Synthesis and Antibacterial Evaluation of Novel Vancomycin Derivatives Containing Quaternary Ammonium Moieties

A series of novel vancomycin analogues with quaternary ammonium moieties have been designed and synthesized for fighting with clinically isolated drug-resistant bacteria. Partial target molecules exhibited potent activity against the tested strains. Among all of the compounds, a triazole quaternary ammonium vancomycin (QAV) derivative QAV-a1 exerted the best antibacterial activities. QAV-a1 was found to be 4- to 32-fold more efficacious than vancomycin against MRSA. Meanwhile, QAV-a1 showed a good pharmacokinetic profile with a half-life of 5.19 ± 0.10 h, which is longer than that of vancomycin (4.3 ± 1.9 h). These results provided guidance for the further exploitation of vancomycin derivatives against drug-resistant bacteria

Table_2_A Novel Stool Methylation Test for the Non-Invasive Screening of Gastric and Colorectal Cancer.xlsx

BackgroundBecause of poor compliance or low sensitivity, existing diagnostic approaches are unable to provide an efficient diagnosis of patients with gastric and colorectal cancer. Here, we developed the ColoCaller test, which simultaneously detects the methylation status of the SDC2, TFPI2, WIF1, and NDRG4 genes in stool DNA, to optimize the screening of gastric and colorectal cancer in high-risk populations.MethodsA total of 217 stool samples from patients with gastrointestinal cancer and from patients with negative endoscopy were prospectively collected, complete with preoperative and postoperative clinical data from patients. The methylation of these samples was detected using ColoCaller, which was designed by selecting CpGs with a two-step screening strategy, and was interpreted using a prediction model built using libSVM to evaluate its clinical value for gastric and colorectal cancer screening.ResultsCompared to pathological diagnosis, the sensitivity and specificity of the ColoCaller test in 217 stool DNA samples were 95.56% and 91.86%, respectively, for colorectal cancer, and 67.5% and 97.81%, respectively, for gastric cancer. The detection limit was as low as 1% in 8 ng of DNA.ConclusionIn this study, we developed and established a new test, ColoCaller, which can be used as a screening tool or as an auxiliary diagnostic approach in high-risk populations with gastric and colorectal cancer to promote timely diagnosis and treatment.</p

Image_1_A Novel Stool Methylation Test for the Non-Invasive Screening of Gastric and Colorectal Cancer.tif

BackgroundBecause of poor compliance or low sensitivity, existing diagnostic approaches are unable to provide an efficient diagnosis of patients with gastric and colorectal cancer. Here, we developed the ColoCaller test, which simultaneously detects the methylation status of the SDC2, TFPI2, WIF1, and NDRG4 genes in stool DNA, to optimize the screening of gastric and colorectal cancer in high-risk populations.MethodsA total of 217 stool samples from patients with gastrointestinal cancer and from patients with negative endoscopy were prospectively collected, complete with preoperative and postoperative clinical data from patients. The methylation of these samples was detected using ColoCaller, which was designed by selecting CpGs with a two-step screening strategy, and was interpreted using a prediction model built using libSVM to evaluate its clinical value for gastric and colorectal cancer screening.ResultsCompared to pathological diagnosis, the sensitivity and specificity of the ColoCaller test in 217 stool DNA samples were 95.56% and 91.86%, respectively, for colorectal cancer, and 67.5% and 97.81%, respectively, for gastric cancer. The detection limit was as low as 1% in 8 ng of DNA.ConclusionIn this study, we developed and established a new test, ColoCaller, which can be used as a screening tool or as an auxiliary diagnostic approach in high-risk populations with gastric and colorectal cancer to promote timely diagnosis and treatment.</p

Image_2_A Novel Stool Methylation Test for the Non-Invasive Screening of Gastric and Colorectal Cancer.tif

BackgroundBecause of poor compliance or low sensitivity, existing diagnostic approaches are unable to provide an efficient diagnosis of patients with gastric and colorectal cancer. Here, we developed the ColoCaller test, which simultaneously detects the methylation status of the SDC2, TFPI2, WIF1, and NDRG4 genes in stool DNA, to optimize the screening of gastric and colorectal cancer in high-risk populations.MethodsA total of 217 stool samples from patients with gastrointestinal cancer and from patients with negative endoscopy were prospectively collected, complete with preoperative and postoperative clinical data from patients. The methylation of these samples was detected using ColoCaller, which was designed by selecting CpGs with a two-step screening strategy, and was interpreted using a prediction model built using libSVM to evaluate its clinical value for gastric and colorectal cancer screening.ResultsCompared to pathological diagnosis, the sensitivity and specificity of the ColoCaller test in 217 stool DNA samples were 95.56% and 91.86%, respectively, for colorectal cancer, and 67.5% and 97.81%, respectively, for gastric cancer. The detection limit was as low as 1% in 8 ng of DNA.ConclusionIn this study, we developed and established a new test, ColoCaller, which can be used as a screening tool or as an auxiliary diagnostic approach in high-risk populations with gastric and colorectal cancer to promote timely diagnosis and treatment.</p

