Different responses of marine microalgae Phaeodactylum tricornutum upon exposures to WAF and CEWAF of crude oil: A case study coupled with stable isotopic signatures.

Increasing use of chemical dispersants for oil spills highlights the need to understand their adverse effects on marine microalgae and nutrient assimilation because the toxic components of crude oil can be more bioavailable. We employed the crude oil water-accommodated fraction (WAF) and chemically enhanced WAF (CEWAF) to compare different responses in marine microalgae (Phaeodactylum tricornutum) coupled with stable isotopic signatures. The concentration and proportion of high-molecular-weight polycyclic aromatic hydrocarbons (HMW PAHs), which are key toxic components in crude oil, increased after dispersant addition. CEWAF exposure caused higher percent growth inhibition and a lower chlorophyll-a level of microalgae than those after WAF exposure. Compared with WAF exposure, CEWAF led to an enhancement in the self-defense mechanism of P. tricornutum, accompanied by an increased content of extracellular polymeric substances. 13C-depletion and carbon assimilation were altered in P. tricornutum, suggesting more HMW PAHs could be utilized as carbon sources by microalgae under CEWAF. CEWAF had no significant effects on the isotopic fractionation or assimilation of nitrogen in P. tricornutum. Our study unveiled the impact on the growth, physiological response, and nutrient assimilation of microalgae upon WAF and CEWAF exposures. Our data provide new insights into the ecological effects of dispersant applications for coastal oil spills.

Rigorous Assessment of Guidelines on COVID-19-Related Thrombotic or Thromboembolic Disease: Implications for Clinical Practice of Prevention, Diagnosis, and Treatment.

PURPOSE: Severe COVID-19 patients were prone to develop venous thromboembolism. Unfortunately, to date, there is no evidence of any effective medications for thromboembolism in COVID-19. The management of the disease relies on symptomatic and supportive treatments, giving rise to a variety of guidelines. However, the quality of methodology and clinical recommendations remains unknown. MATERIALS AND METHODS: We searched Medline, Cochrane Library, Web of Science, websites of international organizations and medical societies, and gray literature databases. Four well-trained appraisers independently evaluated the quality of eligible guidelines and extracted recommendations using well-recognized guideline appraisal tools. Furthermore, recommendations were extracted and reclassified according to a composite grading system. RESULTS: The search identified 23 guidelines that offered 108 recommendations. Guidelines scored average on AGREE II criteria, with Scope and Purpose and Clarity of Presentation highest. Only five (22%) guidelines provided high-quality recommendations. The existed clinical recommendations were inconsistent in terms of prophylaxis, diagnosis, and treatment of thromboembolic disease to some extent. CONCLUSION: Current guidelines for COVID-19 thromboembolism are generally of low quality, and clinical recommendations on thromboembolism are principally supported by insufficient evidence. There is still an urgent need for more well-designed clinical trials as evidence to prevent adverse events and improve prognosis during COVID-19 treatment.

Self-expanding covered metallic stents as a transition to silicone stent implantation in management of severe post-tuberculosis bronchial stenosis.

BACKGROUND AND AIMS: Post-tuberculosis bronchial stenosis (PTBS) is one of the most common complications of tracheobronchial tuberculosis. Silicone stent serves as a major treatment for maintaining airway patency. However, silicone stent placement remains a large challenge in patients with severe cicatricial PTBS. Our objective was to evaluate the efficacy and safety of covered, self-expanding, metallic stents (SEMSs) as a transition to silicone stent implantation for treating severe PTBS. METHODS: We retrospectively reviewed the data of patients with severe PTBS who received airway stenting in the First Affiliated Hospital of Guangdong Medical University between September 2015 and May 2019. The types of the stent, intervention procedures, bronchoscopic findings, clinical outcomes and related complications were collected and analyzed. RESULTS: Fifty-eight cases with severe PTBS were included in this study. Thirteen (22.4%) of the patients received bronchial silicone stent implantation immediately after dilations. For the remaining 45 (77.6%) patients, silicone stents could not be deployed after dilations and SEMSs implantation was implemented as a bridge to silicone stenting. The SEMSs were placed for an interval of 28.4 ± 11.1 days. All of the silicone stents were inserted successfully following the removal of SEMSs. No SEMS-related complication occurred. The subgroup analysis showed that patients who received transitional SEMSs had less luminal caliber but fewer transbronchial dilations before silicone stent implantation (p < 0.05). CONCLUSION: Covered SEMS placement as a transition to silicone stenting could serve as a feasible procedure to reduce complications and improve the success rate of silicone stent implantation in patients with severe PTBS.The reviews of this paper are available via the supplemental material section.

