Repurposing Astragalus Polysaccharide PG2 for Inhibiting ACE2 and SARS-CoV-2 Spike Syncytial Formation and Anti-Inflammatory Effects.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global public health. In an effort to develop novel anti-coronavirus therapeutics and achieve prophylactics, we used gene set enrichment analysis (GSEA) for drug screening and identified that Astragalus polysaccharide (PG2), a mixture of polysaccharides purified from Astragalus membranaceus, could effectively reverse COVID-19 signature genes. Further biological assays revealed that PG2 could prevent the fusion of BHK21-expressing wild-type (WT) viral spike (S) protein and Calu-3-expressing ACE2. Additionally, it specifically prevents the binding of recombinant viral S of WT, alpha, and beta strains to ACE2 receptor in our non-cell-based system. In addition, PG2 enhances let-7a, miR-146a, and miR-148b expression levels in the lung epithelial cells. These findings speculate that PG2 has the potential to reduce viral replication in lung and cytokine storm via these PG2-induced miRNAs. Furthermore, macrophage activation is one of the primary issues leading to the complicated condition of COVID-19 patients, and our results revealed that PG2 could regulate the activation of macrophages by promoting the polarization of THP-1-derived macrophages into an anti-inflammatory phenotype. In this study, PG2 stimulated M2 macrophage activation and increased the expression levels of anti-inflammatory cytokines IL-10 and IL-1RN. Additionally, PG2 was recently used to treat patients with severe COVID-19 symptoms by reducing the neutrophil-to-lymphocyte ratio (NLR). Therefore, our data suggest that PG2, a repurposed drug, possesses the potential to prevent WT SARS-CoV-2 S-mediated syncytia formation with the host cells; it also inhibits the binding of S proteins of WT, alpha, and beta strains to the recombinant ACE2 and halts severe COVID-19 development by regulating the polarization of macrophages to M2 cells.

Colorimetric detection of Al3+ ions using triazole-ether functionalized gold nanoparticles.

A sensitive, selective colorimetric Al(3+) detection method has been developed by using triazole-ether functionalized gold nanoparticles (TTP-AuNPs). Gold nanoparticles were prepared by reducing HAuCl4 with sodium borohydride in the presence of 5-(1,2-dithiolan-3-yl)-N-(prop-2-yn-1-yl)pentanamide (TP). The azide part of 2-[2-(2-azidoethoxy)ethoxy]ethanol and the acetylene part of TP were combined to form a triazole structure through a click reaction. Aggregation of TTP-AuNPs was induced immediately in the presence of Al(3+) ions, yielding a color change from red to blue. This Al(3+)-induced aggregation of TTP-AuNPs was monitored first with the naked eye and then UV-vis spectroscopy with a detection limit of 18.0 nM. The TTP-AuNPs showed excellent selectivity for Al(3+), compared to other metal ions (Ag(+), Ca(2+), Cd(2+), Co(2+), Cu(2+), Cr(3+), Fe(2+), Fe(3+), Hg(2+), Mg(2+), Mn(2+), Ni(2+), Pb(2+), and Zn(2+)). In addition, TTP-AuNPs were used to detect Al(3+) in sea water samples, with low interference.

Desirable training and roles of Japanese endoscopists towards the further penetration of endoscopic submucosal dissection in Asia.

Endoscopic submucosal dissection (ESD) was invented in Japan and is now permeating into the rest of the world. Therefore, it is necessary to elucidate the desirable ESD training by knowing the current status of ESD training in Japan. After this, we mainly discussed the following three topics: (i) requirements for preceptees to start ESD training; (ii) requirements for competent endoscopists in ESD; and (iii) requirements for preceptors in the first half of the upper gastrointestinal tract session at the Endoscopic Forum Japan 2011. Additionally, we discussed what Japanese endoscopists can do for further permeation of ESD outside Japan, especially in Asia in the second half. The session was wrapped up by the conclusions that it was absolutely necessary to establish official training courses authorized by the Japan Gastroenterological Endoscopy Society with certification for trainees and trainers and our Japanese endoscopists had a responsibility to spread ESD safely and reliably by collaborating with enthusiastic endoscopists in each country which have different backgrounds in terms of incidences and screening systems of target diseases, accessibility to endoscopy, medical economics, national characters, and so on.

Current situation of endoscopic submucosal dissection for superficial neoplasms in the upper digestive tract in East Asian countries: a questionnaire survey.

