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Effective bleeding control is essential for the reduction of traumatic deaths among civilians and military personnel, particularly for physical visceral and arteriovenous injuries. Materials with good hemostatic properties have recently attracted significant scientific attention. In this study, a novel material of tranexamic acid modified porous starch (TAMPS) was produced through esterification. The structure of the final product was characterized using Fourier-transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and thermogravimetric analysis. The hemostatic effect of TAMPS was preliminarily analyzed via in vitro clotting time, mouse tail amputation model and liver injury model experiments. Hemostatic effect of TAMPS was found to be significantly better than that of the positive control Quickclean. Through the exploration of related hemostatic mechanisms, TAMPS can promote coagulation via rapid fluid absorption and high erythrocyte aggregation capacity. The in vitro cytotoxicity, acute toxicity, and hemolysis tests revealed that TAMPS is safe and nontoxic and has perfect blood compatibility. Therefore, the TAMPS has a great potential for future clinical application as a rapid and multitarget hemostatic material.

The blood–brain barrier (BBB) constitutes a major obstacle to effective delivery of drugs to the brain. Recent technological advances have led to improvements in brain-targeted drug delivery. In this review, we summarize existing technologies for efficient drug delivery across the BBB. We discuss the mechanisms of current BBB-based drug delivery strategies and introduce prospects for application in brain-targeted delivery of traditional Chinese medicine. We highlight the use of physical techniques for brain-targeted drug delivery, including electroporation, ultrasound, magnetophoresis, microneedles, microwaves, and laser. The characteristics of these techniques and relevant studies employing these approaches are discussed. In general, microneedles, lasers, ultrasound, electroporation, magnetophoresis, and microwaves are effective for drug delivery across the BBB. Notably, the synergistic effects of multiple approaches are superior to the additive effects of each technique in isolation. Our review provides guidance for the practical application of brain-targeted drug delivery techniques in an efficient and safe manner.

A new kind of photolabile protecting group (PLPG) for carboxyl moieties was designed and synthesized as the linker between resin and peptide. This group can be used for the protection of amino acid carboxyl groups. The peptide was synthesized on Nph (2‐hydroxy‐3‐(2‐nitrophenyl)‐heptanoic acid)‐derivatized resins and could be cleaved under UV exposure, thus avoiding the necessity for harsh acid‐mediated resin cleavage. The PLPG has been successfully used for solid‐phase synthesis of peptides., A photolabile protecting group (PLPG) for carboxyl derivatives was designed and synthesized. The newly derived molecule can be used for the protection of amino acid carboxyl groups and can be removed rapidly under the condition of 365 nm.

Sepsis is a common and lethal syndrome. Long non-coding RNA (lncRNA) transcript predicting survival in AKI (TapSAKI) has recently been found to serve as an important regulator in sepsis. However, the underlying mechanism of TapSAKI in sepsis pathogenesis remains largely unknown. Our data demonstrated that lipopolysaccharide (LPS)-induced HK-2 cell injury by weakening cell viability and enhancing cell apoptosis and inflammation. TapSAKI was upregulated and miR-205 was downregulated in LPS-induced HK-2 cells. TapSAKI knockdown or miR-205 overexpression alleviated LPS-induced cytotoxicity in HK-2 cells. TapSAKI sequestered miR-205 via acting as a miR-205 sponge. Moreover, the mitigating effect of TapSAKI silencing on LPS-induced HK-2 cell injury was mediated by miR-205. Additionally, the interferon regulatory factor 3 (IRF3) signaling was involved in the regulation of the TapSAKI/miR-205 axis on LPS-induced HK-2 cell damage. Our current study suggested that TapSAKI silencing relieved LPS-induced injury in HK-2 cells at least in part by sponging miR-205 and regulating the IRF3 signaling pathway, highlighting a novel understanding for sepsis pathogenesis and a promising target for this disease treatment.

