Hepatic progenitor cells promote the repair of schistosomiasis liver injury by inhibiting IL-33 secretion in mice.

BACKGROUND: Hepatic schistosomiasis, a chronic liver injury induced by long-term Schistosoma japonicum (S. japonicum) infection, is characterized by egg granulomas and fibrotic pathology. Hepatic progenitor cells (HPCs), which are nearly absent or quiescent in normal liver, play vital roles in chronic and severe liver injury. But their role in the progression of liver injury during infection remains unknown. METHODS: In this study, the hepatic egg granulomas, fibrosis and proliferation of HPCs were analyzed in the mice model of S. japonicum infection at different infectious stages. For validating the role of HPCs in hepatic injury, tumor necrosis factor-like-weak inducer of apoptosis (TWEAK) and TWEAK blocking antibody were used to manipulate the proliferation of HPCs in wild-type and IL-33-/- mice infected with S. japonicum. RESULTS: We found that the proliferation of HPCs was accompanied by inflammatory granulomas and fibrosis formation. HPCs expansion promoted liver regeneration and inhibited inflammatory egg granulomas, as well as the deposition of fibrotic collagen. Interestingly, the expression of IL-33 was negatively associated with HPCs' expansion. There were no obvious differences of liver injury caused by infection between wild-type and IL-33-/- mice with HPCs' expansion. However, liver injury was more attenuated in IL-33-/- mice than wild-type mice when the proliferation of HPCs was inhibited by anti-TWEAK. CONCLUSIONS: Our data uncovered a protective role of HPCs in hepatic schistosomiasis in an IL-33-dependent manner, which might provide a promising progenitor cell therapy for hepatic schistosomiasis.

Human coronaviruses and therapeutic drug discovery.

BACKGROUND: Coronaviruses (CoVs) are distributed worldwide and have various susceptible hosts; CoVs infecting humans are called human coronaviruses (HCoVs). Although HCoV-specific drugs are still lacking, many potent targets for drug discovery are being explored, and many vigorously designed clinical trials are being carried out in an orderly manner. The aim of this review was to gain a comprehensive understanding of the current status of drug development against HCoVs, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MAIN TEXT: A scoping review was conducted by electronically searching research studies, reviews, and clinical trials in PubMed and the CNKI. Studies on HCoVs and therapeutic drug discovery published between January 2000 and October 2020 and in English or Chinese were included, and the information was summarized. Of the 3248 studies identified, 159 publication were finally included. Advances in drug development against HCoV, especially SARS-CoV-2, are summarized under three categories: antiviral drugs aimed at inhibiting the HCoV proliferation process, drugs acting on the host's immune system, and drugs derived from plants with potent activity. Furthermore, clinical trials of drugs targeting SARS-CoV-2 are summarized. CONCLUSIONS: During the spread of COVID-19 outbreak, great efforts have been made in therapeutic drug discovery against the virus, although the pharmacological effects and adverse reactions of some drugs under study are still unclear. However, well-designed high-quality studies are needed to further study the effectiveness and safety of these potential drugs so as to provide valid recommendations for better control of the COVID-19 pandemic.

Gut Microbiota Modulates Intestinal Pathological Injury in Schistosoma japonicum-Infected Mice.

Trapping of Schistosoma japonicum (S. japonicum) eggs in host tissue, mainly in the intestine and liver, causes severe gastrointestinal and hepatic granulomatous immune responses and irreversible fibrosis. Although the gut microbiota plays a central role in regulating pathological responses in several diseases, the effect of the gut microbiota on the pathologenesis progression of schistosomiasis remains largely unknown. In this study, we aimed to investigate the regulatory function of the gut microbiota in schistosomiasis japonica. We found that the depletion of the gut microbiota significantly ameliorated egg granulomas formation and fibrosis in the intestine of infected mice. This role of the gut microbiota in intestinal granuloma formation and fibrosis was reinforced when normal and infected mice were housed together in one cage. Notably, changes in the gut microbiota induced by S. japonicum infection were partly reversible with microbiota transfer in the cohousing experiment. Transfer of the gut microbiota from normal to infected mice attenuated the intestinal pathological responses. Depletion of the gut microbiota by antibiotics, or transfer of the gut microbiota from normal to infected mice decreased the levels of IL-4, IL-5, and IL-13 and promoted the production of cytokines and mRNA levels of IL-10 and TGF-ß in infected mice. Our findings indicated a regulatory effect of the gut microbiota on intestinal pathological injury associated with schistosomiasis japonica in mice, and thus suggested a potential strategy for schistosomiasis treatment.