AIM: This study was carried out to understand the current practice and learning of endoscopic submucosal dissection (ESD) for superficial esophageal and gastric cancers in East Asian countries. METHODS: A questionnaire survey was used to investigate differences in upper gastrointestinal (GI) ESD among East Asian countries. RESULTS: ESD is used by many endoscopists in not only tertiary centers but also secondary care hospitals in China, Korea and Japan. By contrast, it is less used by doctors in tertiary centers in Hong Kong and Taiwan. However, the general trend appears to be the same; ESD, which is a highly advanced endoscopic technique, is being transmitted from preceptors to preceptees in tertiary centers, then from doctors in tertiary centers to experienced doctors in secondary hospitals. The speed of learning and uptake in the practice of this procedure will depend on the volume of cases. Upper GI ESD can be expected to spread at a similar rate across different districts or hospitals in East Asia because of similarities in disease prevalence. Also, endoscopists in this region can easily learn from each other by attending international conferences or visiting endoscopy units to learn the procedure. CONCLUSION: Efforts to establish a standardized protocol for ESD practice and training are important, and may help endoscopists around the world develop this technique further.

Narrowband imaging for early detection of malignant tumors and radiation effect after treatment of head and neck cancer.

OBJECTIVES: To determine the value of narrowband imaging (NBI) screening for the early detection of head and neck squamous cell carcinoma (HNSCC) in patients who have received treatment and to assess the impact of radiotherapy on detection rates. DESIGN: Cross-sectional study. SETTING: Tertiary referral center. PATIENTS: From July 1, 2007, through February 28, 2008, a total of 206 patients with HNSCC underwent rhinolarynx videoendoscopic screening performed using conventional white-light and NBI systems during their routine postoperative sessions. MAIN OUTCOME MEASURE: The rate of detecting malignant tumors, depending on the anatomical site and stage of cancer and the history of radiotherapy after primary treatment. RESULTS: We identified 68 lesions by endoscopy in conventional white-light and/or NBI mode. Of these, 62 were histopathologically confirmed to be cancerous. The rates of detecting cancerous lesions by white-light and NBI modes were 100% and 97% for oral lesions, 69% and 100% for oropharyngeal lesions (P = .02), and 39% and 100% for hypopharyngeal lesions (P = .001), respectively. No difference was found between the 2 modes with regard to the detection of visible T1 to T4 tumors. However, NBI mode was significantly better than white-light mode for the detection of carcinoma in situ (P < .001). CONCLUSION: We found that NBI-assisted endoscopy is highly useful for the detection of precancerous lesions in the oropharyngeal and hypopharyngeal mucosa and is not affected by a history of radiotherapy in patients with HNSCC.

FibroQ: an easy and useful noninvasive test for predicting liver fibrosis in patients with chronic viral hepatitis.

BACKGROUND: Liver biopsy-the gold standard in assessing liver histology-is recommended before all antiviral treatment. However, this procedure may cause complications, is costly, and is limited by sampling errors. Hence, noninvasive tests have been proposed to assess the severity of hepatic fibrosis. We propose a novel noninvasive index for predicting liver fibrosis, named fibro-quotient (FibroQ), and compared the diagnostic accuracies of FibroQ, aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and AST/alanine aminotransferase (ALT) ratio (AAR). METHODS: This retrospective cohort study included 140 consecutive patients with chronic viral hepatitis who had undergone percutaneous liver biopsy before treatment at the Chang Gung Memorial Hospital, Chiayi from May 2005 through December 2007. The clinical data including sex, age, AST, ALT, platelet count, prothrombin time (PT) international normalized ratio (INR), and the Metavir fibrosis score (F0 to F4) of liver histology were recorded. APRI, AAR, and FibroQ were calculated. Receiver operating characteristic (ROC) curves were constructed to compare the accuracies of these three noninvasive tests in predicting significant fibrosis in patients with chronic viral hepatitis. RESULTS: FibroQ performed better than APRI, but was equal to AAR, in the prediction of significant fibrosis [area under the receiver operating characteristic curve (AUC): 0.783 vs 0.631 (p = 0.02) and 0.783 vs 0.733 (p = 0.26), respectively] and cirrhosis (AUC: 0.791 vs 0.634 (p = 0.03), and 0.791 vs 0.782 (p= 0.47), respectively). Using FibroQ below the lower cutoff value (0.6) and above the higher cutoff value (1.6), 108 of 140 (77.1%) patients could be identified correctly to have or not have significant fibrosis. CONCLUSION: FibroQ, a novel noninvasive test, is an useful and easy tool to evaluate liver fibrosis in patients with chronic viral hepatitis and has better accuracy than APRI and is equal to AAR. Further prospective studies are warranted to validate its efficacy.

Endoscopic submucosal dissection for gastric epithelial tumors: a multicenter study in Taiwan.

