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Herpes simplex virus (HSV) infection is quite common in adults and neonates and is associated with oral mucocutaneous lesions and/or genital infections. Therefore, the aim of this present study was to determine the in-vitro cytotoxicity and anti-herpes simplex virus (1 and 2) activity of methanol extract of Strophanthus hispidus (S. hispidus ) DC (Stem bark) and his HPLC fingerprint profile. The cytotoxicity test on Vero cells was performed by MTT assay and various concentrations of extract less than the maximum nontoxic concentration were used against Vero cells for anti-HSV-1 and ant-HSV-2 effects by plaque assay. The CC50 values of methanolic extracts of S. hispidus (stem bark) and acyclovir against Vero cells were 94.46 µg/mL and 118.78 µg/mL, respectively. Whereas the EC50 and selectivity index values of this extract against herpes simplex virus 1 and herpes simplex virus 2 strains were 36.60 µg/mL (SI=2.58) and 39.47 µg/mL (SI=2.39), respectively. HPLC finger-printing of this extract was developed and showed seven major compounds including ascorbic acid, quercetin, resorcinol and gallic acid represented in large amount. In conclusion, the methanolic extract of Strophanthus hispidus DC(stem bark) has good antiherpetic activity against HSV- 1 and HSV-2 but it is also highly toxic. Therefore, it will be important to separate toxic molecules from those responsible of the antiherpetic activity by bio guided fractionation procedures.

We have previously developed a robust regimen for tolerance induction in murine models of islet cell transplantation using pre- and posttransplant infusions of donor splenocytes (SPs) treated with a chemical cross-linker ethylcarbodiimide (ECDI). However, the requirement for large numbers of fresh donor SPs for ECDI coupling impairs its clinical feasibility, and additionally, the compatibility of this tolerance regimen with commonly used immunosuppressive drugs is largely unknown. In the current study, we demonstrate that equivalent tolerance efficacy for islet cell transplantation can be successfully achieved not only with a significantly lower dose of ECDI-SPs than originally established but also with culture-expanded donor B-cells or with soluble donor antigens in the form of donor cell lysate, which is ECDI coupled to recipient SPs. We further demonstrate that tolerance induced by donor ECDI-SPs is dependent on a favorable apoptotic-to-necrotic cell ratio post-ECDI coupling and is not affected by a transient course of conventional immunosuppressive drugs including tacrolimus and mycophenolate mofetil. While splenic antigen-presenting cells of the recipient play an important role in mediating the tolerogenic effects of donor ECDI-SPs, splenectomized recipients can be readily tolerized and appear to employ liver Kupffer cells for uptaking and processing of the ECDI-SPs. We conclude that infusion of donor ECDI-SPs is a versatile tolerance strategy that has a high potential for adaptation to clinically feasible regimens for tolerance trials for human islet cell transplantation.

Six aromatic secondary metabolites, pestalone (1), emodin (2), phomopsilactone (3), pestalachlorides B (4), C (5), and D (6), were isolated from Pestalotiopsis sp. FKR-0115, a filamentous fungus collected from white moulds growing on dead branches in Minami Daito Island. The efficacy of these secondary metabolites against methicillin-resistant Staphylococcus aureus (MRSA) with and without meropenem (β-lactam antibiotic) was evaluated using the paper disc method and broth microdilution method. The chemical structures of the isolated compounds (1-6) were characterised using spectroscopic methods, including nuclear magnetic resonance and mass spectrometry. All six isolated compounds exhibited synergistic activity with meropenem against MRSA. Among the six secondary metabolites, pestalone (1) overcame bacterial resistance in MRSA to the greatest extent.

Determining the structures of new natural products from marine species not only enriches our understanding of the diverse chemistry of these species, but can also lead to the discovery of compounds with novel and/or important biological activities. Herein, we describe the isolation of isomaneonene C ( 1 ), a new halogenated C 15 acetogenin, and three known compounds, α -snyderol ( 2 ), cis -maneonene D ( 3 ), and isomaneonene B ( 4 ), from the organic extract obtained from the red alga Laurencia cf. mariannensis collected from Iheya Island, Okinawa, Japan. The structures of these secondary metabolites were elucidated spectroscopically. All compounds were inactive at 30 μg/disc against methicillin-resistant Staphylococcus aureus (MRSA) in combination treatment with a β - lactam drug, meropenem.