Data_Sheet_1_Effect of Electro-Acupuncture at ST36 and SP6 on the cAMP -CREB Pathway and mRNA Expression Profile in the Brainstem of Morphine Tolerant Mice.ZIP

Undoubtedly, opioid drugs have been the most popular treatment for refractory pain since found, such as morphine. However, tolerance to the analgesic effects caused by repeated use is inevitable, which greatly limits the clinical application of these drugs. Nowadays, it has become the focus of the world that further development of non-opioid-based treatment along with efficient strategies to circumvent opioid tolerance are urgently needed clinically. Fortunately, electro-acupuncture (EA) provides an alternative to pharmaceutic treatment, remaining its potential mechanisms unclear although. This study was aimed to observe the effects of EA on morphine-induced tolerance in mice and discover its underlying mechanism. Tail-flick assay and hot-plate test were conducted to assess the development of tolerance to morphine-induced analgesia effect. As a result of repeated administration scheme (10 mg/kg, twice per day, for 7 days), approximately a two-fold increase was observed in the effective dose of 50% (ED50) of morphine-induced antinociceptive effect. Interestingly, by EA treatment (2/100Hz, 0.5, 1.0, and 1.5 mA, 30 min/day for 7 days) at the acupoints Zusanli (ST36) and Sanyinjiao (SP6), morphine ED50 curves was remarkably leftward shifted on day 8. In addition, the RNA sequencing strategy was used to reveal the potential mechanisms. Due to the well described relevance of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), extracellular regulated protein kinases (ERK), and cAMP response element-binding (CREB) in brainstem (BS) to analgesia tolerance, the cAMP-PKA/ERK-CREB signaling was deeply concerned in this study. Based upon Enzyme-Linked Immunosorbent Assay, the up-regulation of the cAMP level was observed, whereas reversed with EA treatment. Similarly, western blot revealed the phosphorylation levels of PKA, ERK, and CREB were up-regulated in morphine tolerant mice, whereas the EA group showed a significantly reduced expression level instead. This study observed an attenuating effect of the EA at ST36 and SP6 on morphine tolerance in mice, and suggested several potential biological targets by RNA-seq, which include the cAMP-PKA/ERK-CREB signaling pathway, strongly supporting a useful treatment for combatting the opioid epidemic, and opioid-tolerant patients.</p

Additional file 1 of A novel method for early detection of colorectal cancer based on detection of methylation of two fragments of syndecan-2 (SDC2) in stool DNA

Additional file 1. Table S1. Potentially interfering substances tested in this study. Table S2. The interpretation criteria of test results. Table S3. Stool DNA test for methylated SDC2 in different studies

Image_4_A Novel Stool Methylation Test for the Non-Invasive Screening of Gastric and Colorectal Cancer.tif

BackgroundBecause of poor compliance or low sensitivity, existing diagnostic approaches are unable to provide an efficient diagnosis of patients with gastric and colorectal cancer. Here, we developed the ColoCaller test, which simultaneously detects the methylation status of the SDC2, TFPI2, WIF1, and NDRG4 genes in stool DNA, to optimize the screening of gastric and colorectal cancer in high-risk populations.MethodsA total of 217 stool samples from patients with gastrointestinal cancer and from patients with negative endoscopy were prospectively collected, complete with preoperative and postoperative clinical data from patients. The methylation of these samples was detected using ColoCaller, which was designed by selecting CpGs with a two-step screening strategy, and was interpreted using a prediction model built using libSVM to evaluate its clinical value for gastric and colorectal cancer screening.ResultsCompared to pathological diagnosis, the sensitivity and specificity of the ColoCaller test in 217 stool DNA samples were 95.56% and 91.86%, respectively, for colorectal cancer, and 67.5% and 97.81%, respectively, for gastric cancer. The detection limit was as low as 1% in 8 ng of DNA.ConclusionIn this study, we developed and established a new test, ColoCaller, which can be used as a screening tool or as an auxiliary diagnostic approach in high-risk populations with gastric and colorectal cancer to promote timely diagnosis and treatment.</p