Homoharringtonine regulates the alternative splicing of Bcl-x and caspase 9 through a protein phosphatase 1-dependent mechanism.

BACKGROUND: Homoharringtonine (HHT) is a natural alkaloid with potent antitumor activity, but its precise mechanism of action is still poorly understood. METHODS: We examined the effect of HHT on alternative splicing of Bcl-x and Caspase 9 in various cells using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The mechanism of HHT-affected alternative splicing in these cells was investigated by treatment with protein phosphatase inhibitors and overexpression of a protein phosphatase. RESULTS: Treatment with HHT downregulated the levels of anti-apoptotic Bcl-xL and Caspase 9b mRNA with a concomitant increase in the mRNA levels of pro-apoptotic Bcl-xS and Caspase 9a in a dose- and time-dependent manner. Calyculin A, an inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), significantly inhibited the effects of HHT on the alternative splicing of Bcl-x and Caspase 9, in contrast to okadaic acid, a specific inhibitor of PP2A. Overexpression of PP1 resulted in a decrease in the ratio of Bcl-xL/xS and an increase in the ratio of Caspase 9a/9b. Moreover, the effects of HHT on Bcl-x and Caspase 9 splicing were enhanced in response to PP1 overexpression. These results suggest that HHT-induced alternative splicing of Bcl-x and Caspase 9 is dependent on PP1 activation. In addition, overexpression of PP1 could induce apoptosis and sensitize MCF7 cells to apoptosis induced by HHT. CONCLUSION: Homoharringtonine regulates the alternative splicing of Bcl-x and Caspase 9 through a PP1-dependent mechanism. Our study reveals a novel mechanism underlying the antitumor activities of HHT.

Gigantol inhibits Wnt/ß-catenin signaling and exhibits anticancer activity in breast cancer cells.

BACKGROUND: Gigantol is a bibenzyl compound derived from several medicinal orchids. This biologically active compound has been shown to have promising therapeutic potential against cancer cells, but its mechanism of action remains unclear. METHODS: The inhibitory effect of gigantol on Wnt/ß-catenin signaling was evaluated with the SuperTOPFlash reporter system. The levels of phosphorylated low-density lipoprotein receptor related protein 6 (LRP6), total LRP6 and cytosolic ß-catenin were determined by Western blot analysis. The expression of Wnt target genes was analyzed using real-time PCR. Cell viability was measured with a MTT assay. The effect of gigantol on cell migration was examined using scratch wound-healing and transwell migration assays. RESULTS: Gigantol decreased the level of phosphorylated LRP6 and cytosolic ß-catenin in HEK293 cells. In breast cancer MDA-MB-231 and MDA-MB-468 cells, treatment with gigantol reduced the level of phosphorylated LRP6, total LRP6 and cytosolic ß-catenin in a dose-dependent manner, resulting in a decrease in the expression of Wnt target genes Axin2 and Survivin. We further demonstrated that gigantol suppressed the viability and migratory capacity of breast cancer cells. CONCLUSION: Gigantol is a novel inhibitor of the Wnt/ß-catenin pathway. It inhibits Wnt/ß-catenin signaling through downregulation of phosphorylated LRP6 and cytosolic ß-catenin in breast cancer cells.

Efficacies and adverse reactions of modified vitamin supplement programs before pemetrexed chemotherapy as a second-line treatment against epidermal growth factor receptor (EGFR) mutant wild-type lung adenocarcinoma.

OBJECTIVE: This study aims to observe the efficacies and adverse reactions of modified vitamin programs before pemetrexed chemotherapy (second-line treatment) against epidermal growth factor receptor (EGFR) mutant wild-type lung adenocarcinoma. METHODS: 477 patients with IIIB, phase IV glomerular filtration rate (GFR) mutant-negative lung adenocarcinomas and performed pemetrexed chemotherapy were collected and divided into group A (167 cases, with modified program) and group B (310 cases, with traditional program). The modified program was: orally administrated 400 µg folic acid once per day and 1 day before the first-round pemetrexed chemotherapy, until the 21st day of the final administration of pemetrexed, and intramuscularly injected 500 µg vitamin B12 1 day before the first-round pemetrexed chemotherapy, and injected once 1 day before every round pemetrexed treatment. RESULTS: Comparison between group A and group B: mean chemotherapy cycles (4.08 vs 3.98); effectiveness rate (22.16% vs 22.90%); disease control rate (56.51% vs 55.00%); without significant difference (P > 0.05). Two groups currently all reached the median overall survival (OS). The median progression-free survival (PFS): 4.2 vs 4.1 months; OS: 12.9 vs 13.2 months, without statistical difference (P > 0.05). Such side effects between the two groups as leukopenia, neutropenia, thrombocytopenia, anemia, nausea, vomiting, diarrhea, fatigue, creatinine increasing, alanine transaminase (ALT) increasing, stomatitis, peripheral neuropathy, alopecia and rash had no significant difference (P > 0.05). CONCLUSIONS: The modified vitamin supportive treatment could ensure the efficacy, significantly simplify, facilitate the clinical application, and increase the associated toxicities, indicating that the pemetrexed-based chemotherapy did not need to be delayed because applying the vitamin supportive treatment.

