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ministration. Conclusion COE can significantly promote apoptosis of human gastric cancer cells, which can be achieved by inhibiting PHB expression, thus altering the structure and function of mitochondria and activating the mitochondria apoptosis pathway. The antitumor effect of COE has also been proved in vivo.Chronic kidney disease (CKD) is a common progressive disease that is typically characterized by the permanent loss of nephrons and an eventual decline in glomerular filtration rate. CKD increases mortality and has a significant impact on the quality of life and the economy, which is becoming a major public health issue worldwide. Since current conventional-medicine treatment options for CKD are not satisfactory, many patients seek complementary and alternative medicine treatments including Traditional Chinese Medicine. Herbal medicine is often used to relieve symptoms of renal diseases in the clinic. The kidney is abundant in the number of mitochondria, which provide enough energy for renal function and metabolism. In recent years, a vital role for mitochondrial dysfunction has been suggested in CKD. Mitochondria have become a new target for the treatment of diseases. A growing number of studies have demonstrated herbal medicine could restore mitochondrial function and alleviate renal injury both in vivo and in vitro. In this review, we sum up the therapeutic effect of herbal medicine in CKD via targeting mitochondrial function. This implies future strategies in preventing CKD.After initial treatment, maintenance therapy is now commonly used in mCRC patients, which can help patients live longer, have lower side effects, and higher quality of life. The maintenance treatment may include chemotherapy, targeted therapy, or combined with chemotherapy and targeted therapy. But the evidence of cetuximab maintenance is still scant. read more Methods We collected real-world data of wild-type RAS unresectable mCRC patients who were treated with cetuximab-based chemotherapy as the first-line therapy between January 2013 and December 2018 at the Zhejiang Cancer Hospital (Hangzhou, China). Results A total of 177 patients were ultimately included in the study, and 107 patients had progression information in medical records; all patients had survival data. The median OS was 40.9 ms, ORR was 14.7%, and DCR was 73.5%. The subgroup analysis showed that the mOS was better in maintenance patients than in non-maintenance patients (47.1 vs. 28.6 ms, p = 0.001), patients with primary tumor resection had better mOS tumor site and primary tumor resection also affect the OS, primary tumor resection better than did not (not reach the end vs. 35.7 ms, p = 0.048), left side better than right side (47.1 vs. 16.6 ms, p less then 0.001), which is consistent with the literature report. There was no statistical difference in other subgroups. Conclusion For patients with all RAS wild-type and initially unresectable mCRC who experienced standard first-line cetuximab-based treatment and maintenance treatment that contained cetuximab can significantly improve the mPFS and mOS, and the observed toxicity was mostly mild too. So, we consider that cetuximab can be an effective and safety maintenance drug in mCRC patients.Females are generally more affected by autoimmune diseases, a fact that underlines the relationship with pregnancy and the safety of anti-rheumatic drugs in pregnancy and lactation. Biologic therapies are increasingly prescribed to treat and maintain remission in a significant number of systemic autoimmune rheumatic diseases. The experience with the use of biologics during gestation is extremely lacking because of the observational nature of the available studies and the difficulty in designing proper clinical trials in pregnancy. Among the studied biologics, more information was published on TNFα inhibitors and, in particular, on their potential passage through the placenta and impact on the fetus. Currently, a fragment of anti-TNFα monoclonal IgG, certolizumab pegol, is considered safe with almost no placental transfer. Subsequent observations are suggesting a comparable safety for the soluble TNFα receptor etanercept. Another biologic, eculizumab, the anti-C5a antibody used to treat complement-mediated microangiopathies, is also considered safe due to the unique engineered IgG2/4κ formulation that limits its passage through the placental barrier. Still, long-term data about children born to women treated with biologics in pregnancy are not attainable. Data on breastfeeding are currently available for several biologics. This article reviews the literature available about which drugs are considered safe during pregnancy and lactation, which are not, and on future prospects.Background Chemotherapy is suspected to be a risk factor for stroke in patients with cancer, athough the results from large-scale studies are controversial. Few strategies are available for reducing the stroke-related risks. Methods We analyzed stroke incidence rates in Taiwan's Longitudinal Health Insurance database 2000 (LHID2000) for patients aged ≥20 years with newly-diagnosed cancer between Jan 1, 2000 and Dec 31, 2006, who did or did not receive chemotherapy. Moreover, we compared stroke incidence rates among chemotherapy users who did or did not use traditional Chinese medicine. All study participants were followed-up for 5 years or until they had a stroke. Results In adjusted Kaplan-Meier analysis, the incidence of stroke was higher within the first year of cancer diagnosis among chemotherapy recipients compared with those who did not receive chemotherapy (31.1 vs. 9.75; adjusted subdistribution hazard ratio [sHR] 2.21; 95% confidence interval [CI], 1.52-3.20; p less then 0.001). This between-group difference persisted at 4 years of follow-up (13.6 vs. 5.42; adjusted