwent TIVAP implantation via ultrasound-guided right BCV approach from July 2018 to June 2021. The catheter tip was adjusted to be positioned at the cavoatrial junction under pulsed fluoroscopic guidance. Technical success rate, procedural information, and TIVAP-related complications were evaluated. RESULTS: All the pediatric TIVAP devices were successfully implanted via right BCV access. Venous access was successful by first attempt in 32 children (91%), two cases (5.7%) required a second attempt, and one patient (2.9%) required a third attempt. The mean procedural time was 44.6 ± 6.4 minutes (range: 34-62 minutes). No intraoperative complications occurred. The average TIVAP indwelling time was 564 ± 208 days (range: 193-1014 days), with a cumulative 19,723 catheter-days. Overall, three patients (8.6%) experienced four postoperative complications (two cases of local hematoma and two catheter dysfunctions) at a rate of 0.2 per 1000 catheter-days. No other complications such as wound dehiscence, delayed incision healing, catheter-related thrombosis (CRT), catheter malposition/fracture, surgical site infection, catheter-related bloodstream infection (CRBSI), pinch-off syndrome, and drug extravasation were observed during follow-up. CONCLUSIONS: Ultrasound-guided right BCV access for TIVAP placement in pediatric patients appears to be technically feasible, safe, and effective. Further large-sample, prospective studies are warranted.

A Novel Drug Combination of Mangiferin and Cinnamic Acid Alleviates Rheumatoid Arthritis by Inhibiting TLR4/NFκB/NLRP3 Activation-Induced Pyroptosis.

Growing evidence shows that Baihu-Guizhi decoction (BHGZD), a traditional Chinese medicine (TCM)-originated disease-modifying anti-rheumatic prescription, may exert a satisfying clinical efficacy for rheumatoid arthritis (RA) therapy. In our previous studies, we verified its immunomodulatory and anti-inflammatory activities. However, bioactive compounds (BACs) of BHGZD and the underlying mechanisms remain unclear. Herein, an integrative research strategy combining UFLC-Q-TOF-MS/MS, gene expression profiling, network calculation, pharmacokinetic profiling, surface plasmon resonance, microscale thermophoresis, and pharmacological experiments was carried out to identify the putative targets of BHGZD and underlying BACs. After that, both in vitro and in vivo experiments were performed to determine the drug effects and pharmacological mechanisms. As a result, the calculation and functional modularization based on the interaction network of the "RA-related gene-BHGZD effective gene" screened the TLR4/PI3K/AKT/NFκB/NLRP3 signaling-mediated pyroptosis to be one of the candidate effective targets of BHGZD for reversing the imbalance network of "immune-inflammation" during RA progression. In addition, both mangiferin (MG) and cinnamic acid (CA) were identified as representative BACs acting on that target, for the strong binding affinities between compounds and target proteins, good pharmacokinetic features, and similar pharmacological effects to BHGZD. Notably, both BHGZD and the two-BAC combination of MG and CA effectively alleviated the disease severity of the adjuvant-induced arthritis-modified rat model, including elevating pain thresholds, relieving joint inflammation and bone erosion via inhibiting NF-κB via TLR4/PI3K/AKT signaling to suppress the activation of the NLRP3 inflammasome, leading to the downregulation of downstream caspase-1, the reduced release of IL-1ß and IL-18, and the modulation of GSDMD-mediated pyroptosis. Consistent data were obtained based on the in vitro pyroptosis cellular models of RAW264.7 and MH7A cells induced by LPS/ATP. In conclusion, these findings offer an evidence that the MG and CA combination identified from BHGZD may interact with TLR4/PI3K/AKT/NFκB signaling to inhibit NLRP3 inflammasome activation and modulate pyroptosis, which provides the novel representative BACs and pharmacological mechanisms of BHGZD against active RA. Our data may shed new light on the mechanisms of the TCM formulas and promote the modernization development of TCM and drug discovery.

