An investigation of the prevalence and diversity of Anisakis in China: marine food safety implications.

Anisakis can cause Anisakiasis in humans if raw or undercooked fish is consumed. Symptoms of infection may include vomiting, acute abdominal symptoms, or allergies. In this study, we collected 187 commercially available marine fish from the Yellow Sea, East China Sea, and South China Sea. Among them, 79 were found positive containing 520 Anisakis worms. The average prevalence rate was found 42% in this investigation. Ninety-two worms from different sea areas were selected and analyzed for identification, revealing the presence of five different species, which are Anisakis pegreffii, Hysterothylacium aduncum, Hysterothylacium zhoushanense, Hysterothylacium amoyense, and Hysterothylacium sp. In the meta-analysis, three databases: PubMed, CNKI, and BaiduXueshu were searched for surveys on the prevalence of Anisakis in Chinese waters from January 2000 to December 2023. A total of 26 studies were included in this analysis of which 25 publications were retrieved from different databases and one being the present study. The pooled prevalence of Anisakis was 45% among commercially available marine fish. Variances in the prevalence of Anisakis were noted among the four seas, with the highest rates in the East China Sea and the Bohai Sea, reaching 53% [0.38; 0.68] and 49% [0.36; 0.62], respectively. The Prevalence of Anisakis infection was significantly higher in astern parts such as Liaoning, Shanghai, and Zhejiang. Analysis of the host fish subgroups revealed that the orders of Anguilliformes, Scombriformes, and Gadiformes had high rates of infection. These findings suggest a significant prevalence of Anisakis, posing an increasing risk of infection for individuals. This study provides impactful information for implementing preventative measures against Anisakis.

TERT accelerates BRAF mutant-induced thyroid cancer dedifferentiation and progression by regulating ribosome biogenesis.

TERT reactivation occurs frequently in human malignancies, especially advanced cancers. However, in vivo functions of TERT reactivation in cancer progression and the underlying mechanism are not fully understood. In this study, we expressed TERT and/or active BRAF (BRAF V600E) specifically in mouse thyroid epithelium. While BRAF V600E alone induced papillary thyroid cancer (PTC), coexpression of BRAF V600E and TERT resulted in poorly differentiated thyroid carcinoma (PDTC). Spatial transcriptome analysis revealed that tumors from mice coexpressing BRAF V600E and TERT were highly heterogeneous, and cell dedifferentiation was positively correlated with ribosomal biogenesis. Mechanistically, TERT boosted ribosomal RNA (rRNA) expression and protein synthesis by interacting with multiple proteins involved in ribosomal biogenesis. Furthermore, we found that CX-5461, an rRNA transcription inhibitor, effectively blocked proliferation and induced redifferentiation of thyroid cancer. Thus, TERT promotes thyroid cancer progression by inducing cancer cell dedifferentiation, and ribosome inhibition represents a potential strategy to treat TERT-reactivated cancers.

Why is Babesia not killed by artemisinin like Plasmodium?

Babesia spp. are intraerythrocytic apicomplexans that digest and utilize red blood cells in a similar way to intraerythrocytic Plasmodium spp., but unlike the latter, are not sensitive to artemisinin. A comparison of Babesia and Plasmodium genomes revealed that Babesia genomes, which are smaller than those of Plasmodium, lack numerous genes, and especially haem synthesis-related genes, that are found in the latter. Single-cell sequencing analysis showed that the different treatment groups of Babesia microti with expressed pentose phosphate pathway-related, DNA replication-related, antioxidation-related, glycolysis-related, and glutathione-related genes were not as sensitive to artemether as Plasmodium yoelii 17XNL. In particular, pentose phosphate pathway-related, DNA replication-related, and glutathione-related genes, which were actively expressed in P. yoelii 17XNL, were not actively expressed in B. microti. Supplying iron in vivo can promote the reproduction of B. microti. These results suggest that Babesia spp. lack a similar mechanism to that of malaria parasites through which the haem or iron in hemoglobin is utilized, and that this likely leads to their insensitivity to artemisinin.

Dynamic miRNA profile of host T cells during early hepatic stages of Schistosoma japonicum infection.

Schistosomes undergo complicated migration in final hosts during infection, associated with differential immune responses. It has been shown that CD4+ T cells play critical roles in response to Schistosoma infections and accumulated documents have indicated that miRNAs tightly regulate T cell activity. However, miRNA profiles in host T cells associated with Schistosoma infection remain poorly characterized. Therefore, we undertook the study and systematically characterized T cell miRNA profiles from the livers and blood of S. japonicum infected C57BL/6J mice at 14- and 21-days post-infection. We observed 508 and 504 miRNAs, in which 264 miRNAs were co-detected in T cells isolated from blood and livers, respectively. The comparative analysis of T cell miRNAs from uninfected and infected C57BL/6J mice blood showed that miR-486b-5p/3p expression was significantly downregulated and linked to various T cell immune responses and miR-375-5p was highly upregulated, associated with Wnt signaling and pluripotency, Delta notch signaling pathways, etc. Whereas hepatic T cells showed miR-466b-3p, miR-486b-3p, miR-1969, and miR-375 were differentially expressed compared to the uninfected control. The different expressions of some miRNAs were further corroborated in isolated T cells from mice and in vitro cultured EL-4 cells treated with S. japonicum worm antigens by RT-qPCR and similar results were found. In addition, bioinformatics analysis combined with RT-qPCR validation of selected targets associated with the immune system and parasite-caused infectious disease showed a significant increase in the expression of Ctla4, Atg5, Hgf, Vcl and Arpc4 and a decreased expression of Fermt3, Pik3r1, Myd88, Nfkbie, Ppp1r12a, Ppp3r1, Nfyb, Atg12, Ube2n, Tyrobp, Cxcr4 and Tollip. Overall, these results unveil the comprehensive repertoire of T cell miRNAs during S. japonicum infection, suggesting that the circulatory (blood) and liver systems have distinct miRNAs landscapes that may be important for regulating T cell immune response. Altogether, our findings indicated a dynamic expression pattern of T cell miRNAs during the hepatic stages of S. japonicum infection.