Although medicinal plants are beneficial, they also can be important risk factors for the development of acute and chronic kidney injury, as well toxicity of other solid organs. There are a lack of reports of adverse kidney events and drug interactions resulting from medicinal plants owing to a lack of professional surveillance and specific data on kidney toxicity, especially in low-resource settings. Within the context of increased medicinal plant use and lack of effective regulatory control, safety is a key priority issue. We review the benefits and adverse effects of medicinal plants with particular reference to nephrotoxicity encountered in the Democratic Republic of Congo in sub-Saharan Africa., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The red alga Laurencia nipponica comprises various chemical races distributed relative to the ocean current in Japanese coastal areas. We investigated the chemical compositions and chemical races of L. nipponica distributed from the Kunashiri and Etorofu Islands, the confluence of the Soya warm current and Oya-shio cold current. Two new halogenated secondary metabolites, deacetylneonipponallene (1) and neopacifenol (2), along with four known compounds, deoxyprepacifenol (3), pacifenol (4), halo-chamigrene diether (5), and isolaurallene (6) were isolated from L. nipponica collected at Chikappunai, Kunashiri Island, while Zaimokuiwa (Kunashiri Island) and Sana (Etorofu Island) populations contained 3, 7-hydroxylaurene (7), 2,10-dibromo-3-chloro-9-hydroxy-α-chamigrene (8), and (3Z)-laurefucin (9). The structures of 1 and 2 were established using spectroscopic methods. The chemical races of L. nipponica distributed in this area were divided into 6- and 9-producing races. Interestingly, both races contained 4 as an additional race-index, as well as its derivatives, 2 and 5. To the best of our knowledge, this is the first example of a race comprising a mixture of two race-index compounds, suggesting that the convergence of two currents causes the production of new and diverse chemical races in this species., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

A 71-year-old man was referred to our hospital and was diagnosed with jaundice and a liver function disorder. Although we suspected an intraductal papillary neoplasm of the bile duct (IPNB)-derived caudate branches on the basis of contrast-enhanced CT, MRI, and endoscopic retrograde cholangiopancreatography, we could not clearly identify the tumor. Therefore, we examined the lesion using endoscopic ultrasonography (EUS). We could visualize an iso-hyperechoic elevated tumor in the caudate branches. The tumor was observed as a hypervascular lesion using contrast-enhanced EUS, which is useful in preoperatively diagnosing IPNB and detecting the presence of lesions.

Pancreatic cancer is one of the most fatal types of cancer in developed countries. Most patients have locally advanced or metastatic cancerous lesions when they are diagnosed, due to the progressive, invasive and metastatic capacity of this disease to liver, lymph nodes and distant organs during early stages. Although the only curative therapy is complete surgical resection, the disease has usually already progressed by the time of diagnosis, and the majority of patients have metastatic disease. Therefore, palliative chemotherapy remains the only therapy for patients with progressive disease. Gemcitabine has been used for pancreatic cancer as the most effective anticancer drug. However, there are many cases resistant to gemcitabine. Thus, a better understanding of the molecular mechanisms of resistance to gemcitabine is essential to allow it to be used more effectively. Our previous proteomic studies demonstrated that the expression of heat-shock protein 27 (HSP27) was increased in gemcitabine-resistant pancreatic cancer cells and this might play a role in determining the sensitivity of pancreatic cancer to gemcitabine. Increased HSP27 expression in tumor specimens was related to resistance to gemcitabine and a shorter survival period in patients with pancreatic cancer. Furthermore, it has been shown that treatment strategies combining the HSP inhibitor KNK437 or interferon-γ (IFN-γ) with gemcitabine, were effective in gemcitabine-resistant pancreatic cancer cells in vitro. Furthermore, combined therapy of gemcitabine with IFN-γ of gemcitabine-resistant pancreatic cancer-bearing nude mice showed synergistic therapeutic effects on gemcitabine-resistant pancreatic cancer bearers. In this review, we summarize the current understanding of HSP27 and its role in gemcitabine resistance.