In this work, a series of novel benzyl naphthyl sulfoxides/sulfones derived from Rigosertib were designed and synthesized as potential antitumor agents. The in vitro cytotoxicity against four human cancer cell lines (HeLa, MCF-7, HepG2 and SCC-15) and two normal human cell lines (HUVEC and 293T) indicated that some of the sulfones and sulfoxides possessed potent antineoplastic activity that reached nanomolar levels and relatively low toxicity to normal cells. Among them, (2-methoxy-5-((naphthalen-2-ylsulfonyl)methyl)phenyl)glycine (15b) was found to be a promising antitumor drug candidate that could significantly inhibit tumor cell migration and induce tumor cell apoptosis via the p53-Bcl-2-Bax signaling pathway at nanomolar concentrations.

Studies from our group and others have reported that 30 mW/cm2 microwave could damage the structures of rat hippocampus, as well as impair the neuronal functions. The neuroprotective effects of astragaloside, purified from Astragalus membranaceus, have been demonstrated in animal models of neurodegenerative diseases. In this study, we found that 30 mW/cm2 microwave impaired spatial learning and memory ability in rats, while astragaloside could significantly alleviate the injuries. The pathological analysis also showed that astragaloside protected neurons from microwave-induced damages, such as mitochondrial swelling and cavitation, rough endoplasmic reticulum swelling and dilation, synaptic gap disappearing, and vesicle aggregation. Moreover, microwave-induced structural damage of synapse resulted in downregulation of acetylcholine, an important neurotransmitter for information transmission, while astragaloside could protect the structure of synapse, as well as restore the acetylcholine level in rat hippocampus. Furthermore, astragaloside also accelerated the recovery of brain electroencephalogram (EEG) after microwave exposure, indicating that astragaloside could promote the normalization of neuronal functions. In conclusion, astragaloside protected the morphological structures and restored acetylcholine level in rat hippocampus, which could improve brain functions via normalizing brain EEG. Therefore, astragaloside might be a promising candidate to treat microwave-induced injuries of central nervous system (CNS).

Coumarin moiety has garnered momentous attention especially in the design of compounds with significant biological activities. In this work, a series of 3-substituted coumarin derivatives 6a-6l were synthesized and fully characterized. Most of the compounds could obviously inhibit the activity of cyclooxygenase-1 (COX-1) at the concentration of 10 µM. Besides, 6h and 6l exhibited highest inhibitory effects against COX-2 with inhibition rates of 33.48 and 35.71%, respectively. Detailed structure-activity relationships (SARs) were also discussed. In vivo studies, 6b, 6i and 6l could remarkably repress the xylene-induced ear swelling in mice at the dose of 20 mg/kg. Especially, 6l seemed to be the most effective compound at the dose of 10 mg/kg, displaying favorable anti-inflammatory activity comparable to indomethacin. All of these findings suggested that 6l might be utilized as a candidate for the treatment of inflammatory diseases.

Background: Distinguishing ICU patients with candidaemia can help with the precise prescription of antifungal drugs to create personalized guidelines. Previous prediction models of candidaemia have primarily used traditional logistic models and had some limitations. In this study, we developed a machine learning algorithm trained to predict candidaemia in patients with new-onset systemic inflammatory response syndrome (SIRS).Methods: This retrospective, observational study used clinical information collected between January 2013 and December 2017 from three hospitals. The ICU patient data were used to train 4 machine learning algorithms–XGBoost, Support Vector Machine (SVM), Random Forest (RF), ExtraTrees (ET)–and a logistic regression (LR) model to predict patients with candidaemia.Results: Of the 8,002 cases of new-onset SIRS (in 7,932 patients) included in the analysis, 137 new-onset SIRS cases (in 137 patients) were blood culture positive for candidaemia. Risk factors, such as fungal colonization, diabetes, acute kidney injury, the total number of parenteral nutrition days and renal replacement therapy, were important predictors of candidaemia. The XGBoost machine learning model outperformed the other models in distinguishing patients with candidaemia [XGBoost vs. SVM vs. RF vs. ET vs. LR; area under the curve (AUC): 0.92 vs. 0.86 vs. 0.91 vs. 0.90 vs. 0.52, respectively]. The XGBoost model had a sensitivity of 84%, specificity of 89% and negative predictive value of 99.6% at the best cut-off value.Conclusions: Machine learning algorithms can potentially predict candidaemia in the ICU and have better efficiency than previous models. These prediction models can be used to guide antifungal treatment for ICU patients when SIRS occurs.