Genome-wide identification of circular RNAs in adult Schistosoma japonicum.

Circular RNAs (circRNAs) are a class of novel, widespread, covalently closed RNAs that have played an essential role in animal gene regulation. To systematically explore circRNAs in the blood fluke Schistosoma japonicum, we performed RNA sequencing and bioinformatics analysis, and found that hundreds of circRNAs showed gender-associated expression. Among these identified circRNAs, more than 77.54% and 74.73% were putatively derived from the exon region of the genome and some circRNAs showed gender-associated expressions. The functional prediction of circRNAs (circ_003826 and circ_004690) showed potential binding sites and possibly acted as the sponge to regulate microRNAs (miRNAs) sja-miR-1, sja-miR-133 and sja-miR-3504. Altogether, these findings demonstrated that S. japonicum also contains circRNAs, which may have potential regulatory roles during schistosome development.

The Positive Role and Mechanism of Herbal Medicine in Parkinson's Disease.

Parkinson's disease (PD) is a complex neurodegenerative disease, manifested by the progressive functional impairment of the midbrain nigral dopaminergic neurons. Due to the unclear underlying pathogenesis, disease-modifying drugs for PD remain elusive. In Asia, such as in China and India, herbal medicines have been used in the treatment of neurodegenerative disease for thousands of years, which recently attracted considerable attention because of the development of curative drugs for PD. In this review, we first summarized the pathogenic factors of PD including protein aggregation, mitochondrial dysfunction, ion accumulation, neuroinflammation, and oxidative stress, and the related recent advances. Secondly, we summarized 32 Chinese herbal medicines (belonging to 24 genera, such as Acanthopanax, Alpinia, and Astragalus), 22 Chinese traditional herbal formulations, and 3 Indian herbal medicines, of which the ethanol/water extraction or main bioactive compounds have been extensively investigated on PD models both in vitro and in vivo. We elaborately provided pictures of the representative herbs and the structural formula of the bioactive components (such as leutheroside B and astragaloside IV) of the herbal medicines. Also, we specified the potential targets of the bioactive compounds or extractions of herbs in view of the signaling pathways such as PI3K, NF-κB, and AMPK which are implicated in oxidative and inflammatory stress in neurons. We consider that this knowledge of herbal medicines or their bioactive components can be favorable for the development of disease-modifying drugs for PD.

Site-Selective Phosphoglycerate Mutase 1 Acetylation by a Small Molecule.

Post-translational modifications play vital roles in fine-tuning a myriad of physiological processes, and one of the most important modifications is acetylation. Here, we report a ligand-directed site-selective acetylation using KHAc, a derivative of a phosphoglycerate mutase 1 (PGAM1) inhibitor. KHAc binds to PGAM1 and transfers its acetyl group to the ε-NH2 of Lys100 to inactivate the enzyme. The acetyl transfer process was visualized by time-resolved crystallography, demonstrating that the transfer is driven by proximity effects. KHAc was capable of selectively and effectively acetylating Lys100 of PGAM1 in cultured human cells, accompanied by inhibited F-actin formation. Similar strategies could be used for exogenous control of other lysine post-translational modifications.

An alternatively transcribed TAZ variant negatively regulates JAK-STAT signaling.

Type I interferon (IFN)-induced Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling drives the expression of IFN-stimulated genes (ISGs) to mediate antiviral response. The strength and duration of JAK-STAT signaling are tightly regulated to ensure effective antiviral defense while avoiding pathological inflammation and autoimmunity. Here, we report that cTAZ, an isoform of the Hippo pathway effector TAZ, is transcribed by an alternative promoter. Although majority of C-terminal sequences of TAZ is retained, cTAZ is not regulated by the Hippo signaling and does not mediate its growth-inhibitory functions. Instead, cTAZ negatively regulates JAK-STAT signaling by inhibiting STAT1/2 nuclear localization and ISG expression, and its expression is induced by type I IFN Thus, cTAZ functions as a modulator of JAK-STAT signaling and may play a role in fine-tuning cellular antiviral response.

The aberrantly expressed miR-193b-3p contributes to preeclampsia through regulating transforming growth factor-ß signaling.

Preeclampsia (PE) is a leading cause of maternal mortality worldwide. Several studies have detected some differentially expressed microRNAs in the preeclamptic placenta, but few of the identified microRNAs demonstrated consistent findings among different research studies. In this study, high-throughput microRNA sequencing (HTS) of 9 preeclamptic and 9 normal placentas was performed. Seventeen microRNAs were identified to be up-regulated, and 8 down-regulated in preeclamptic placentas. Eight differentially expressed microRNAs except one identified in our study were determined to be consistent with at least one previous study, while sixteen were newly found. We performed qRT-PCR with independent 22 preeclamptic placentas and 20 control placentas to verify the differentially expressed microRNAs, and ten microRNAs were validated. The predicted target genes of the aberrantly expressed miR-193b-3p were enriched in the following gene ontology categories: cell motility and migration, cell proliferation and angiogenesis. We also found that miR-193b-3p significantly decreased the migration and invasion of trophoblast (HTR-8/SVneo) cells and that miR-193b-3p could regulate trophoblasts migration and invasion through binding onto the 3'UTR target site of TGF-ß2. In conclusion, we identified a list of differentially expressed microRNAs in PE placentas by HTS and provided preliminary evidence for the role of miR-193b-3p in the pathogenesis of preeclampsia.