[Effectiveness of cultured Cordyceps sinensis combined with glucocorticosteroid on pulmonary fibrosis induced by bleomycin in rats].

OBJECTIVE: To study the treatment effects of cultured Cordyceps sinensis combined with glucocorticosteroid on experimental pulmonary fibrosis in rats induced by bleomycin. METHOD: Fifty rats were randomly divided into five groups, including control group, model group, cultured C. sinensis groups, prednisone group, cultured C. sinensis combined with prednisone group. On experimental day 0, the rats were respectively intratracheally instilled with bleomycin, and rats in the control group and model group with the same volume of normal saline. One day after the injection, cultured C. sinensis and glucocorticosteroid was respectively given to rats daily by gastric gavage, while the same volume of normal saline was given to those in the control group and model group. On 28th d, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. Histological changes of the lungs were evaluated by HE stain, Masson's trichrome stain. Collagen content of the lung tissue was assessed by hydroxyprolin concentration. Lung expression of CTGF protein was assessed by immunohistochemistry. The level of TGF-beta1 protein was measured by ELISA. RESULT: Compared to model group, pulmonary fibrosis were alleviated in cultured C. sinensis and prednisone group, and CTGF expression, Hydroxyproline concentrations and protein TGF-beta1 were decreased. The combination effect of C. sinensis and prednisone group is augmented compared with using C. sinensis or prednisone group alone. CONCLUSION: The cultured C. sinensis and prednisone alleviates pulmonary fibrosis, and the combination use of both drugs has synergia effects in anti-fibrous degeneration.

[Study on the extraction of breviscapine from Erigeron breviscapus with ultrasonic wave technology optimized by central composite design-response surface method].

OBJECTIVE: To evaluate the effectiveness of ultrasound-assisted extraction and establish the optimized extraction conditions of breviscapine from Erigeron breviscapus. METHODS: On the basis of the single factor and according to the central composite design principles (CCD), the response surface method (RSM) with 3 factors and 3 levels was adopted and the independent variables were ultrasonic wave extracting time, ethanol concentration, and the ratio of solvent volume to Erigeron breviscapus mass, breviscapine extraction yield determinated by HPLC was used as response value. RESULTS: Ultrasonic wave extracting time of 24.5 min, ethanol concentration of 74.7% and the ratio of solvent volume to Erigeron breviscapus mass of 19.8 (mL/g) were selected as optimum conditions. Regression coefficients of binomial fitting complex model was 0. 9549 and the predicted breviscapine extraction yield was 0.641%, while the actual extraction yield was 0.632% (n = 5), with relative error of -1.14%. CONCLUSION: This study confirms the efficiency of ultrasound-assisted extraction as a simple, inexpensive and effective method to improve the extraction of breviscapine from Erigeron breviscapus. The observed and predicted values are close to each other, which proves that the optimization of supersonic extraction process of breviscapine from Erigeron breviscapus by CCD-RSM is reasonable and successful.

[Pharmacological effects of Bailing capsule and its application in lung disease research].

Cordyceps sinensis is a medicinal fungus of Traditional Chinese Medicine. There are a wide range of reported uses of Cordycep sinensis in the literature. However, the production of Cordyceps sinensis is so limited that can not be widely used. Cultured Cordyceps sinensis (Bailing Capsule) and natural Cordyceps sinensis have similar chemical composition. Bailing Capsule possesses anti-inflammatory, anti-hypoxia, anti-tumor effect function and regulating the endocrine system, enhanced immune function, which has a protective effect on the kidney, lung, liver and other organs. Recently, Bailing capsule has some beneficial effects on pulmonary diseases, such as COPD, Pulmonary fibrosis, Asthma, which have been gradually applied to the clinical.