Background Delirium is an important independent predictor of negative clinical outcomes in intensive care unit (ICU) patients. The purpose of this study was to investigate the territorial incidence of ICU delirium, its related risk factors, and short-term outcomes in Shandong Province, China, to provide precise information for territorial patient management. Methods A multicenter prospective observational study was conducted. Patients with delirium were defined as any patient with at least one positive CAM-ICU or ICDSC assessment. Demographics, admission clinical data, daily interventions provided to patients and environmental factors were collected. Results From May 1, 2018 to Jan 31, 2020, 536 noncomatose patients were ultimately eligible for the study. One hundred eighteen patients (22%) experienced delirium at least once. In the univariate analysis, age (p = 0.009), SOFA score (p = 0.006), a history of cerebrovascular disease (p = 0.044) and impaired renal function (p = 0.003) were risk factors for delirium. Most therapeutic interventions were linked to delirium in the univariate analysis, including enteral nutrition (p = 0.000), artificial airway (p = 0.021), nasogastric tube (p = 0.001), use of restraint straps (p = 0.000), and use of sedative medications, including midazolam (p = 0.003), propofol (p = 0.032) and butorphanol (p = 0.028). Among the patient’s vital signs and laboratory examinations performed on the day of assessment, body temperature, BUN levels and CRP levels were risk factors for delirium. Midazolam use, chronic renal insufficiency, physical restraints, nosogastric tube, enteral nutrition, and CRP and BUN levels were factors associated with an increased risk of delirium in the multivariate analysis. The durations of mechanical ventilation and ICU stay in patients with delirium was significantly higher than those in patients without delirium [8 (IQR: 4–14) vs 5 (IQR: 3–10) and 9 (IQR: 4–17) vs 6 (IQR: 4–12), p

Background: Delirium is associated with increased morbidity and mortality in critically ill patients. Research on risk factors for delirium allows clinicians to identify high-risk patients, which is the basis for early prevention and diagnosis. Besides the risk factors for delirium that are commonly studied, here we more focused on the less-studied therapeutic interventions for critically ill patients which are potentially modifiable. Materials and methods: A total of 320 non-comatose patients admitted to the ICU for more than 24 hrs during 9 months were eligible for the study. Delirium was screened once daily using the CAM-ICU. Demographics, admission clinical data, and daily interventions were collected. Results: Ninety-two patients (28.75%) experienced delirium at least once. Delirious patients were more likely to have longer duration of mechanical ventilation, ICU stay, and hospital stay. Most of the less-studied therapeutic interventions were linked to delirium in the univariate analysis, including gastric tube, artificial airway, deep intravenous catheter, arterial line, urinary catheter, use of vasoactive drugs, and sedative medication. After adjusting with age and ICU length of stay, mechanical ventilation (OR: 5.123; 95% CI: 2.501-10.494), Acute Physiology and Chronic Health Evaluation (APACHE) II score≥20 at admission (OR: 1.897; 95% CI: 1.045-3.441), and gastric tube (OR: 1.935, 95% CI: 1.012-3.698) were associated with increased risk of delirium in multivariate analysis. Conclusion: Delirium was associated with prolonged mechanical ventilation, ICU stay, and hospital stay. Multivariate risk factors were gastric tube, mechanical ventilation, and APACHE II score. Although being a preliminary study, this study suggests the necessity of earliest removal of tubes and catheters when no longer needed.