TS-1 is an oral anticancer agent containing two biochemical modulators for 5-fluorouracil (5-FU) and tegafur (FT), a metabolically activated prodrug of 5-FU. TS-1 has been recognized as an effective anticancer drug using standard therapies for patients with advanced pancreatic cancer along with gemcitabine. However, a high level of inherent and acquired tumor resistance to TS-1 induces difficulty in the treatment. To identify proteins linked to the TS-1-resistance of pancreatic cancer, we profiled protein expression levels in samples of TS-1-resistant and -sensitive pancreatic cancer cell lines by using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The cytotoxicity of a 5-FU/5-chloro-2,4-dihydroxypyridine (CDHP) combination towards pancreatic cancer cell lines was evaluated by MTS assay. Panc-1, BxPC-3, MiaPaCa-2 and PK59 showed high sensitivity to the 5-FU/CDHP combination (TS-1-sensitive), whereas PK45p and KLM-1 were much less sensitive (TS-1-resistant). Proteomic analysis showed that eleven spots, including T-complex protein 1 subunit beta, ribonuclease inhibitor, elongation factor 1-delta, peroxiredoxin-2 and superoxide dismutase (Cu-Zn), appeared to be down-regulated, and 29 spots, including hypoxia up-regulated protein 1, lamin-A/C, endoplasmin, fascin and annexin A1, appeared to be up-regulated in TS-1-resistant cells compared with -sensitive cells. These results suggest that the identified proteins showing different expression between TS-1-sensitive and -resistant pancreatic cancer cells possibly relate to TS-1-sensitivity. These findings could be useful to overcome the TS-1-resistance of pancreatic cancer cells.

We review the current situation concerning molecular biological analysis in respect of pancreatic cancer, using specimens obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). K-ras, p53, p16, DPC4/SMAD4, telomerase activity are used for discrimination between tumor-forming pancreatitis and pancreatic cancer. Examination of heat shock protein (HSP) 27, ribonucleotide reductase, and other factors are examined in order to test the sensitivity to Gemcitabin. Comparative genomic hybridization analysis for pancreatic cancer specimens obtained by EUS-FNA was reported to be useful for evaluate the biological characteristics of pancreatic cancer before treatment. It is expected that the genetic diagnosis using EUS-FNA specimens will not only positively contribute to improving the diagnostic performance, but it will also provide valuable information for carrying out tailor-made treatment., (© 2011 The Authors. Digestive Endoscopy © 2011 Japan Gastroenterological Endoscopy Society.)

Background and Purpose: The present study retrospectively analyzed the clinical impact of endoscopic papillectomy on the selection of a treatment strategy for patients with benign-malignant borderline lesions of the major duodenal papilla., Patients and Methods: Between November 1995 and July 2009, 28 patients were selected for endoscopic papillectomy. The clinical impact of endoscopic papillectomy was assessed. Snare resection was performed in a radical fashion., Results: An endoscopic papillectomy was technically feasible in all patients. En bloc excision was achieved in 22 cases (79%). The final histopathological diagnoses of the endoscopic specimen were 17 adenoma (61%), 7 carcinoma in adenoma (25%), and 4 adenocarcinoma (14%). Two out of the four adenocarcinoma cases were referred for surgery. The other two patients with negative margins have not experienced recurrences during the follow-up period. A residual tumor was detected in 1 out of 17 cases (6%) of adenoma and 2 out of 7 cases (29%) of carcinoma in adenoma., Conclusions: Endoscopic papillectomy is therefore considered to be an effective treatment for patients with a benign-malignant borderline lesion of the major duodenal papilla. This method also has an important clinical impact because it provides an accurate diagnosis, aids in the selection of an appropriate treatment strategy, and reduces unnecessary surgery.

Background: There is no consensus on the choice of either unilateral or bilateral drainage in stent placement for patients with unresectable hilar biliary obstruction. The aim of the present study was to clarify which drainage method is superior., Methods: We retrospectively reviewed 82 patients with hilar biliary obstruction who underwent metallic stenting. These patients were divided into a unilateral drainage group (Uni group) and a bilateral drainage group (Bi group)., Results: There was no significant difference between the groups in median survival time, median stent patency period, and median complication-free survival time. The most frequent complication was stent obstruction, followed by cholangitis. Liver abscess was found at a higher frequency in the Bi group (17.6%) than in the Uni group (1.5%) (P=0.0266). There was no significant difference between the groups in the occurrence of two or more complications (P=0.247), life-threatening severe complications (P=0.0577), and stent obstruction by sludge (P=0.0912)., Conclusion: When compared with bilateral biliary drainage, unilateral biliary drainage is associated with a lower incidence of liver abscess as well as a comparable outcome of stent patency time and complication-free survival. We therefore propose that hilar biliary obstruction can be treated first by unilateral drainage with a metallic stent and by bilateral drainage only in patients who develop cholangitis in the contralateral biliary tree., (© 2010 The Authors. Digestive Endoscopy © 2010 Japan Gastroenterological Endoscopy Society.)