sHR 1.94; 95% CI, 1.53-2.46; p less then 0.001). Similarly, the 5-year incidence rate of stroke was significantly lower among chemotherapy recipients using TCM vs. non-TCM users (0.19 vs. 0.46; adjusted sHR 0.45; 95% CI, 0.26-0.79; p less then 0.001), as was the mortality rate (adjusted sHR 0.55; 95% CI, 0.44-0.68; p less then 0.001). Conclusion These Taiwanese data suggest that chemotherapy is a risk factor for stroke and that the use of TCM can significantly mitigate this risk. TCM also appears to reduce the mortality risk associated with chemotherapy.Background Salvianolic acid A (Sal A), a natural polyphenolic compound extracted from Radix Salvia miltiorrhiza (Danshen), exhibits exceptional pharmacological activities against cardiovascular diseases. While a few studies have reported anti-obesity properties of Sal A, the underlying mechanisms are largely unknown. Given the prevalence of obesity and promising potential of browning of white adipose tissue to combat obesity, recent research has focused on herbal ingredients that may promote browning and increase energy expenditure. Purpose The present study was designed to investigate the protective antiobesity mechanisms of Sal A, in part through white adipose browning. Methods Both high-fat diet (HFD)-induced obese (DIO) male mice model and fully differentiated C3H10T1/2 adipocytes from mouse embryo fibroblasts were employed in this study. Sal A (20 and 40 mg/kg) was administrated to DIO mice by intraperitoneal injection for 13-weeks. Molecular mechanisms mediating effects of Sal A were evaluated. Resluts Sal A treatment significantly attenuated HFD-induced weight gain and lipid accumulation in epididymal fat pad. Uncoupling protein 1 (UCP-1), a specialized thermogenic protein and marker for white adipocyte browning, was significantly induced by Sal A treatment in both white adipose tissues and cultured adipocytes. Further mechanistic investigations revealed that Sal A robustly reversed HFD-decreased AMP-activated protein kinase (AMPK) phosphorylation and sirtuin 1 (SIRT1) expression in mice. Genetically silencing either AMPK or SIRT1 using siRNA abolished UCP-1 upregulation by Sal A. AMPK silencing significantly blocked Sal A-increased SIRT1 expression, while SIRT1 silencing did not affect Sal A-upregulated phosphorylated-AMPK. These findings indicate that AMPK was involved in Sal A-increased SIRT1. Conclusion Sal A increases white adipose tissue browning in HFD-fed male mice and in cultured adipocytes. Thus, Sal is a potential natural therapeutic compound for treating and/or preventing obesity.Acute lymphoblastic leukemia (ALL) is an aggressive malignancy. Adults with ALL have more than 50% relapse rates. We have previously validated that overexpression of nucleophosmin (NPM) is involved in the multidrug resistance (MDR) development during ALL; and a synthetically engineered recombinant NPM binding protein (NPMBP) has been developed in our group; NPMBP and doxorubicin (DOX) can be conjugated in a nanoparticle-based drug delivery system named DOX-PMs-NPMBP to counteract MDR during ALL. Here, we evaluated the antileukemia potential of DOX-PMs-NPMBP in resistant ALL cells. This study demonstrates that DOX-PMs-NPMBP significantly enhances chemosensitivity to DOX in ALL cells. Despite at variable concentrations, both resistant and primary ALL cells from relapsed patients were sensitive to DOX-PMs-NPMBP. In detail, the half maximal inhibitory concentration (IC50) values of DOX-PMs-NPMBP were between 1.6- and 7.0-fold lower than those of DOX in cell lines and primary ALL cells, respectively; and apoptotic cells ratio was over 2-fold higher in DOX-PMs-NPMBP than DOX. Mechanistically, p53-driven apoptosis induction and cell cycle arrest played essential role in DOX-PMs-NPMBP-induced anti-leukemia effects. Moreover, DOX-PMs-NPMBP significantly inhibited tumor growth and prolonged mouse survival of ALL xenograft models; and no systemic toxicity occurrence was observed after treatment during follow-up. In conclusion, these data indicate that DOX-PMs-NPMBP may significantly exert growth inhibition and apoptosis induction, and markedly improve DOX antileukemia activity in resistant ALL cells. This novel drug delivery system may be valuable to develop as a new therapeutic strategy against multidrug resistant ALL.Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2), a β-coronavirus, is the cause of the recently emerged pandemic and worldwide outbreak of respiratory disease. Researchers exchange information on COVID-19 to enable collaborative searches. Although there is as yet no effective antiviral agent, like tamiflu against influenza, to block SARS-CoV-2 infection to its host cells, various candidates to mitigate or treat the disease are currently being investigated. Several drugs are being screened for the ability to block virus entry on cell surfaces and/or block intracellular replication in host cells. Vaccine development is being pursued, invoking a better elucidation of the life cycle of the virus. SARS-CoV-2 recognizes O-acetylated neuraminic acids and also several membrane proteins, such as ACE2, as the result of evolutionary switches of O-Ac SA recognition specificities. To provide information related to the current development of possible anti-SARS-COV-2 viral agents, the current review deals with the known inhibitory compounds with low molecular weight. The molecules are mainly derived from natural products of plant sources by screening or chemical synthesis via molecular simulations. Artificial intelligence-based computational simulation for drug designation and large-scale inhibitor screening have recently been performed. Structure-activity relationship of the anti-SARS-CoV-2 natural compounds is discussed.
My Website: https://www.selleckchem.com/products/alofanib-rpt835.html
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