The genetic basis of adaptive evolution in parasitic environment from the Angiostrongylus cantonensis genome.

Angiostrongylus cantonensis (rat lungworm) is the etiological agent of angiostrongyliasis, mainly causing eosinophilic meningitis or meningoencephalitis in human. Although the biology of A. cantonensis is relatively well known, little is understood about the mechanisms of the parasite's development and survival in definitive hosts, or its adaptation to a broad range of snail intermediate hosts. Here, we generate a high-quality assembly of a well-defined laboratory strain of A. cantonensis from Guangzhou, China, by using Illumina and PacBio sequencing technologies. We undertake comparative analyses with representative helminth genomes and explore transcriptomic data throughout key developmental life-cycles of the parasite. We find that part of retrotransposons and gene families undergo multiple waves of expansions. These include extracellular superoxide dismutase (EC-SOD) and astacin-like proteases which are considered to be associated with invasion and survival of the parasite. Furthermore, these paralogs from different sub-clades based on phylogeny, have different expression patterns in the molluscan and rodent stages, suggesting divergent functions under the different parasitic environment. We also find five candidate convergent signatures in the EC-SOD proteins from flukes and one sub-clade of A. cantonensis. Additionally, genes encoding proteolytic enzymes, involved in host hemoglobin digestion, exhibit expansion in A. cantonensis as well as two other blood-feeding nematodes. Overall, we find several potential adaptive evolutionary signatures in A. cantonensis, and also in some other helminths with similar traits. The genome and transcriptomes provide a useful resource for detailed studies of A. cantonensis-host adaptation and an in-depth understanding of the global-spread of angiostrongyliasis.

ß-Actin: Not a Suitable Internal Control of Hepatic Fibrosis Caused by Schistosoma japonicum.

Schistosomiasis japonica is a significant health problem that leads to morbidity and mortality of humans. It is characterized by hepatic granulomatous response and fibrosis caused by eggs deposition in the liver. ß-actin, a traditional housekeeping gene, is widely used as an internal control to normalize gene and protein expression. However, ß-actin expression can fluctuate upon the treatment with pharmacological agents or under some physiological and pathological conditions. In this study, we found that the expressions of both ß-actin mRNA and protein increased significantly with hepatic fibrosis formation after 6 weeks infection with Schistosoma japonicum and kept high level during the progression of hepatic fibrosis, while the levels of ß-Tubulin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) remained stable. The dynamic change of ß-actin was similar with the profibrogenic factors, including α-SMA, Collagen I, and Collagen III. We employed immunofluorescence staining and further showed that the expression level of ß-actin was positively correlated with α-SMA. What is more, there was a positive correlation between the level of ß-actin mRNA and the content of hydroxyproline in liver. This study provides evidences that ß-actin is variable and unsatisfied for application as an internal control in hepatic fibrosis induced by S. japonicum infection.

Imported parasitic diseases in mainland China: current status and perspectives for better control and prevention.

BACKGROUND: The high prevalence of parasitic diseases leads to millions of deaths and disabilities each year in developing countries. China has also been greatly affected by parasitic infections, including filariasis, leishmaniasis, malaria, schistosomiasis, and soil-transmitted nematodosis. However, the situation in China improved dramatically after comprehensive parasitic disease control efforts were strengthened, leading to the elimination of filariasis in 2006 and to significant control over other diseases. However, imported parasitic disease cases are inevitable, and such cases have increasingly been reported as a result of enhanced globalization and international or regional cooperation. These imported diseases represent a major obstacle to the elimination of several parasitoses, such as malaria. MAIN TEXT: This paper reviews imported cases of parasitic diseases in mainland China, particularly malaria and schistosomiasis, based on data reported separately by the Chinese annual reports and from other published papers. We summarize the new challenges that face parasitic disease control efforts in mainland China and perspectives regarding better control. We argue that both the provision of professional education and updated training for medical care personnel and the management and surveillance of people entering China are essential. We recommend that Chinese migrant workers should be considered a priority group for health education and that public awareness of imported diseases should be emphasized. Furthermore, we underscore the importance of investigating the distribution of introduced/potential vectors, parasite susceptibility, and improvements in diagnostic techniques and drug stocks. CONCLUSIONS: Imported cases have become the main challenge to the elimination of several parasitoses, such as malaria and schistosomiasis, in mainland China. China should act to meet these challenges, which are closely associated with national biological safety.