BACKGROUND/PURPOSE: Endoscopic submucosal dissection (ESD) is an advanced endoscopic procedure to resect early gastric cancer (EGC). The purpose of this study was to determine the effectiveness and complications of ESD for gastric epithelial tumors in Taiwan. METHODS: We retrospectively analyzed the efficacy and outcome of ESD in patients who received ESD for gastric epithelial tumors between June 2004 and August 2007. RESULTS: A total of 70 patients with gastric epithelial tumors were treated by ESD. The mean age was 66.5 +/- 12.9 years (range, 35-84 years). The mean size of the gastric epithelial tumors was 1.85 +/- 0.81 cm. The mean size of resected specimens was 3.26 +/- 1.39 cm. The one-piece resection rate was 91.4% (64/70). The median operation time was 92.4 minutes. The complicating bleeding and perforation rates were 5.7% (4/70) and 4.3% (3/70), respectively. Emergency surgery was performed for three patients with perforations. The local recurrence rate of gastric cancer was 2.8%. Except for one patient who died of congestive heart failure and another who died of stroke, the remaining 68 patients (97.1%) survived. CONCLUSION: ESD is a promising local curative treatment option for EGC in Taiwan but it still carries risks of perforation and bleeding. The education and learning curve of endoscopists will improve the outcome of this procedure.

Endoscopic submucosal dissection for early gastric cancers: experience from a new endoscopic center in Taiwan.

GOAL: To evaluate the efficacy of endoscopic submucosal dissection (ESD) for early gastric cancers (EGCs) at a new endoscopic center. BACKGROUND: ESD is a novel technique that can facilitate en-bloc resection of EGCs, but seldom reported outside Japan. STUDY: A total of 25 consecutive patients (25 lesions) underwent ESD from June 2004 to March 2006. Patients were divided into 2 groups: group A underwent ESD from June 2004 to May 2005 (introduction stage) and group B from June 2005 to March 2006. The following data were obtained: tumor size, tumor location, operative time, and major complication. RESULTS: The complete resection was achieved in 20 lesions (success rate 80%). Four out of 10 lesions from group A were removed by conventional endoscopic mucosal resection (EMR) piecemeally after ESD failure. Conversely, 14 patients from group B (n=15) were resected by ESD en-bloc (success rate 93.3%). One patient with microscopic residual tumor after ESD was further treated by surgical resection. The time required for resection was significantly longer in group A when compared with group B (130.5 min vs. 81.5 min, P<0.05). Postoperative complication rate between the 2 groups were similar. One patient with piecemeal EMR recurred in follow-up, and was further treated successfully by EMR. CONCLUSIONS: ESD is an ideal method for EGC treatment, but it may result in a risk of complication. The complete resection rate can be improved by endoscopist's experience. Sophisticated endoscopic hemostasis and clipping skills are essential prior ESD procedures. Conventional EMR techniques are also obligatory during the beginning period.

Clinical features and outcome of chronic viral hepatitis with acute exacerbation in patients with concurrent infections of hepatitis B and C virus.

BACKGROUND/AIMS: Studies have shown that concurrent infection of hepatitis B virus and hepatitis C virus may be associated with severe forms of chronic liver disease or with rapid progression. However, very little is known about the role and course of concurrent HBV and HCV infection in patients with acute viral hepatitis. METHODS: This study retrospectively compared the clinical features of 83 patients diagnosed with HBV- or HCV-related chronic hepatitis with acute exacerbation (12 with concurrent HBV and HCV infection, 46 with HBV infection alone, and 25 with HCV infection alone) encountered at Chia-Yi Chang Gung Memorial Hospital, Taiwan, between January 2003 and December 2005. RESULTS: The clinical course of chronic hepatitis with acute exacerbation in patients with concurrent HBV and HCV infection is similar to patients with single HBV infection, and more severe than patients with single HCV infection, evidenced by increased hepatic decompensation (P = 0.05), failure (P = 0.036), and mortality (P = 0.036). Elevated serum HCVRNA-negative percentage in HBVDNA-positive patients and low serum HBVDNA concentrations in HCVRNA-positive patients imply reciprocal interference of HBV and HCV in patients with concurrent HBV and HCV infections during acute-phase hepatitis. In patients with concurrent HBV and HCV infection, the mortality rate for detectable HBVDNA patients seemed higher than that for undetectable HBVDNA patients, although it did not reach statistical significance (P = 0.066). CONCLUSIONS: Virus interference existed in chronic hepatitis with acute exacerbation patients with concurrent HBV and HCV infections. Clinical outcome for patients positive for serum HBVDNA was much worse than those negative for serum HBVDNA. When chronic hepatitis with acute exacerbation occurs in patients with concurrent HBV and HCV infection, aggressive management should be investigated and antiviral therapy targeting of HBV infection should be administered early.

Predictive role of nuclear factor-kappaB activity in gastric cancer: a promising adjuvant approach with caffeic acid phenethyl ester.

