Assessing the Potential Apoptotic Effects of Different Hydatid Cyst Fluids on Human Healthy Hepatocytes and Hepatocellular Carcinoma Cells.

Cystic Echinococcosis (CE) is a zoonotic infection caused by the larval form of Echinococcus granulosus in humans. Emerging evidence suggests an intriguing inverse association between E. granulosus infection and the occurrence of cancer. This study aimed to investigate the influence of diverse host-derived hydatid cyst fluids (HCF) with distinct genotypes on human liver hepatocytes (HC) and hepatocellular carcinoma cells (HepG2). Specifically, we examined their effects on cell proliferation, apoptosis sensitivity (BAX/BCL-2), apoptosis-related p53 expression, and the expression of cancer-related microRNA (hsa-miR-181b-3p). Cell proliferation assays, real-time PCR, and ELISA studies were conducted to evaluate potential anti-cancer properties. The findings revealed that animal-origin HCF (G1(A)) induced direct cell death by augmenting the susceptibility of HepG2 cells to apoptosis. Treatment with both G1(A) and G1(H) HCF sensitized HepG2 and HC cell lines to apoptosis by modulating the BAX/BCL-2 ratio, accompanied by upregulation of the p53 gene. Additionally, G1(A) HCF and human-derived HCFs (G1(H), G7(H)) reduced the expression of miR-181b-3p in HepG2 cells. Consequently, this study demonstrates the potential anti-cancer effect of HCF in HepG2 cells and provides the first comparative assessment of HCFs from human and animal sources with diverse genotypes, offering novel insights into this field.

Plasmodium infection inhibits tumor angiogenesis through effects on tumor-associated macrophages in a murine implanted hepatoma model.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death in China. The lack of an effective treatment for this disease results in a high recurrence rate in patients who undergo radical tumor resection, and the 5-year survival rate of these patients remains low. Our previous studies demonstrated that Plasmodium infection provides a potent antitumor effect by inducing innate and adaptive immunity in a murine Lewis lung carcinoma (LLC) model. METHODS: This study aimed to investigate the inhibitory effect of Plasmodium infection on hepatocellular carcinoma in mice, and various techniques for gene expression analysis were used to identify possible signal regulation mechanisms. RESULTS: We found that Plasmodium infection efficiently inhibited tumor progression and prolonged survival in tumor-bearing mice, which served as a murine implanted hepatoma model. The inhibition of tumor progression by Plasmodium infection was related to suppression of tumor angiogenesis within the tumor tissue and decreased infiltration of tumor-associated macrophages (TAMs). Further study demonstrated that matrix metalloprotease 9 (MMP-9) produced by TAMs contributed to tumor angiogenesis in the tumor tissue and that the parasite-induced reduction in MMP-9 expression in TAMs resulted in the suppression of tumor angiogenesis. A mechanistic study revealed that the Plasmodium-derived hemozoin (HZ) that accumulated in TAMs inhibited IGF-1 signaling through the PI3-K and MAPK signaling pathways and thereby decreased the expression of MMP-9 in TAMs. CONCLUSIONS: Our study suggests that this novel approach of inhibiting tumor angiogenesis by Plasmodium infection is of high importance for the development of new therapies for cancer patients. Video abstract.

Discovery of Carcinogenic Liver Fluke Metacercariae in Second Intermediate Hosts and Surveillance on Fish-Borne Trematode Metacercariae Infections in Mekong Region of Myanmar.

Countries of lower Mekong regions are highly alarmed by the spread of fish-borne trematode infections, i.e., small liver flukes and minute intestinal flukes especially in Thailand, Lao People's Democratic Republic (Lao PDR), Vietnam, Cambodia and Myanmar. Moreover; the incidence of cholangiocarcinoma has also been increasing in the endemic area of liver fluke infections. Only a few reports have been published concerning the fish-borne trematodes infections in the central region of Myanmar. However; there is still a lack of information regarding the status of trematodes infections in second intermediate hosts in the Mekong region of Myanmar. Therefore, we conducted surveillance on the distribution of trematode metacercariae in small cyprinoid fishes collected from the Mekong region of Myanmar. A total of 689 fishes (12 different species of cyprinoid fishes) have been collected and examined by pepsin digestion methods. We discovered four species of fish-borne trematode metacercariae infections, i.e., carcinogenic liver fluke, Opisthorchis viverrini; minute intestinal flukes, Haplorchis taichui; Haplorchis pumilio and Haplorchoides sp. in Tachileik, the Mekong Region of Myanmar. The outcome of this study could be a useful index for the fish-borne zoonotic trematode epidemiology in the Mekong area. Besides, the results of our study contribute to filling the gap of information necessary for the control and prevention of fish-borne trematode zoonotic infections in the Mekong region.