Snail-borne parasitic diseases: an update on global epidemiological distribution, transmission interruption and control methods.

BACKGROUND: Snail-borne parasitic diseases, such as angiostrongyliasis, clonorchiasis, fascioliasis, fasciolopsiasis, opisthorchiasis, paragonimiasis and schistosomiasis, pose risks to human health and cause major socioeconomic problems in many tropical and sub-tropical countries. In this review we summarize the core roles of snails in the life cycles of the parasites they host, their clinical manifestations and disease distributions, as well as snail control methods. MAIN BODY: Snails have four roles in the life cycles of the parasites they host: as an intermediate host infected by the first-stage larvae, as the only intermediate host infected by miracidia, as the first intermediate host that ingests the parasite eggs are ingested, and as the first intermediate host penetrated by miracidia with or without the second intermediate host being an aquatic animal. Snail-borne parasitic diseases target many organs, such as the lungs, liver, biliary tract, intestines, brain and kidneys, leading to overactive immune responses, cancers, organ failure, infertility and even death. Developing countries in Africa, Asia and Latin America have the highest incidences of these diseases, while some endemic parasites have developed into worldwide epidemics through the global spread of snails. Physical, chemical and biological methods have been introduced to control the host snail populations to prevent disease. CONCLUSIONS: In this review, we summarize the roles of snails in the life cycles of the parasites they host, the worldwide distribution of parasite-transmitting snails, the epidemiology and pathogenesis of snail-transmitted parasitic diseases, and the existing snail control measures, which will contribute to further understanding the snail-parasite relationship and new strategies for controlling snail-borne parasitic diseases.

Case report: A rare case of urinary myiasis induced by the fourth instar larvae of Telmatoscopus albipunctatus.

Telmatoscopus albipunctatus, a cosmopolitan fly, is widely distributed throughout moist environments. It is one of the most medically important insects (especially in urban environments) that may potentially cause myiasis. Urinary myiasis and other sites of infestation, including the intestine, nasal passages, lung, and derma, have been reported. This is the first case report of a Chinese middlescent woman infected with T. albipunctatus in Guangzhou, China. In the present report, a 50-year-old woman came to The Third Affiliated Hospital of Southern Medical University, Guangzhou, China, because larvae were found when urinating in the morning; this had occurred every two days within the past two months. She complained of frequent micturition and urgency. Urine tests indicated that all indexes were normal except for slight urinary tract infection. Subsequently, the larvae were sent to the diagnostic section for parasitic infection in the Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. The stereoscopic microscope and transmission electron microscope were used for morphological observation. On this basis, the cytochrome oxidase subunit 1 (COX1) gene was specifically amplified by PCR. Sequence analysis of the PCR product and phylogenetic analysis were used to identify the species. Morphological analysis combined with molecular biology methods indicated that the insect was the fourth instar larvae of T. albipunctatus. Our results show that this was a case of a 50-year-old woman infected with T. albipunctatus larvae in her urinary tract, and the findings suggest that clinicians should be vigilant for this infection.

Parasitology should not be abandoned: data from outpatient parasitological testing in Guangdong, China.