Jojoba (Simmondsia chinensis (Link) C.K. Schneid) is a dioecious plant in desert and semi-desert areas, e.g., the Ismailia Desert in Egypt. Jojoba oil (JJBO) is a natural slight yellow oil with the functions of skin barrier repairing and wound healing, which is dermally applied as a traditional medication or cosmetic in the Middle East. The objective of this study was to prepare JJBO dry nanoemulsion powders (JNDs) and investigate their anti-acute lung injury effects. JJBO nanoemulsions (JNEs) were prepared and then lyophilized to JNDs and the properties and simulated lung deposition were measured. Rat acute lung injury (ALI) models were established after intratracheal (i.t.) administration of lipopolysaccharide (LPS) or hydrogen peroxide (H2O2). JNDs and dexamethasone (DXM) solutions were also i.t. administered to the rats. The pathological states of lung tissues were checked. Inflammatory and oxidative factors in the lung tissues were determined using ELISA methods. NF-κB p65 and caspase-3 were measured with a Western blotting method and an immunohistochemical method, respectively. JNDs had an appropriate mass median aerodynamic diameter (MMAD) of 4.17 µm and a fine particle fraction (FPF) of 39.11%. JNDs showed higher anti-inflammatory effect on LPS-induced ALI than DXM with a decrease in total protein content and down-regulation of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and NF-κB p65. JNDs also showed higher anti-inflammatory and anti-oxidation effect on H2O2-induced ALI than DXM with elimination of reactive oxygen species (ROS), increasing of superoxide dismutase (SOD), decrease in of lipid peroxide malondialdehyde (MDA) and glutathione (GSH), and inhibition of caspase-3 expression. Moreover, i.t. JNDs attenuated bleeding and infiltrations of the inflammatory cells in the two ALI models. JNDs are a promising natural oil-contained inhalable medication for the treatment of LPS- or H2O2-induced ALI.

To investigate the clinical value of transabdominal ultrasound combined with pulse index continuous cardiac output (PICCO) in fluid resuscitation of septic shock patients, and to analyze the predictive value of survival outcomes, 68 patients with septic shock were randomly divided into the ultrasound + PICCO group and PICCO group. Compared with before treatment, blood lactic acid (BLA) was cleared, and central venous pressure (CVP) and oxygenation index were significantly increased in all patients. The oxygen binding index, central venous oxygen saturation (ScVO2), and CVP in the ultrasound + PICCO group were increased compared with the PICCO group, while BLA, mechanical ventilation time, total fluid resuscitation input and hospitalization were significantly reduced. The extravascular lung water index and shape change index were positively correlated with sequential organ failure assessment. The combination of extravascular lung water index and shape change index had higher clinical value than each alone in predicting the death of patients with septic shock. The combination of transabdominal ultrasound with PICCO is better at guiding fluid resuscitation in patients with septic shock and has a certain predictive value with respect to the survival outcome of septic shock patients.