Animation as Supplementary Learning Material About Carcinogenic Liver Fluke in Classes for Primary Schoolchildren.

Carcinogenic liver fluke is still an issue of great concern in some countries of Southeast Asia, particularly in Thailand, Cambodia, the Lao People's Democratic Republic, and Vietnam. The infection, caused by Opisthorchis viverrini, is associated to cholangiocarcinoma and is endemic among human populations for whom raw fish is frequently consumed. Prevention and health education are required. Therefore, this study aimed to evaluate the effectiveness of educational intervention to improve knowledge among primary schoolchildren based on animation-assisted education. In this study, 80 participants (40 participants in the experimental group and 40 participants in the comparison group) were selected in 2018. The effectiveness of an interactive animation program in improving the knowledge of students studying liver fluke was determined based on scores on tests given before and immediately after completion of a 4.29-min animated program on the liver fluke life cycle, risk factors, disease, diagnosis, treatment, prevention, and control. Data were analyzed using SPSS-22 via paired t tests and independent samples t tests at a significance level of 0.05. A marked and significant improvement was observed in the immediate posttest compared with the pretest scores. More importantly, the students who had used the animated program achieved a significantly higher score on the final test than the comparison group. The results offered in the first report show that the use of the animated program facilitated education about liver fluke. It is strongly believed that animations are good supplementary learning materials for students, particularly for learning about serious concepts.

Hepatocellular carcinoma-associated antigen 59 of Haemonchus contortus modulates the functions of PBMCs and the differentiation and maturation of monocyte-derived dendritic cells of goats in vitro.

BACKGROUND: Hepatocellular carcinoma-associated antigen 59 (HCA59), which is one of the most important excretory/secretory products of Haemonchus contortus (HcESPs), is known to have antigenic functions. However, its immunomodulatory effects on host cells are poorly understood. METHODS: Here, we cloned the HCA59 gene and expressed the recombinant protein of HCA59 (rHCA59). Binding activities of rHCA59 to goat peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs) were checked by immunofluorescence assay (IFA) and the immunoregulatory effects of rHCA59 on cytokine secretions, cell migration, cell proliferation, nitric oxide production, and changes in expression of genes in related pathways were observed by co-incubation of rHCA59 with goat PBMCs and DCs. Monocyte phagocytosis and characterization of goat blood DC subsets were detected by flow cytometry. RESULTS: The IFA results revealed that rHCA59 could bind to PBMCs and DCs. Treatment of PBMCs with rHCA59 significantly increased cellular proliferation and NO production in a dose-dependent manner, while cell migration was vigorously blocked. Treatment with rHCA59 significantly suppressed monocytes phagocytosis. The quantity of surface marker CD80 on DCs increased significantly after rHCA59 treatment. In addition, the expression of genes included in the WNT pathway was related to the differentiation and maturation of DCs, and the production of IL-10 and IL-17 produced by PBMCs was altered. CONCLUSIONS: Our findings illustrated that rHCA59 could enhance host immune responses by regulating the functions of goat PBMCs and DCs, which would benefit our understanding of HCA59 from parasitic nematodes contributing to the mechanism of parasitic immune evasion.

Virologic control and severity of liver disease determine survival after radiofrequency ablation of hepatocellular carcinoma on cirrhosis.

