The negatively charged aminophospholipid, phosphatidylserine (PtdSer), is located in the inner leaflet of the plasma membrane in normal cells, and may be exposed to the outer leaflet under some immune and blood coagulation processes. Meanwhile, Ptdser exposed to apoptotic cells can be recognized and eliminated by various immune cells, whereas on the surface of activated platelets Ptdser interacts with coagulation factors prompting enhanced production of thrombin which significantly facilitates blood coagulation. In the case where PtdSer fails in exposure or mistakenly occurs, there are occurrences of certain immunological and haematological diseases, such as the Scott syndrome and Systemic lupus erythematosus. Besides, viruses (e.g., Human Immunodeficiency Virus (HIV), Ebola virus (EBOV)) can invade host cells through binding the exposed PtdSer. Most recently, the Corona Virus Disease 2019 (COVID-19) has been similarly linked to PtdSer or its receptors. Therefore, it is essential to comprehensively understand PtdSer and its functional characteristics. Therefore, this review summarizes Ptdser, its eversion mechanism; interaction mechanism, particularly with its immune receptors and coagulation factors; recognition sites; and its function in immune and blood processes. This review illustrates the potential aspects for the underlying pathogenic mechanism of PtdSer-related diseases, and the discovery of new therapeutic strategies as well.

Diabetes mellitus (DM) and Parkinson’s disease (PD) have been and will continue to be two common chronic diseases globally that are difficult to diagnose during the prodromal phase. Current molecular genetics, cell biological, and epidemiological evidences have shown the correlation between PD and DM. PD shares the same pathogenesis pathways and pathological factors with DM. In addition, β-cell reduction, which can cause hyperglycemia, is a striking feature of DM. Recent studies indicated that hyperglycemia is highly relevant to the pathologic changes in PD. However, further correlation between DM and PD remains to be investigated. Intriguingly, polycystic monoamine transporter 2 (VMAT2), which is co-expressed in dopaminergic neurons and β cells, is responsible for taking up dopamine into the presynaptic vesicles and can specifically bind to the β cells. Furthermore, we have summarized the specific molecular and diagnostic functions of VMAT2 for the two diseases reported in this review. Therefore, VMAT2 can be applied as a target probe for positron emission tomography (PET) imaging to detect β-cell and dopamine level changes, which can contribute to the diagnosis of DM and PD during the prodromal phase. Targeting VMAT2 with the molecular probe 18 F-FP-(+)-DTBZ can be an entry point for the β cell mass (BCM) changes in DM at the molecular level, to clarify the potential relationship between DM and PD. VMAT2 has promising clinical significance in investigating the pathogenesis, early diagnosis, and treatment evaluation of the two diseases.

Existing diagnostic methods are limited to observing appearance and demeanor, even though genetic factors play important roles in the pathology of schizophrenia. Indeed, no molecular-level test exists to assist diagnosis, which has limited treatment strategies. To address this serious shortcoming, we used a bioinformatics approach to identify 61 genes that are differentially expressed in schizophrenia patients compared with healthy controls. In particular, competing endogenous RNA network revealed the important role of the gene RASD2 , which is regulated by miR-4763-3p. Indeed, analysis of blood samples confirmed that RASD2 is downregulated in schizophrenia patients. Moreover, positron emission tomography data collected for 44 human samples identified the prefrontal and temporal lobes as potential key brain regions in schizophrenia patients. Mechanistic studies indicated that miR-4763-3p inhibits RASD2 by base-pairing with the 3’ untranslated region of RASD2 mRNA. Importantly, RASD2 has been shown to interact with β-arrestin2 , which contributes to the regulation of the DRD2-dependent CREB response element-binding protein pathway in the dopamine system. Finally, results obtained with a mouse model of schizophrenia revealed that inhibition of miR-4763-3p function alleviated anxiety symptoms and improved memory. The dopamine transporters in the striatal regions were significantly reduced in schizophrenia model mice as compared with wild-type mice, suggesting that inhibition of miR-4763-3p can lessen the symptoms of schizophrenia. Our findings demonstrate that miR-4763-3p may target RASD2 mRNA and thus may serve as a potential biomarker and therapeutic target for schizophrenia, providing a theoretical foundation for further studies of the molecular basis of this disease.

No abstract

This study aimed to explore the effects of different feeding restriction levels on the growth performance, intestinal immunity, and skeletal muscle development of meat rabbits. Additionally, we studied whether complete compensatory growth could be obtained post 2 weeks of restricted feeding, in order to seek a scientific mode of feeding restriction. Each of three groups was exposed to 3 weeks of feeding restriction and 2 weeks of compensatory growth. The 15% feeding restriction showed a negligible effect on the final body-weight of the rabbits (p > 0.05), but significantly reduced the feed-to-weight ratio (p < 0.05); reduced diarrhea and mortality; and increased digestive enzyme activity and antioxidant capacity. However, a 30% feeding-restriction level substantially reduced the growth rate of the rabbits (p < 0.05), impaired skeletal muscle development, and showed no compensatory growth after 2 weeks of nutritional recovery. Additionally, immunoglobulin and antioxidant enzyme synthesis were impaired due to reduced nutritional levels, and levels of pro-inflammatory factors were increased during the compensation period. The IGF1 mRNA expression decreased significantly (p < 0.05), whereas MSTN and FOXO1 expression increased noticeably (p < 0.05). Moreover, protein levels of p-Akt and p-p70 decreased significantly in the 15% feeding restriction group. Overall, the 15% feeding limit unaffected the weight and skeletal muscle development of rabbits, whereas the 30% feeding limit affected the growth and development of skeletal muscle in growing rabbits. The PI3K/Akt signaling pathway is plausibly a mediator of this process.