Shengyu Zhou,1,2,* Jiawei Xu,1,* Wenqing Sun,3 Jintao Zhang,1 Fayan Zhang,4 Xuesong Zhao,5 Ximing Wang,6 Wei Zhang,7 Yu Li,1 Kang Ning,8 Yun Pan,1 Tian Liu,1 Jiping Zhao,1 Jiguang Yu,9 Yunbo Sun,10 Feng Gao,11 Rumin Zhang,12 Chunsheng Fu,13 Yu Sun,14 Xiuhe Ouyang,15 Fusen Zhang,16 Qing Hu,17 Haifeng Teng,18 Yun Li,19 Chunke Zhang,20 Wei Tan,21 Jinlai Li,22 Lixia Yin,23 Liang Dong,1 Chunting Wang5 1Department of Respiratory and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Clinical Nursing Department, School of Nursing, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 3Intensive Care Unit, Shandong Provincial Chest Hospital, Jinan, People’s Republic of China; 4College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 5Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 6Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong University, Jinan, People’s Republic of China; 7Department of Lung Disease, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 8The First Affiliated Hospital of Shandong First Medical University Shandong Provincial Qianfoshan Hospital, Jinan, People’s Republic of China; 9Department of Infectious Diseases, Qishan Hospital, Yantai, People’s Republic of China; 10Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 11Department of Infectious Disease, Linyi People’s Hospital, Linyi, People’s Republic of China; 12Department of Critical Care Medicine, Zibo Central Hospital, Zibo, People’s Republic of China; 13Liaocheng Contagion Hospital, Liaocheng, People’s Republic of China; 14Jining Hospital of Infectious Diseases, Jining, People’s Republic of China; 15Department of Respiratory and Critical Medicine, Binzhou People’s Hospital, Binzhou, People’s Republic of China; 16Intensive Care Unit, Taian City Central Hospital, Taian, People’s Republic of China; 17Department of Respiratory Medicine, Heze Municipal Hospital, Heze, People’s Republic of China; 18Weihai Municipal Hospital, Weihai, People’s Republic of China; 19Jinan Central Hospital, Jinan, People’s Republic of China; 20Weihai Central Hospital, Weihai, People’s Republic of China; 21Department of Respiratory Medicine, Weifang People’s Hospital, Weifang, People’s Republic of China; 22Intensive Care Unit, Zaozhuang Municipal Hospital, Zaozhuang, People’s Republic of China; 23Department of Respiratory Medicine, Dezhou People’s Hospital, Dezhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang Dong; Chunting Wang Email dl5506@126.com; wcteicu@126.comBackground: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel pathogen, has caused an outbreak of coronavirus disease 2019 (COVID-19) that has spread rapidly around the world. Determining the risk factors for death and the differences in clinical features between severely ill and critically ill patients with SARS-CoV-2 pneumonia has become increasingly important.Aim: This study was intended to provide insight into the difference between severely ill and critically ill patients with SARS-CoV-2 pneumonia.Methods: In this retrospective, multicenter cohort study, we enrolled 62 seriously ill patients with SARS-CoV-2 pneumonia who had been diagnosed by March 12, 2020. Clinical data, laboratory indexes, chest images, and treatment strategies collected from routine medical records were compared between severely ill and critically ill patients. Univariate and multivariate logistic regression analyses were also conducted to identify the risk factors associated with the progression of patients with severe COVID-19.Results: Of the 62 patients with severe or critical illness, including 7 who died, 30 (48%) patients had underlying diseases, of which the most common was cardiovascular disease (hypertension, 34%, and coronary heart disease, 5%). Compared to patients with severe disease, those with critical disease had distinctly higher white blood cell counts, procalcitonin levels, and D-dimer levels, and lower hemoglobin levels and lymphocyte counts. Multivariate regression showed that a lymphocyte count less than 109/L (odds ratio 20.92, 95% CI 1.76– 248.18; p=0.02) at admission increased the risk of developing a critical illness.Conclusion: Based on multivariate regression analysis, a lower lymphocyte count (< 109/L) on admission is the most critical independent factor that is closely associated with an increased risk of progression to critical illness. Age, underlying diseases, especially hypertension and coronary heart disease, elevated D-dimer, decreased hemoglobin, and SOFA score, and APACH score also need to be taken into account for predicting disease progression. Blood cell counts and procalcitonin levels for the later secondary bacterial infection have a certain reference values.Keywords: SARS-CoV-2, COVID-19, clinical features, severely ill patients, critically ill patients