BACKGROUND: We aimed to identify the main determinants of long-term overall survival (OS), including virologic control, and recurrence after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) on cirrhosis. METHODS: Cirrhotic patients treated by RFA for HCC within Milan criteria were included. Associations between patient features and events were estimated by the Kaplan-Meier method with the log rank test and using uni/multivariate Cox models. RESULTS: 389 cirrhotic patients (Child-Pugh A 86.6%, 473 tumors) were included. OS was 79.8%, 42.4% and 16%, and overall tumor recurrence 45%, 78% and 88% at 2, 5 and 10 years, respectively. In multivariate analysis, age, Child-Pugh, GGT, HCC near major vessels, esophageal varices, alkaline phosphatase and HBV predicted OS. Gender, ALT, AFP and alcohol intake were associated with tumor recurrence. Multinodular HCC (19.5%) was associated with risk of tumor recurrence outside Milan criteria. HBV patients had longer OS than other patients (P = 0.0059); negative HBV PCR at RFA was associated with decreased tumor recurrence (P = 0.0157). Using time-dependent analysis in HCV patients, a sustained virologic response was associated with increased OS (124.5 months) compared to other patients (49.2 months, P < 0.001). CONCLUSION: Virologic response and severity of underlying liver disease were the main determinants of long-term OS after RFA for HCC developing on cirrhosis.

[Hepatic Parasitosis: Atypical presentation] / Parasitosis Hepática: Presentación atípica.

Benign solid liver tumors are composed by a heterogeneous group of lesions. Hepatic parasitosis is an infrequent etiological cause of benign solid liver tumors. Objective. To present the case of a patient with benign solid liver tumors treated with right portal vein embolization and, later, with hepatectomy. Clinical case. 60-year-old, male patient diagnosed with multiple solid liver tumors, due to a generalized case of jaundice. The decision to perform surgery was made on the basis of the clinical symptoms and the impossibility of discarding malignancy through complementary tests. Before surgery, hepatic volumetry and right portal vein embolization were done to increase future hepatic remnant. Right hepatectomy and hepatic resection of segment IVa were performed. The patient evolved positively from jaundice and the anatomopathological results showed a lesion related to hepatic parasitosis. Conclusion. In the presence of a solid liver tumor, it is necessary to rule out the malignant etiology of the lesion. If this is not possible, or if the patient continues with the symptomatology, surgical resection is prescribed, taking into account the volume of the hepatic gland and future hepatic remnant.

Los tumores hepáticos sólidos benignos están formados por un grupo heterogéneo de lesiones. Las parasitosis hepáticas conforman una causa etiológica poco frecuente de tumores hepáticos sólidos benignos. Objetivo. Reportar el caso de un paciente con tumores hepáticos solidos benignos tratado con embolización portal derecha y posteriormente hepatectomía. Caso clínico. Paciente de 60 años, sexo masculino, al cual se le diagnostican múltiples tumores hepáticos sólidos, debido a cuadro de ictericia generalizada. Debido al cuadro sintomático, y al no poder descartar malignidad con las pruebas complementarias, se decide realizar cirugía. Previamente se realiza volumetría de la glándula hepática y embolización portal derecha para aumentar el remanente hepático futuro. Se realiza hepatectomía derecha y segmentectomía hepática IVa. Evoluciona con mejoría del cuadro ictérico y el resultado anatomopatológico informa lesión vinculable a parasitosis hepática. Conclusión. Ante la presencia de un tumor hepático sólido, es necesario descartar etiología maligna de la lesión. Si no es posible descartar esto, o si el paciente persiste con sintomatología, la resección quirúrgica está indicada, teniendo en cuenta el volumen de la glándula hepática y del remanente hepático futuro.

Schistosomal liver fibrosis and hepatocellular carcinoma - case series of patients submitted to liver transplantation

ABSTRACT Schistosomiasis affects approximately 207 million people in 76 countries. The association between hepatocellular carcinoma and Schistosoma mansoni infection has been investigated. Studies using animal models suggest that the parasite may accelerate the oncogenic process when combined with other factors, such as hepatitis C virus infection or exposure to a carcinogen. Herein, we report a case series of six hepatocellular carcinoma patients from Northeast Brazil, with negative serology for both hepatitis B and C virus, submitted to liver transplantation, whose explant showed evidence of schistosomal liver fibrosis. Since all patients enrolled in this study were submitted to liver transplantation, we were able to access the whole explanted liver and perform histopathological analysis, which is often not possible in other situations. Although 50% of them showed signs of liver failure, no cirrhosis or any liver disease other than schistosomal fibrosis had been detected. These uncommon findings suggest that Schistosoma mansoni infection might predispose to hepatocellular carcinoma development, regardless of the absence of other risk factors.