Over the past six decades, the Chinese government made parasitoses with a high disease burden, including soil-transmitted nematode infections, malaria, leishmaniasis, filariasis, and schistosomiasis, a public health priority because they were seen to be crucial impediments to the development of rural areas. As a result, these debilitating parasitic diseases that used to be widely prevalent have been well controlled or eliminated. Consequently, less attention has been paid to parasitic infection during the rapid development of the economy, especially in developed areas. However, our investigations conducted in the parasitological laboratory of Sun Yat-sen University (Guangzhou, Guangdong, China) show that emerging parasitic diseases still threaten many people's health, with 340 of 880 outpatients (38.6%) receiving a diagnosis of parasitic disease, among whom 201 (59.1%) had clonorchiasis and 120 (35.3%) had taeniasis/cysticercosis. Furthermore, our doctors are not equipped with sufficient parasitology knowledge because this discipline is not able to maintain attraction. Many parasitic infections that result in severe consequences are treatable and preventable, but the phenomena of misdiagnosis and missed diagnosis are common and merit attention.

A cross-sectional survey comparing a free treatment program for advanced schistosomiasis japonica to a general assistance program.

The prevalence and intensity of schistosomiasis has dropped dramatically in China due to an effective integrated control program. However, advanced schistosomiasis is becoming a key challenge on the road to elimination. The aims of this study were to compare the disease condition between advanced cases under the general assistance program (GAP) and free treatment program (FTP) and to determine whether the FTP should be popularized to provide an objective reference for policymakers in China's advanced schistosomiasis control program. One hundred and ninety-four patients with schistosomiasis japonica who were enrolled in the GAP or FTP participated in this study. Little significant difference was observed in the potential confounders, including general characteristics, comorbidities, and lifestyle, indicating a similar effect on the pathology of liver damage caused by schistosome infection. There was no apparent difference in the incidence of common clinical symptoms. Furthermore, no significant difference was observed in the ultrasound findings, implying that the GAP and FTP groups shared a similar degree of liver lesion. With the exception of the abnormal rates of aspartate aminotransferase (AST), alkaline phosphatase (ALP), and hyaluronic acid (HA), the other serological indicators were comparable between the groups. Overall, the FTP is not a better option for controlling advanced schistosomiasis in China. It is important to reveal the precise mechanism underlying the pathogenesis of advanced schistosomiasis so that specific approaches to treating and preventing the development of advanced schistosomiasis can be developed and schistosomiasis can be eliminated in China.

Lessons from a 15-year-old boy with advanced schistosomiasis japonica in China: a case report.

Schistosomiasis is a chronic, parasitic disease caused by flukes (trematodes) of the genus Schistosoma, which presents the most important global burden of the 17 neglected tropical diseases listed by the World Health Organization. China has made great achievements in schistosomiasis control, and now China is planning to move forward, to eliminate schistosomiasis within 2020, but the fact cannot be denied that the possibility of schistosome infection is still there in some endemic due to its zoonotic nature as well as wide distribution of its intermediate hosts (snails). Thus, how to interrupt the transmission in areas with distribution of schistosomes and intermediate snails becomes a very serious challenge that China is facing. In this paper, it is reported an advanced schistosomiasis japonica case of a 15-year-old boy which is extremely rare in the current schistosomiasis control in China. Thus, it is supposed to strengthen health education of school children and to train professional physicians of local hospitals.

History of schistosomiasis epidemiology, current status, and challenges in China: on the road to schistosomiasis elimination.

Schistosomiasis is a snail-borne disease caused by worms of the genus Schistosoma. Worldwide, human schistosomiasis remains a serious public health problem, threatening ∼800 million people in 78 countries with a loss of 70 million disability-adjusted life years. Schistosoma japonicum is the only human blood fluke that occurs in China. As one of the countries suffering greatly from schistosomiasis, over the past 65 years, China has made great strides in controlling schistosomiasis, blocking the transmission of S. japonicum in five provinces, remarkably reducing transmission intensities in the other seven endemic provinces, and China is currently preparing to move toward the elimination of this disease before 2025. However, while on the road to schistosomiasis elimination, emerging challenges merit attention, including severe advanced cases, increased movements of population and livestock, large-area distribution of intermediate host snails, limitations of new drug developments and no vaccine available, as well as imported schistosomiasis and its potential risk.

Assessment of the effect of treatment and assistance program on advanced patients with schistosomiasis japonica in China from 2009 to 2014.