Human activities in the areas of high altitude have increased significantly recently. Brain is highly sensitive to changing of oxygen pressure due to high altitude, and this physiological response may lead to serious brain injury, such as learning and memory disabilities. Puerarin is a phytoestrogen with many pharmacological activities, such as treatment of neurological disorders. However, most of current drugs can not easily enter brain through the blood–brain barrier (BBB). The nose-to-brain route can bypass BBB for brain-targeting. Here, thermosensitive in situ hydrogels (TISGs) of puerarin were prepared with poloxamers 407, poloxamers 188 and propylene glycol to improve bioavailability and brain targeting. In vitro drug release in simulated nasal fluids, rheological properties and cilia toxicity of puerarin TISGs were explored. The pharmacodynamics and pharmacokinetics of puerarin by intranasal (i.n.) and oral (p.o.) administrations were also evaluated. The viscosity of puerarin TISGs tended to increase obviously with increased temperature. The puerarin release profile and transmucosal process of puerarin TISGs could be described with the first-order kinetics equation, depending on drug diffusion. The cilia toxicity of puerarin TISGs was not obvious. Rat models of hypobarism/hypoxia-induced brain injury were established with a hypobaric simulation chamber. Morris water maze and open filed tests indicated that puerarin TISGs improved the spatial memory and spontaneous exploratory behavior of the rats suffering from hypoxia-induced brain injury. Furthermore, puerarin TISGs decreased the level of oxidative stress cytokines (malondialdehyde (MDA) and glutathione (GSH)) in the peripheral circulation, alleviated the cerebral histological lesions, and relieved the expression of hypoxia-inducible factor-1α (HIF-1α). Intranasal puerarin TISGs were absorbed quickly with a shorter Tmax (10.0 ± 5.7 min) compared to that of oral puerarin (36 ± 13.4 min). In addition, the relative bioavailability of i.n. puerarin TISGs was high to 300% compared to oral administration of puerarin. The area under the curve (AUC) of brain after i.n. administration of puerarin TISGs was 954.5 ± 335.1 h.ng/mL, while no puerarin was detected in the brain after oral administration. Therefore, i.n. puerarin TISGs led to excellent brain targeting effect. Puerarin TISGs are an effective neuroprotector formulation for prevention of brain injury induced by acute high-altitude hypoxia.

Continuous blood purification technology such as hemodiafiltration has been used worldwide for saving patients suffering from severe diseases or organ function failure, especially in the intensive care unit and emergency setting. The filters as core devices are commonly made of polymer materials as hollow fiber membranes. However, the membrane is often inductively blocked by blood clot formation due to its interactions with blood components. Heparin is the anticoagulant often used in clinical practice for anti-coagulation. Recently, heparin is also employed to modify the hollow fiber membranes either chemically or physically to improve the filtration performance. This review summarizes recent advances in methodology for surface heparinization of such hollow fiber membranes, and their filtration performance improvement. The review also provides expert opinions for further research in this rapidly expanding field.

Given that C-glucosylisoflavones often possess promising biological activities, the development of an efficient synthetic method for this type of molecules is useful for drug discovery. Accordingly, a highly efficient five-step strategy was developed for the total synthesis of puerarin, an isoflavone C-glycoside. An alkyl substituent 4-CH3OC6H4CH2CH2 with an electron-donating group on the aromatic ring was used to enhance the reactivity of phenol and the regioselectivity of O-C rearrangement of phenol glycoside. Thus, coupling of the ethylbenzene derivative of a phenol 1c with glycosyl trifluoroacetimidate 2 resulted in C-glycoside 3c in a 46.2% yield, which was easily de-tert-butylated with trifluoroacetic acid and oxidized with 2,3-dicyano-5,6-dichlorobenzoquinone to produce deoxybenzoin 5. The ring closure reaction of 5 followed by deprotection gave puerarin. This new synthetic strategy is also suitable for the total synthesis of other C-glucosylisoflavones.