Schistosomal liver fibrosis and hepatocellular carcinoma - case series of patients submitted to liver transplantation.

Schistosomiasis affects approximately 207 million people in 76 countries. The association between hepatocellular carcinoma and Schistosoma mansoni infection has been investigated. Studies using animal models suggest that the parasite may accelerate the oncogenic process when combined with other factors, such as hepatitis C virus infection or exposure to a carcinogen. Herein, we report a case series of six hepatocellular carcinoma patients from Northeast Brazil, with negative serology for both hepatitis B and C virus, submitted to liver transplantation, whose explant showed evidence of schistosomal liver fibrosis. Since all patients enrolled in this study were submitted to liver transplantation, we were able to access the whole explanted liver and perform histopathological analysis, which is often not possible in other situations. Although 50% of them showed signs of liver failure, no cirrhosis or any liver disease other than schistosomal fibrosis had been detected. These uncommon findings suggest that Schistosoma mansoni infection might predispose to hepatocellular carcinoma development, regardless of the absence of other risk factors.

Negative serology of Fasciola hepatica infection in patients with liver cancer in Peru: a preliminary report.

INTRODUCTION: The etiology of several hepatocellular carcinoma (HCC) cases remains largely unknown. Although Fasciola hepatica has been associated with liver fibrosis in Latin America, it has not yet been associated with HCC. This study aimed to determine the existence of specific IgG antibodies against F. hepatica in the serum samples of HCC patients. METHODS: In total, 13 serum samples from 13 HCC patients were screened using Fas2-ELISA. RESULTS: Fas2-ELISA demonstrated negative results in all HCC patients included in this study. CONCLUSIONS: The pre-existence of F. hepatica infection in HCC patients needs to be further investigated in epidemiological and experimental studies.

Negative serology of Fasciola hepatica infection in patients with liver cancer in Peru: a preliminary report

Abstract INTRODUCTION: The etiology of several hepatocellular carcinoma (HCC) cases remains largely unknown. Although Fasciola hepatica has been associated with liver fibrosis in Latin America, it has not yet been associated with HCC. This study aimed to determine the existence of specific IgG antibodies against F. hepatica in the serum samples of HCC patients. METHODS In total, 13 serum samples from 13 HCC patients were screened using Fas2-ELISA. RESULTS Fas2-ELISA demonstrated negative results in all HCC patients included in this study. CONCLUSIONS The pre-existence of F. hepatica infection in HCC patients needs to be further investigated in epidemiological and experimental studies.

Effect of miR-182 on hepatic fibrosis induced by Schistosomiasis japonica by targeting FOXO1 through PI3K/AKT signaling pathway.

The study aimed to investigate the impact of miR-182 and FOXO1 on S. japonica-induced hepatic fibrosis. Microarray analysis was performed to screen out differential expressed miRNAs and mRNAs. Rat hepatic fibrosis model and human hepatocellular cell line LX-2 were used to study the effect of miR-182 and FOXO1. qRT-PCR and Western blot were used to detect the expression of miR-182, FOXO1 or other fibrosis markers. The targeting relationship between FOXO1 and miR-182 was verified by luciferase reporter assay. Immunohistochemistry or immunofluorescence staining was conducted to detect FOXO1 or α-SMA in rat hepatic tissues. Cell viability and apoptosis were detected by MTT assay and flow cytometry. The expression of PI3K/AKT pathway-related proteins was detected by Western blot. miR-182 was highly expressed in liver fibrosis samples, and FOXO1 expression was negatively correlated with miR-182 expression. After transfection of miR-182, FOXO1 expression was down-regulated, with the results of LX-2 cells proliferation inhibition and apoptosis induction, as well as the aggravation of rat hepatic fibrosis. The expression of p-AKT/AKT and p-S6/S6 was increased, meaning that the PI3K/AKT signal pathway was activated. The results were reversed when treated with Wortmannin (PI3K inhibitor). After transfection of miR-182 inhibitor, FOXO1 expression was up-regulated, LX-2 cell proliferation was inhibited, and apoptosis rate was increased. High-expressed miR-182 and low-expressed FOXO1 promoted proliferation and inhibiting apoptosis on liver fibrosis cells, stimulating the development of S. japonica-induced hepatic fibrosis through feeding back to PI3K/AKT signaling pathway.