Background: Our previous proteomic study demonstrated that expression of heat shock protein 27 (HSP27) is upregulated in gemcitabine (GEM)-resistant pancreatic cancer cells and that it suppressed the cytotoxic effect of GEM on the cells. This report describes the benefits of a treatment strategy combining the HSP inhibitor KNK437 with GEM for GEM-resistant pancreatic cancer cells., Methods: We used 2 human pancreatic cancer cell lines, GEM-sensitive KLM1 and GEM-resistant KLM1-R. KLM1-R was treated with KNK437, and we examined the expression of HSP27 by Western blotting. The cytotoxicity of GEM and KNK437 for KLM1-R was investigated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay., Results: The expression of HSP27 in KLM1-R was dramatically reduced by KNK437. In addition, the in vitro antitumor cytotoxic effect of GEM on KLM1-R was enhanced by combination treatment with KNK437 compared to GEM alone., Conclusion: This study supports the potential therapeutic benefits of a treatment strategy combining KNK437 with GEM., (Copyright © 2010 S. Karger AG, Basel.)

The prognosis of patients with pancreatic cancer is very poor because of late diagnosis and the lack of response to various therapies. Pancreatic cancer is generally resistant to chemotherapy and is highly fatal. Gemcitabine (GEM) appears to be the only effective agent for treatment of pancreatic cancer. However, a high level of inherent and acquired tumor resistance makes the clinical impact of GEM modest. Proteomic differential display analysis for GEM-sensitive human pancreatic adenocarcinoma cell line KLM1 and GEM-resistant KLM1-R cells by using two-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry produced 33 protein spots. Of these, 23 were up-regulated and 10 were down-regulated in KLM1-R compared to KLM1 cells. The up-regulated proteins include acidic leucine-rich nuclear phosphoprotein 32 family member A, reticulocalbin-1, gamma-synuclein, microtubule-associated protein RP/EB family, sialic acid synthase, peptidyl-prolyl cis-trans isomerase A, far upstream element-binding protein 2 and catalase. The down-regulated proteins include far upstream element-binding protein 1, gamma-synuclein, galectin-1 and stathmin. Two spots of heat-shock protein 27 were up-regulated in KLM1-R cells. These results suggest an important complementary role for proteomics in the identification of proteins which may play a role in the poor response of pancreatic cancer to GEM.

Background: Gemcitabine (2'-deoxy-2'-difluorodeoxycytidine: Gemzar) (GEM) appears to be the only effective anticancer drug for pancreatic cancer, but it has little impact on outcome due to a high level of inherent and acquired tumor resistance. Our previous proteomic study demonstrated that the expression of three spots of heat-shock protein 27 (HSP27) was increased in GEM-resistant pancreatic cancer cells and could play a role in determining the sensitivity of pancreatic cancer to GEM., Materials and Methods and Results: In the present study, using one-dimensional and two-dimensional Western blotting, we elucidated that these three spots of HSP27 were phosphorylated in GEM-resistant pancreatic cancer cell line, KLM1-R., Conclusion: Phosphorylated HSP27 may play an important role in the resistance to GEM, and it could also be a possible biomarker for predicting the response of pancreatic cancer patients to treatment with GEM.

We report the successful retrieval of an impacted mechanical lithotripsy basket. In a patient with two large common bile duct stones, the basket with the entrapped stone was impacted within the mid-common bile duct. We then attempted to use another mechanical lithotripter; however the central wire of the basket fractured at the handle portion. Grasping a few wires of the impacted basket with rat-tooth forceps allowed the wires of the basket to slip away from the stone. The present report describes the safe and effective use of rat-tooth forceps in the management of an impacted lithotripter basket.

Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for the treatment of patients with pancreaticobiliary disorders, but endoscopic therapy is very difficult to carry out in patients with a Roux-en-Y anastomosis. We herein present the results of ERCP for patients with a Roux-en-Y anastomosis using a double-balloon endoscope. Six patients (six men with a mean age of 69 years) who had undergone prior gastric resection with Roux-en-Y reconstruction were enrolled in the present study and underwent ERCP and associated procedures. ERCP was carried out with a double balloon endoscope, which has one balloon attached to the tip of the endoscope and another attached to the distal end of the soft overtube. In all patients, entering the Y loop was successfully accomplished, and the papilla of Vater was also reached in all cases (100%). Cannulation was successful in four patients (66.7%). The final diagnosis was choledocholithiasis in two patients, biliary fistula in one patient and pancreatic cancer in one patient. A needle-knife precut papillotomy was carried out after placement of a bile duct stent in two patients, and injection of N-butyl-2-cyanoacrylate into a biliary fistula was carried out in one patient. None of the patients suffered from any complications. A double balloon endoscope is therefore considered to be useful for carrying out ERCP and associated procedures in patients with a Roux-en-Y anastomosis.