7,8-Dihydroxycoumarin Alleviates Synaptic Loss by Activated PI3K-Akt-CREB-BDNF Signaling in Alzheimer's Disease Model Mice.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and is clinically characterized by the impairment of memory and cognition. Accumulation of ß-amyloid (Aß) in the brain is considered as a key process in the development of AD because it impairs the synapses' function to impair memory formation. Recent research studies have indicated that a group of edible plant-derived Thymelaeaceae compounds known as coumarin may exert particularly powerful actions on alleviating learning and memory impairment. 7,8-Dithydroxycoumarin (7,8-DHC), a bioactive component of coumarin derived from Thymelaeaceae, showed its function in neuroprotection before. In this study, we found that 7,8-DHC was able to mitigate Aß accumulation via reducing the level of BACE1 and increasing the level of ADAM17 and ADAM10. More importantly, we found that 7,8-DHC could mitigate memory impairment, promote the dendrite branch density, and increase synaptic protein expression via activating PI3K-Akt-CREB-BDNF signaling. Hence, these results suggested that 7,8-DHC represented a novel bioactive therapeutic agent in mitigating Aß deposition and synaptic loss in the process of treating AD.

Experimental study on the desorption effect of penetrant on gas-containing coal.

Two non-ionic reagents, polyethylene glycol 4000 and Tween-80, two anionic reagents, sodium dodecyl benzenesulfonate and sodium lauryl sulfate, and a mixture of these non-ionic and anionic reagents were used as penetrants. The processes of replacement desorption and relief-pressure desorption of gas-containing coal were studied, the influence of the penetrant on the amount of gas replacement desorption and relief-pressure desorption was explored, and the change rule of the amounts of gas replacement desorption and relief-pressure desorption was analysed. The results show that the increase rate of the replacement desorption amount of the mixed penetrant is 11.81%-34.75%, and the decrease rate of the relief-pressure desorption amount is 51.68%-72.69%, which are higher values than those with a single penetrant. As the mass fraction of penetrant increases within the range of 0.5%~2%, the capacity of gas replacement desorption and hindering gas relief-pressure desorption will increase. At the same mass fraction, the effect of the mixed penetrant is better than that of the anionic penetrant, which in turn is better than that of the non-ionic penetrant.

Study on the Efficacy and Safety of Ambroxol Combined with Methylprednisolone in Patients with Acute Lung Injury.

BACKGROUND: There is no better treatment method towards paraquat-induced acute lung injury (ALI) at present. Ambroxol combined with methylprednisolone exhibits a significant improvement effect on ALI treatment, whereas their mechanism in ALI is still unclear. METHODS: 64 patients with ALI caused by paraquat poisoning brought to our hospital from January 2015 to January 2018 were selected. They were separated into a combined treatment group (CTG) and a routine treatment group (RTG) on the basis of different treatment methods. The survival of patients was observed after 7 days of treatment. Arterial blood gas, oxygen partial pressure (PaO2), partial pressure of carbon dioxide (PaCO2), oxygenation index (PaO2/FiO2), patient's spontaneous respiratory rate (RR), tidal volume (VT), and positive end-expiratory pressure (PEEP) were observed before and after treatment for 7 days. Interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were analyzed. The differences of indexes between the dead patients and the survivors were observed, and the potential predictive value of death was analyzed. RESULTS: After treatment, the indexes of patients were significantly improved in both groups compared with those before therapy. Further comparison showed that the improvement of PaO2, PaCO2, and PaO2/FiO2 in CTG was obviously higher than that in RTG (p < 0.05). The improvement of RR, PEEP, and VT in CTG was obviously higher than that in RTG (p < 0.05). The decreased degree of IL-6 and TNF-α in CTG was higher than that in RTG (p < 0.05). The 7-day mortality rate of 64 patients was 39.06%, and there was no obvious difference in the 7-day survival rate in both groups (p = 0.649). IL-6 and TNF-α were expected to be potential prediction indexes of paraquat-induced ALI. CONCLUSION: Ambroxol combined with methylprednisolone significantly improved the oxygen partial pressure and oxygenation index of patients with paraquat-induced ALI and inhibited the inflammatory response of patients.

Facile Preparation of a Rhodamine B Derivative-Based Fluorescent Probe for Visual Detection of Iron Ions.