In our previous study, advanced glycosylation end-product specific receptor (RAGE) was observed to bind to S100A8/A9 and cause epithelial mesenchymal transition (EMT). The results from target gene prediction revealed that microRNA (miR)-185-5p had a RAGE binding site. However, the function of miR-185-5p in the invasion and migration of breast cancer remains ambiguous. In the present study, the expression of miR-185-5p was examined in breast cancer tissues and cells. Clinical features revealed a negative correlation between miR-185-5p and tumor size, as well as in tumor differentiation and lymph node metastasis in breast cancer. In addition, miR-185-5p was negatively associated with RAGE, and this miRNA reversed the EMT of breast cancer by modulating RAGE in vitro. In addition, miR-185-5p inhibited the S100A8/A9-induced EMT of breast cancer cells by the nuclear factor-κB/Snail signaling pathway. Notably, miR-185-5p upregulation inhibited the F-actin polymerization induced by S100A8/A9 in breast cancer. Furthermore, overexpression of miR-185-5p and reduction of RAGE inhibited lung metastasis node in vivo. Thus, miR-185-5p represents a potential therapeutic target in breast cancer by modulating RAGE.

Acute kidney injury (AKI) is accompanied with life-threatening sepsis. It is necessary to develop effective therapy agent or strategy for treating AKI. LPS is a primary pathogenic factor that induces sepsis. Glucose-regulated protein 78 (GRP78) is closely related to cell injuries. The objective of this study was to examine the role of GRP78 in LPS-induced AKI. Cell counting kit-8 (CCK-8) assay and flow cytometry (FCM) were respectively performed to assess the cell viability and apoptosis. Available commercial kits were used to detect the reactive oxygen species (ROS) contents and the activity of oxidative indicators. The expressions of the relevant factors were determined by real-time PCR (RT-PCR) and Western blot. The results showed that the expression of GRP78 was apparently increased by LPS treatment, and that the down-regulation of GRP78 by small RNA interference improved the proliferation ability of renal cells in comparison to LPS group. The LPS-induced immune response and oxidative stress was alleviated by the depletion of GRP78. Moreover, the LPS-induced apoptosis was reduced in the GRP78 group by regulating the expression of mitochondrial apoptosis (Bcl-2, Bax) and endoplasmic reticulum (ER) stress (CHOP, caspase-12)-associated proteins. In addition, the protective role of GRP78 reduction was partly related to the balance of NF-κB/IκB. Down-regulation of GRP78 attenuated LPS-induced AKI through inhibiting immune response/oxidative stress-associated apoptosis.

BACKGROUND MicroRNAs can act as both tumor suppressor genes and oncogenes and participate in cell proliferation, metastasis, and apoptosis. Low levels of miR-577 are found in several cancers, for example, thyroid carcinoma, glioblastoma, and hepatocellular carcinoma. The aim of this study was to investigate the effect of miR-577 on breast cancer (BC). METHODS The relative level of miR-577 in 120 BC tissues and cells was detected by real-time PCR. MDA-MB-231 cells with upregulated miR-577 and MCF-7 cells with downregulated miR-577 were established. Transwell invasion assays were used to examine the invasiveness of cells. Epithelial-mesenchymal transition (EMT) markers were evaluated by immunofluorescence and Western blot. Targeted combinations of miR-577 and Rab25 were analyzed by luciferase assays. Xenograft models were used to examine the effect of miR-577 on BC metastasis. RESULTS MiR-577 expression was significantly suppressed in BC tissues. Tumor size, tumor stage, and lymphatic metastasis were attributed to miR-577 expression. Moreover, miR-577 overexpression strongly inhibited the invasiveness and EMT of BC cells in vitro. MiR-577 directly regulated Rab25 in BC. Rab25 upregulation by miR-577 decreased the levels of E-cadherin and increased the levels of Vimentin. Notably, Rab25 knockdown inhibited BC invasion; however, an increase in Rab25 counteracted the invasive effect of miR-577 in BC. CONCLUSION Results indicated that miR-577 suppressed EMT by inhibiting Rab25 expression in BC. MiR-577 and Rab25 are considered potential targets of BC treatment.