[Food-borne trematodiases]. / Trématodoses alimentaires.

Food-borne trematodiases (flukes) are transmitted through the consumption of contaminated undercooked aquatic food. Infections are most prevalent in Southeast Asia and Latin America, but might occur anywhere due to food trade, international travel, human migration. Clinical manifestations are hepatobiliary, intestinal, and pleuropulmonary. The worse complication is development of cholangiocarcinoma. Efficacious drug therapy are available, however prevention control measures are essential to avoid transmission. Since 2015, trematodiases are included in the WHO program implemented to fight neglected tropical diseases.

Les trématodoses (ou distomatoses) alimentaires sont des parasitoses transmises par la consommation de poissons, crustacés et mollusques d'eau douce. Les infections sont prévalentes en Asie et en Amérique latine. L'acquisition est liée aux habitudes culinaires impliquant la consommation d'aliments aquatiques insuffisamment ou non cuits. De nos jours, des cas d'infection peuvent se présenter dans des populations issues ou résidant dans des zones non endémiques, en raison de la globalisation du marché, du développement de l'aquaculture, de la migration des populations, et des voyages internationaux. Les manifestations cliniques sont hépatobiliaires, digestives ou pleuropulmonaires. La complication la plus redoutable est l'évolution vers le cholangiocarcinome. Depuis 2015, les trématodoses font partie du plan de lutte de l'OMS contre les maladies négligées tropicales.

Human liver flukes.

Liver fluke infections occur in people worldwide. In some low-income regions, a combination of ecological, agricultural, and culinary factors leads to a very high prevalence of infection but, in higher-income regions, infections are uncommon. Infection is associated with substantial morbidity and several liver fluke species are recognised as biological carcinogens. Here, we review the epidemiology, clinical significance, and diagnostic and treatment strategies of human infection with these pathogens.

Clonorchis sinensis granulin: identification, immunolocalization, and function in promoting the metastasis of cholangiocarcinoma and hepatocellular carcinoma.

BACKGROUND: Long-term infections by Clonorchis sinensis are associated with cholangitis, cholecystitis, liver fibrosis, cirrhosis, and even liver cancer. Molecules from the worm play vital roles in disease progress. In the present study, we identified and explored molecular characterization of C. sinensis granulin (CsGRN), a growth factor-like protein from C. sinensis excretory/secretory products (CsESPs). METHODS: The encoding sequence and conserved domains of CsGRN were identified and analysed by bioinformatics tools. Recombinant CsGRN (rCsGRN) protein was expressed in Escherichia coli BL21 (DE3). The localisation of CsGRN in adult worms and Balb/c mice infected with C. sinensis was investigated by immunofluorescence and immunohistochemistry, respectively. Stable CsGRN-overexpressed cell lines of hepatoma cells (PLC-GRN cells) and cholangiocarcinoma cells (RBE-GRN cells) were constructed by transfection of eukaryotic expression plasmid of pEGFP-C1-CsGRN. The effects on cell migration and invasion of CsGRN were assessed through the wound-healing assay and transwell assay. The levels of matrix metalloproteinase 2 and 9 (MMP2 and MMP9) in PLC-GRN or RBE-GRN cells were detected by real-time PCR (qRT-PCR). The levels of E-cadherin, vimentin, N-cadherin, zona occludens proteins (ZO-1), ß-catenin, phosphorylated ERK (p-ERK) and phosphorylated AKT (p-AKT) were analysed by Western blotting. RESULTS: CsGRN, including the conserved GRN domains, was confirmed to be a member of the granulin family. CsGRN was identified as an ingredient of CsESPs. CsGRN was localised in the tegument and testes of the adult worm. Furthermore, it appeared in the cytoplasm of hepatocytes and biliary epithelium cells from infected Balb/c mouse. The enhancement of cell migration and invasion of PLC-GRN and RBE-GRN cells were observed. In addition, CsGRN upregulated the levels of vimentin, N-cadherin, ß-catenin, MMP2 and MMP9, while it downregulated the level of ZO-1 in PLC-GRN/RBE-GRN cells. In total proteins of liver tissue from rCsGRN immunised Balb/c mice, vimentin level decreased, while E-cadherin level increased when compared with the control groups. Meanwhile, the levels of p-ERK reached a peak at 4 weeks post immunisation and the level of p-AKT did at 2 weeks after immunisation. CONCLUSIONS: The encoding sequence and molecular characteristics of CsGRN were identified. As a member of granulin superfamily, CsGRN induced mesenchymal characteristics of PLC and RBE cells and was found to regulate the activities of the downstream molecules of the ERK and PI3K/AKT signalling pathways, which could contribute to the enhancement of cell migration and invasion.