Table_3_A Novel Stool Methylation Test for the Non-Invasive Screening of Gastric and Colorectal Cancer.xlsx

BackgroundBecause of poor compliance or low sensitivity, existing diagnostic approaches are unable to provide an efficient diagnosis of patients with gastric and colorectal cancer. Here, we developed the ColoCaller test, which simultaneously detects the methylation status of the SDC2, TFPI2, WIF1, and NDRG4 genes in stool DNA, to optimize the screening of gastric and colorectal cancer in high-risk populations.MethodsA total of 217 stool samples from patients with gastrointestinal cancer and from patients with negative endoscopy were prospectively collected, complete with preoperative and postoperative clinical data from patients. The methylation of these samples was detected using ColoCaller, which was designed by selecting CpGs with a two-step screening strategy, and was interpreted using a prediction model built using libSVM to evaluate its clinical value for gastric and colorectal cancer screening.ResultsCompared to pathological diagnosis, the sensitivity and specificity of the ColoCaller test in 217 stool DNA samples were 95.56% and 91.86%, respectively, for colorectal cancer, and 67.5% and 97.81%, respectively, for gastric cancer. The detection limit was as low as 1% in 8 ng of DNA.ConclusionIn this study, we developed and established a new test, ColoCaller, which can be used as a screening tool or as an auxiliary diagnostic approach in high-risk populations with gastric and colorectal cancer to promote timely diagnosis and treatment.</p

Table_4_A Novel Stool Methylation Test for the Non-Invasive Screening of Gastric and Colorectal Cancer.xlsx

BackgroundBecause of poor compliance or low sensitivity, existing diagnostic approaches are unable to provide an efficient diagnosis of patients with gastric and colorectal cancer. Here, we developed the ColoCaller test, which simultaneously detects the methylation status of the SDC2, TFPI2, WIF1, and NDRG4 genes in stool DNA, to optimize the screening of gastric and colorectal cancer in high-risk populations.MethodsA total of 217 stool samples from patients with gastrointestinal cancer and from patients with negative endoscopy were prospectively collected, complete with preoperative and postoperative clinical data from patients. The methylation of these samples was detected using ColoCaller, which was designed by selecting CpGs with a two-step screening strategy, and was interpreted using a prediction model built using libSVM to evaluate its clinical value for gastric and colorectal cancer screening.ResultsCompared to pathological diagnosis, the sensitivity and specificity of the ColoCaller test in 217 stool DNA samples were 95.56% and 91.86%, respectively, for colorectal cancer, and 67.5% and 97.81%, respectively, for gastric cancer. The detection limit was as low as 1% in 8 ng of DNA.ConclusionIn this study, we developed and established a new test, ColoCaller, which can be used as a screening tool or as an auxiliary diagnostic approach in high-risk populations with gastric and colorectal cancer to promote timely diagnosis and treatment.</p

Table_1_A Novel Stool Methylation Test for the Non-Invasive Screening of Gastric and Colorectal Cancer.xlsx

BackgroundBecause of poor compliance or low sensitivity, existing diagnostic approaches are unable to provide an efficient diagnosis of patients with gastric and colorectal cancer. Here, we developed the ColoCaller test, which simultaneously detects the methylation status of the SDC2, TFPI2, WIF1, and NDRG4 genes in stool DNA, to optimize the screening of gastric and colorectal cancer in high-risk populations.MethodsA total of 217 stool samples from patients with gastrointestinal cancer and from patients with negative endoscopy were prospectively collected, complete with preoperative and postoperative clinical data from patients. The methylation of these samples was detected using ColoCaller, which was designed by selecting CpGs with a two-step screening strategy, and was interpreted using a prediction model built using libSVM to evaluate its clinical value for gastric and colorectal cancer screening.ResultsCompared to pathological diagnosis, the sensitivity and specificity of the ColoCaller test in 217 stool DNA samples were 95.56% and 91.86%, respectively, for colorectal cancer, and 67.5% and 97.81%, respectively, for gastric cancer. The detection limit was as low as 1% in 8 ng of DNA.ConclusionIn this study, we developed and established a new test, ColoCaller, which can be used as a screening tool or as an auxiliary diagnostic approach in high-risk populations with gastric and colorectal cancer to promote timely diagnosis and treatment.</p