Iron ions play an important role in our lives. Excessive or lack of iron ion intake leads to many diseases. At the same time, the water environment is easily polluted by these metal ions with the acceleration of industrialization. Therefore, the detection of iron ions in the water environment and the human body is particularly important. In this paper, we prepared a RhB-EDA fluorescent probe by condensing rhodamine B (RhB) with ethylenediamine (EDA) for high recognition of Fe3+. A RhB-EDA molecule itself is colorless and has no fluorescence emission in an alcohol solution. When Fe3+ was added, the lactam ring structure of the fluorescent probe opened, and the UV and fluorescence spectra changed. At the same time, the color of the mixed solution gradually deepened toward pink. Therefore, dual spectral detection and naked-eye observation of Fe3+ were realized. In addition, with the decrease of the pH value and the prolongation of chelating time, the ultraviolet absorbance and fluorescence emission intensity were enhanced and the color of the mixed solution deepened. The RhD-EDA fluorescent probe is simple and accurate and provides good technical support for the detection of Fe3+.

miRNAomics analysis reveals the promoting effects of cigarette smoke extract-treated Beas-2B-derived exosomes on macrophage polarization.

Inhalation of cigarette smoke induces airway and parenchyma inflammation that predisposes smokers to multiple lung diseases such as COPD. Macrophage polarization, an important specifying feature of inflammation, is involved in the progression of pulmonary inflammation. Exosomes and their loaded miRNAs provide a medium for cross-talk between alveolar macrophages and lung epithelial cells to maintain lung homeostasis. In this study, we treated Beas-2B with CSE to speculate the effects of Beas-2B-derived exosomes on macrophage polarization and performed exosomal miRNAomics analysis to explore the mechanism. We found that CSE-treated Beas-2B-derived exosomes could not only increase the percentages of CD86+, CD80+ CD163+, and CD206+ cells but also induce the secretion of TNF-α, IL-6, iNOS, IL-10, Arg-1, and TGF-ß, indicating both M1 and M2 polarization of RAW264.7 macrophages were promoting. We performed miRNAomics analysis to identify 27 differentially expressed exosomal miRNAs such as miR-29a-3p and miR-1307-5p. Next, we obtained 14942 target genes of these miRNAs such as SCN1A and PLEKHA1 through the prediction of TargetScan and miRanda. We utilized KEGG enrichment analysis for these targets to identify potential pathways such as the PI3K-Akt signaling pathway and the MAPK signaling pathway on the regulation of macrophage polarization. We further found that miR-21-3p or miR-27b-3p may play critical roles in the promotion of CSE-Exo on macrophage polarization by miRNA interference. Collectively, this study provided novel information for diagnostic and therapeutic tactics of cigarette smoke-related lung diseases.

Non-invasive prediction of lymph node status for patients with early-stage invasive breast cancer based on a morphological feature from ultrasound images.

BACKGROUND: This study aimed to estimate the value of a morphological feature on ultrasound (US) for preoperative diagnosis of axillary lymph node (ALN) status in patients with early-stage invasive breast cancer (ESIBC). METHODS: In this retrospective work, a total of 239 ESIBC patients, were recruited, and their preoperative US images and postoperative pathology results were collected. The relationship between US images based on morphological features and ALN metastasis was investigated. The tumor circularity and US-reported ALN status were developed as a nomogram to predict the ALN status. RESULTS: Among the 239 participants, 82 (34.31%) had ALN metastasis, and 157 (65.69%) did not. There was a statistically significant difference in tumors between participants diagnosed with and without ALN metastasis. The median value was 0.47 vs. 0.62 (P<0.001) in the training group, respectively, and the value was 0.50 vs. 0.60 (P<0.001) in the validation group, respectively. The clinical model nomogram was shown to have high efficiency in predicting ALN status among our research population. The area under the curve (AUC) was 0.89 in the training group and 0.90 in the validation group and the accuracy was 85.79% and 81.63%, respectively. CONCLUSIONS: The clinical model nomogram based on tumor circularity and US-reported ALN status is a non-invasive approach for ALN metastasis prediction in ESIBC patients with high efficacy.