Plasmodium parasite as an effective hepatocellular carcinoma antigen glypican-3 delivery vector.

We have previously demonstrated that malaria parasite infection has an anti-tumor effect in a mouse model. This research aimed to investigate the possibility of using Plasmodium parasite as a novel vaccine vector for hepatocellular carcinoma (HCC) immunotherapy. We constructed a Plasmodium yoelii 17XNL strain (P.y) expressing murine glypican-3 (GPC3) protein (P.y-GPC3), and examined its therapeutic potency in a murine Hepa1-6-induced hepatoma model that highly expressed GPC3 protein. The prerequisites for invoking a CD8+ T cell response were assessed after P.y-based immunization, which included obviously increased concentrations of T helper cell type 1 (Th1)-associated cytokines, such as IL-2, IFN-γ and TNF-α, in serum and preferential expansion of the CD8α+ dendritic cell (DC) subset with higher expression of CD80 and CD86 molecules. Compared with uninfected and wild-type P.y-infected mice, a significant GPC3-specific cytotoxic T lymphocyte (CTL) response was detected in P.y-GPC3 vaccinated mice. Furthermore, P.y-GPC3-based vaccination dramatically inhibited Hepa1-6-induced tumor growth in the implanted HCC and prolonged the survival of tumor-bearing mice. We concluded that a Plasmodium-based vector is highly efficient in inducing tumor antigen-specific T cell-mediated immunity and protection against tumor cells. More broadly, this strategy supported our hypothesis that Plasmodium parasites, as novel therapeutic antigen vectors, may be applicable to tumor immunotherapy for patients with HCC.

Gross, histopathological and immunohistochemical study on strobilocercus of Taenia taeniaeformis infection in the liver of laboratory rats (Rattus norvegicus) in India.

We report the detailed gross, histopathological and immunohistochemical study of Strobilocercus fasciolaris infection, the metacestodal stage of Taenia taeniaeformis, in the liver of laboratory Wistar rats. Necropsy examination of seventeen rats revealed transparent or white or cream to clear, thick walled cysts, 1 to 97 in number, measuring about 2mm to 12mm on one or many of the liver lobes and containing strobilocercus of Taenia taeniaeformis. Histopathological examination revealed the presence of the cross-section of larva surrounded by a thick fibrous capsule and moderate infiltration of lymphocytes, plasma cells and a few eosinophils. Fatty degeneration of hepatocytes, gastric mucosal hyperplasia, distended gastric glands and marked increase in the mucosal epithelial cells and goblet cells in the duodenum were also observed. Contamination of feed and bedding materials seems to be the probable source in these naturally infected rats.

The rodent malaria liver stage survives in the rapamycin-induced autophagosome of infected Hepa1-6 cells.