Schistosomiasis is one of the most important zoonoses, threatening approximately 800 million people in 78 countries with a loss of 70 million disability-adjusted life years. Over the past six decades, China has made remarkable achievements in morbidity control, but disability and mortality control remains much to desire; thus, advanced schistosomiasis is a growing problem when on the road to schistosomiasis elimination. Since 2005, China has initiated a national treatment and assistance program to advanced patients, aiming to improve patients' symptoms and quality of life. Here, we conducted a two-phase study to evaluate the program's implementation and effect on advanced patients from 2009 to 2014 in Jiangxi Province, China. A total of 6425 advanced schistosomiasis cases were included in this study. For those having been treated and assisted (90.7 %), the cure or improvement rate was over 99.9 %, with 668 (11.5 %) cases having reached clinical cure and 5152 (88.4 %) cases' condition having improved, which can be partially reflected in the significant decline of the proportion of hepatomegaly (splenomegaly), the degree of liver fibrosis, ascites-related indicators (abdominal girth and frequency of shifting dullness), and portal hypertension-related indices (inner diameter of portal vein and frequency of subcutaneous varicose vein of abdominal wall). Besides, it was estimated to have saved 2004 years of life lost at total. Therefore, the government should continue support and increase input of treatment and assistance program so that this project can reach more patients, leading to consolidation of achievements of schistosomiasis control and contribution to schistosomiasis elimination.

Nucleic acid detection in the diagnosis and prevention of schistosomiasis.

Schistosomiasis is an important zoonotic parasitic disease that causes serious harms to humans and animals. Surveillance and diagnosis play key roles in schistosomiasis control, however, current techniques for surveillance and diagnosis of the disease have limitations. As genome data for parasites are increasing, novel techniques for detection incorporating nucleotide sequences are receiving widespread attention. These sensitive, specific, and rapid detection methods are particularly important in the diagnosis of low-grade and early infections, and may prove to have clinical significance. This paper reviews the progress of nucleic acid detection in the diagnosis and prevention of schistosomiasis, including such aspects as the selection of target genes, and development and application of nucleic acid detection methods.

Angiostrongylus cantonensis in the vector snails Pomacea canaliculata and Achatina fulica in China: a meta-analysis.

Angiostrongyliasis is a food-borne parasitic disease induced by the nematode Angiostrongylus cantonensis, and has been recognized as the main cause leading to human eosinophilic meningitis. Humans usually acquire infection by digestion of infected Pomacea canaliculata and Achatina fulica, the most predominant intermediate hosts found in China. This meta-analysis was aimed to assess the prevalence of A. cantonensis infection among these two snails in China in the past 10 years. Data were systematically collected in electronic databases such as PubMed, Web of Science, ScienceDirect, CNKI, SinoMed, VIP, CSCD, and Wanfang from 2005 to 2015. Thirty-eight studies with a total of 41,299 P. canaliculata and 21,138 Ac. fulica were included in the present study. The overall infection rate of A. cantonensis in China was estimated to be 7.6 % (95 % confidential interval (CI) = 0.063 to 0.090) in P. canaliculata and 21.5 % in Ac. fulica (95 % CI = 0.184 to 0.245), respectively. No significant difference was observed in prevalence rates among publication year and sample size for both snails. Also, it was found that the prevalence in Ac. fulica is significantly higher than that in P. canaliculata (odds ratio (OR) = 3.946, 95 % CI = 3.070 to 5.073). The present study reveals that snail infection with A. cantonensis is clearly prevalent in China. Further studies are required to improve strategies for control of infections of snails, particularly those of Ac. fulica, and to detect further factors and conditions such as geographic region, temperatures, and diagnosis method.

[Pathology and pathogenesis of liver fibrosis induced by Schistosoma japonicum].