BACKGROUND: The biologic significance of nuclear factor-kappaB (NF-kappaB) activation in human gastric cancer is unclear. We clarify the clinical significance of NF-kappaB activation and its relationship to Helicobacter pylori infection, a well-known pathogenesis of gastric cancer. Moreover, we examine the effects and underlying mechanisms induced by caffeic acid phenethyl ester (CAPE), an inhibitor of NF-kappaB, for gastric carcinoma. METHODS: NF-kappaB was located immunohistochemically in 90 human gastric cancer specimens and 50 nonmalignant gastric specimens. The correlations between NF-kappaB activation, pathologic staging, and H. pylori infection were analyzed. We also performed electrophoretic mobility gel shift assay, real-time reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay to evaluate the responses of AGS (a gastric adenocarcinoma epithelial cell line) human gastric cancer cells subsequent to H. pylori infection or CAPE treatment. RESULTS: Nuclear expression of NF-kappaB was significantly more frequently observed in gastric cancer tissues than in nonmalignant gastric tissues (31% vs. 4%, P=0.0001). The activity of NF-kappaB and the expressions of MMP-9, IL-1beta, and IL-8 in AGS cells were activated by H. pylori infection. However, the augmented responses could be significantly reversed by CAPE treatment. Moreover, in vitro studies showed that CAPE inhibits tumor growth and capacity for invasion. CONCLUSIONS: NF-kappaB activation is related to carcinogenesis, tumor aggression, and H. pylori infection with the increased expression of MMP-9, IL-1beta, and IL-8. Moreover, NF-kappaB inhibitors or anti-inflammatory agents such as CAPE might be new adjuvant agent against invasive gastric carcinoma.

Metastatic Merkel cell carcinoma in the rectum: report of a case.

Merkel cell carcinoma is a rare, aggressive skin malignancy of neuroendocrine origin with predominant occurrence in the elderly males. Approximately 50 percent of patients with Merkel cell carcinoma develop distant metastasis at some point during the disease course; hence, Merkel cell carcinoma always has a poor prognosis. Distant metastasis has never been disclosed in the rectum to the best of our knowledge. We present a 76-year-old male with clinical manifestation of massive hematochezia and final diagnosis of metastatic Merkel cell carcinoma in the rectum. We conclude that radical resection of rectal metastatic Merkel cell carcinoma is important in the management strategy of a patient with recurrence and lymph node metastases.

Effect of oral esomeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers.

BACKGROUND: After endoscopic treatment of bleeding peptic ulcer, a high-dose infusion of omeprazole substantially reduces the risk of recurrent bleeding. The role of oral proton pump inhibitors for these patients is uncertain. The purpose of the present study was to assess whether the use of oral esomeprazole would reduce the frequency of recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. METHODS: Patients with actively bleeding ulcers or ulcers with non-bleeding visible vessels were treated with an epinephrine injection followed by thermocoagulation. After hemostasis had been achieved, they were randomly assigned in a double-blind fashion to receive esomeprazole (40 mg p.o. twice daily for 3 days) or placebo. The outcome measures studied were recurrent bleeding, blood transfusion requirement, surgery and death. RESULTS: A total of 70 patients were enrolled, 35 in each group. Bleeding recurred within 30 days in two patients (5.7%) in the esomeprazole group, as compared with three (8.6%) in the placebo group (P = 0.999). Blood transfusion requirement was 2.8 +/- 1.4 units in the esomeprazole group and 2.7 +/- 1.3 units in the placebo group (P = 0.761). Duration of hospitalization was 4.82 +/- 1.8 days in the esomeprazole group and 4.58 +/- 2.7 days in the placebo group (P = 0.792). No patients needed surgery for control of bleeding and no patients died in both groups. CONCLUSIONS: After successful endoscopic treatment of bleeding peptic ulcer, oral use of esomeprazole might offer no additional benefit on the risk of recurrent bleeding.

Endoscopic resection of a large colonic leiomyoma.

A 48-year old man suffered from intermittent hematochezia and abdominal cramping over a period of four weeks. A colonoscopy revealed a 4.5 cm semi-pedunculated tumor in the transverse colon. Using a 2-channel colonoscope, the tumor was successfully removed with an electro-surgical snare after normal saline submucosal injection. Microscopic examination revealed it to be a smooth muscle tumor without mitosis. The patient recovered well, and did not have a residual tumor in a follow-up colonoscopy. We found no reports of a colonic leiomyoma larger than 3 cm which was completely removed by a colonoscope. According to the case presented here, intraluminal colonic leiomyoma can be completely resected with skillful manipulation of a colonoscope, even if the tumor is as large as 4.5 cm. Successful endoscopic polypectomy of colonic leiomyoma reduces the cost of treatment and eliminates unnecessary surgery.