It has been reported that non-selective autophagy of infected hepatocytes could facilitate the development of malaria in the liver stage, but the fate of parasites following selective autophagy of infected hepatocytes is still not very clear. Here, we confirmed that sporozoite infection can induce a selective autophagy-like process targeting EEFs (exo-erythrocytic forms) in Hepa1-6. Rapamycin treatment greatly enhanced this process in EEFs and non-selective autophagy of infected Hepa1-6 cells and enhanced the development of the malaria liver stage in vivo. Although rapamycin promoted the fusion of autophagosomes containing the malaria parasite with lysosomes, some parasites inside the autophagosome survived and replicated normally. Further study showed that the maturation of affected autolysosomes was greatly inhibited. Therefore, in addition to the previously described positive role of rapamycin-induced nonselective autophagy of hepatocytes, we provide evidence that the survival of EEFs in the autophagosome of the infected hepatocytes also contributes to rapamycin-enhanced development of the malaria liver stage, possibly due to the suppression of autolysosome maturation by EEFs. These data suggest that the inhibition of autolysosome maturation might be a novel escape strategy used by the malaria liver stage.

Earthworm-mediated synthesis of silver nanoparticles: A potent tool against hepatocellular carcinoma, Plasmodium falciparum parasites and malaria mosquitoes.

The development of parasites and pathogens resistant to synthetic drugs highlighted the needing of novel, eco-friendly and effective control approaches. Recently, metal nanoparticles have been proposed as highly effective tools towards cancer cells and Plasmodium parasites. In this study, we synthesized silver nanoparticles (EW-AgNP) using Eudrilus eugeniae earthworms as reducing and stabilizing agents. EW-AgNP showed plasmon resonance reduction in UV-vis spectrophotometry, the functional groups involved in the reduction were studied by FTIR spectroscopy, while particle size and shape was analyzed by FESEM. The effect of EW-AgNP on in vitro HepG2 cell proliferation was measured using MTT assays. Apoptosis assessed by flow cytometry showed diminished endurance of HepG2 cells and cytotoxicity in a dose-dependent manner. EW-AgNP were toxic to Anopheles stephensi larvae and pupae, LC(50) were 4.8 ppm (I), 5.8 ppm (II), 6.9 ppm (III), 8.5 ppm (IV), and 15.5 ppm (pupae). The antiplasmodial activity of EW-AgNP was evaluated against CQ-resistant (CQ-r) and CQ-sensitive (CQ-s) strains of Plasmodium falciparum. EW-AgNP IC(50) were 49.3 µg/ml (CQ-s) and 55.5 µg/ml (CQ-r), while chloroquine IC(50) were 81.5 µg/ml (CQ-s) and 86.5 µg/ml (CQ-r). EW-AgNP showed a valuable antibiotic potential against important pathogenic bacteria and fungi. Concerning non-target effects of EW-AgNP against mosquito natural enemies, the predation efficiency of the mosquitofish Gambusia affinis towards the II and II instar larvae of A. stephensi was 68.50% (II) and 47.00% (III), respectively. In EW-AgNP-contaminated environments, predation was boosted to 89.25% (II) and 70.75% (III), respectively. Overall, this research highlighted the EW-AgNP potential against hepatocellular carcinoma, Plasmodium parasites and mosquito vectors, with little detrimental effects on mosquito natural enemies.

Laparoscopic hepatectomy by curettage and aspiration: a report of 855 cases.

BACKGROUND: In 1998, the technique of laparoscopic hepatectomy by curettage and aspiration was developed and a special instrument, laparoscopic multifunctional operative dissector (LPMOD), was designed for this procedure. In the past 17 years, this procedure was developed gradually and had become the routine procedure for laparoscopic hepatectomy in local area. This paper is to report results of 17-year practice of this procedure. METHODS: Patients who underwent laparoscopic hepatectomy from August 1998 to March 2015 were reviewed. Hepatectomies were performed using the technique of laparoscopic hepatectomy by curettage and aspiration. By using the LPMOD, liver parenchyma was crashed and aspirated immediately and the intrahepatic ducts and small vessels were preserved and were safely dissected for ligation. Laparoscopic selective hepatic flow occlusion was performed routinely for hemi-hepatectomies to control intraoperative blood loss. RESULTS: A total of 855 cases underwent laparoscopic hepatectomy by curettage and aspiration. No perioperative death, 105 patients were converted to open operation, and 84 of them were converted before liver transection without any emergency. Postoperative bleeding occurred in three patients (0.4 %), and bile leakage occurred in seven patients (0.8 %). CONCLUSION: Laparoscopic hepatectomy by curettage and aspiration is a safe procedure for liver resection with acceptable morbidity and mortality.