In this work, a series of novel benzyl naphthyl sulfoxides (sulfones) derived from Ex-RAD were designed and synthesized as potential radioprotective agents. Some of the compounds considerably protected HUVECs against 60Co γ-irradiation, accompanied by the absence of cytotoxicity. Compared to Ex-RAD, compound 8n not only exhibited a significant protective effect on cell survival and radiation-induced DNA damage, but also remarkably enhanced the survival (100%) of mice in 30 days after being exposed to irradiation. The results suggested that some target compounds are valuable for further research as promising radioprotectors.

Objective Sepsis, as a disease affecting the microcirculation and tissue perfusion, results in tissue hypoxia and multiple organ dysfunctions. Bone mesenchymal stem cell (BMSC)-derived extracellular vesicles (EVs) have been demonstrated to transfer trivial molecules (proteins/peptides, mRNA, microRNA and lipids) to alleviate sepsis. We sought to define the function of microRNA (miR)-17 carried in BMSC-EVs in sepsis. Methods The purity of the extracted BMSCs was identified and confirmed by detection of the surface markers by flow cytometry, followed by osteoblastic, adipogenic, and chondrocyte differentiation experiments. Subsequently, EVs were collected from the medium of BMSCs. The uptake of PKH-67-labeled BMSC-EVs or EVs carrying cy3-miR-17 by RAW264.7 cells was observed under laser confocal microscopy. Furthermore, a series of gain- and loss-of-function approaches were conducted to test the effects of LPS, miR-17 and BRD4 on the inflammatory factors (IL-1β, IL-6 and TNF-α), number of M1 macrophages and M2 macrophages, inflammatory-related signal pathway factors (EZH2, c-MYC and TRAIL), macrophage proliferation, and apoptosis in sepsis. The survival rates were measured in vivo. Results BMSC-EVs was internalized by the RAW264.7 cells. BDR4 was verified as a target of miR-17, while the expression pattern of miR-17 was upregulated in BMSC-EVs. MiR-17 carried by BMSC-EVs inhibited LPS-induced inflammation and apoptosis of RAW264.7 cells, but improved the viability of RAW264.7 cells. Next, in vitro experiments supported that miR-17 inhibited LPS-induced inflammation in RAW264.7 cells through BRD4/EZH2/TRAIL axis. BRD4 overexpression reversed the effects of miR-17. Moreover, the therapeutic function of BMSC-EVs carried miR-17 was verified by in vivo experiments. Conclusions MiR-17 derived from BMSCs-EVs regulates BRD4-mediated EZH2/TRAIL axis to essentially inhibit LPS-induced macrophages inflammation.

BACKGROUND: The aim of this prospective randomized crossover study was to compare the short-term effects of high-flow nasal cannula (HFNC) therapy and a 45° head-up tilt to the short-term effects of conventional oxygen (O2) therapy in post-abdominal surgery patients. METHODS: A total of 18 subjects who were successfully weaned from ventilator support after abdominal surgery were included in the study. The subjects were randomly assigned to 2 groups: conventional O2 was applied in group A for 15 min, and HFNC (60 L/min) was applied in group B for 15 min. A 15-min washout period with conventional O2 was performed before the interventions were switched in both groups. Heart rate, blood pressure, breathing frequency, ratio of arterial partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FIO2), and subject-reported comfort scores were recorded. Changes in end-expiratory lung impedance (EELI) were calculated with electrical impedance tomography. RESULTS: Results are presented as the percent change in lung volume compared to baseline during volume-controlled continuous mandatory ventilation before extubation. HFNC improved EELI in both the ventral (conventional O2 vs HFNC, −48.2% ± 41.0 vs −30.0% ± 40.3, P CONCLUSIONS: In post-abdominal surgery subjects who had been extubated, HFNC improved lung volume and patient comfort. A head-up tilt position introduced a heterogeneous increase in EELI in the dorsal regions of the lungs. HFNC therapy may be beneficial in this patient group. (ChiCTR1900020886, http://chictr.org.cn)