Schistosomiasis is a widely distributed parasitic zoonoses that threatens human' s health and social economic development. China is one of the most endemic countries in the world. Schistosoma egg are mainly lodged in the liver and intestinal tissues. There, the eggs induce a granulomatous host immune response largely characterized by lymphocytes, eosinophils, and alternatively activated macrophages. The process of granuloma formation induces chronic inflammation that leads to liver fibrosis accompanied by obvious manifestations such as hepatosplenomegaly and ascites. In this article, we review the advanced progress in research about schistosomiasis hepatic fibrosis, including the pathology of liver fibrosis, the formation and modulation of granuloma and fibrosis, the key inflammatory factors and related signaling pathways, the regulatory role of ncRNA in the process of fibrosis, and anti-fibrosis treatment and new drugs development.

A robust and automatic method for human parasite egg recognition in microscopic images.

With the accelerated movement of population, human parasitoses become an increasingly serious public health's problem. Currently, detections of parasite eggs through microscopic images are still the golden standard for diagnoses. However, this conventional method relies heavily on the experiences of inspectors, thus giving rise to misdiagnoses and missed diagnoses occasionally. And, as the number of clinical specimens increases rapidly, manual identification seems impractical. Hence, a fully automatic method is in desperate need. In this paper, we propose a robust method to segment and recognize the parasite eggs. Their contours are extracted using phase coherence technology, and the support vector machine (SVM) method based on shape and texture features is employed to classification of parasite eggs. Our novel method was comparable to the traditional method. The overall recognition rate was up to 95%, and the overall robustness indexes, including si, fnvf, fvpf, tpvf, were 95.7, 4.9, 3.7, 95.1, respectively, suggesting that our method is effective and the robustness is good, which has great potential to become a diagnostic method in the parasitological clinic.

The expression of molecule CD28 and CD38 on CD4⁺/CD8⁺ T lymphocytes in thymus and spleen elicited by Schistosoma japonicum infection in mice model.

Schistosomiasis caused by human schistosomes such as Schistosoma japonicum (S. japonicum) is considered as an immune-related disease. It was demonstrated that specific cytokine antibodies' response elicited by S. japonicum infection was gradually downregulated with the progress of the disease, resulting in a Th1/Th2 polarization and suppression of immune response. CD28 (cluster of differentiation 28) is one of the proteins expressed on T cells that provide co-stimulatory signals required for T cell activation and survival, and CD38 is an activating marker of T lymphocyte with high expression in many acute or chronic infections. The immune signature of CD28null T cells in the peripheral circulation associates with chronic inflammation in many diseases, such as HIV and CMV infection. In the thymus, CD28 expression on developing thymocytes appears to play a role for their selection, and it synergizes with CD38 to induce apoptosis of DP (double-positive) thymocytes. Few reports about CD28 and CD38 have been published in schistosomiasis. Here, we investigated the dynamic patterns of the expression of molecules CD28 and CD38 on CD4(+)/CD8(+) T lymphocytes of the thymus and spleen in mice model with S. japonicum infection. Our data indicated that at an early period of infection, the frequency of CD8(+)CD28(-) T cell in the spleen decreased significantly, but higher at chronic infection than that in control. However, it demonstrated an increasing trend in the thymus with the progression of infection. The frequency of CD4(+)CD28(-) T cells increased from acute infection in the thymus, while from chronic infection in the spleen. The expression of CD38 on CD8(+) T cells began to increase at 4 weeks post infection both in the thymus and spleen; its elevated expression on CD4(+) T cells emerged at 6 weeks post infection in the thymus and at 10 weeks post infection in the spleen. Praziquantel (PZQ) treatment could partially restore the frequency of CD28(+) T cell of CD4(+) T cells and CD38(+) T cell of CD8(+)/CD4(+) T cells in the spleen and CD38(+) T cell in the thymus. We hypothesized that the reactivation of S. japonicum infection may trigger expansion of CD28(-) T cells and hence mediate systemic inflammation. We speculated that CD8(+)CD28(-) T cell might be involved in immune modulation and CD8(+)CD28(-) T cell may be a crucial part in pathogenesis, which can provide further knowledge of the sophisticated mechanism of immuno-downregulation in schistosomiasis and potential treatment target.

Together in the fight against neglected public health problems: worldwide network cooperation on waterborne diseases and emerging parasitic diseases.

A symposium held in Guangzhou, China, aimed to become starting point of an international cooperation in the fight against waterborne diseases, which obtain more and more importance in times of global warming and globalization.