ABSTRACT
The ongoing and devastating pandemic of coronavirus disease 2019 (COVID-19) has led to a global public health crisis. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can potentially pose a serious risk to maternal and neonatal health. Cases of abnormal pregnancy and vertical transmission of SARS-CoV-2 from mother to foetus have been reported but no firm conclusions are drawn. Trophoblasts are the major constituents of the placenta to protect and nourish the developing foetus. However, direct in vivo investigation of trophoblasts susceptibility to SARS-CoV-2 and of COVID-19 and pregnancy is challenging. Here we report that human early syncytiotrophoblasts (eSTBs) are highly susceptible to SARS-CoV-2 infection in an angiotensin-converting enzyme 2 (ACE2)-dependent manner. From human expanded potential stem cells (hEPSCs), we derived bona fide trophoblast stem cells (TSCs) that resembled those originated from the blastocyst and the placenta in generating functional syncytiotrophoblasts (STBs) and extravillus trophoblasts (EVTs) and in low expression of HLA-A/B and amniotic epithelial (AME) cell signature. The EPSC-TSCs and their derivative trophoblasts including trophoblast organoids could be infected by SARS-CoV-2. Remarkably, eSTBs expressed high levels of ACE2 and produced substantially higher amounts of virion than Vero E6 cells which are widely used in SARS-CoV-2 research and vaccine production. These findings provide experimental evidence for the clinical observations that opportunistic SARS-CoV-2 infection during pregnancy can occur. At low concentrations, two well characterized antivirals, remdesivir and GC376, effectively eliminated infection of eSTBs by SARS-CoV-2 and middle east respiratory syndrome-related coronavirus (MERS-CoV), and rescued their developmental arrest caused by the virus infection. Several human cell lines have been used in coronavirus research. However, they suffer from genetic and/or innate immune defects and have some of the long-standing technical challenges such as cell transfection and genetic manipulation. In contrast, hEPSCs are normal human stem cells that are robust in culture, genetically stable and permit efficient gene-editing. They can produce and supply large amounts of physiologically relevant normal and genome-edited human cells such as eSTBs for isolation, propagation and production of coronaviruses for basic research, antivirus drug tests and safety evaluation.
ABSTRACT
This study was aimed to observe the protective effect of extract from Rhizoma A nemones Raddeanae (RAR) on hepatic fibrosis induced by porcine serum in rats. A total of 68 SD rats were randomly divided into 5 groups, which were the normal group, model group, RAR group, extraction of RAR (EXRAR) group, Fu-Zheng Hua-Y u(FZHY) group. Each rat was intraperitoneally injected with 0.5~0.6 ml of porcine serum twice a week for 15 suc-cessive weeks to establish liver fibrosis model. Intragastric administration was given after the model was successfully established. The FZHY group was given FZHY capsule (0.525 g·kg-1). The RAR group was given RAR decoction (0.7 g·kg-1). The EXRAR group was given EXRAR (0.071 g·kg-1). The model group and normal group were given e-qual amount of physiological saline. The medication was given once a day. And the treatment course was 8 weeks. At the end of the 23th week, rats were sacrificed. Contents of SOD and MDA in blood serum were assayed. The protein expressions of α-SMA and TGF-β1 in liver tissues were detected by SABC. The results showed that compared with the model group, content of MDA decreased in the EXRAR group, RAR group and FZHY group (P<0.05), and content of SOD increased obviously (P<0.05). In the model group, expression of α-SMA and TGF-β1 increased, with dark brown dyeing and diffusion area. Expression area and strength of the FZHY group, RAR group, and EXRAR group were ob-viously weak with tasteless interval dyeing and no formation of typical pseudolobule in comparison with the model group. The color rendering index showed that compared with the model group, the protein expression of α-SMA and TGF-β1 decreased obviously in liver tissues of the FZHY group, EXRAR group, and RAR group (P< 0.05). It was concluded that RAR and its extract had a good antifibrosis effect. And the EXRAR had basically the same antifibrosis effect as RAR. It was assumed that the possible mechanism was related with the inhibiting of hepatic stellate cell (HSC) activation and the expression of TGF-β1 as well as the resisting of lipid peroxidation.
ABSTRACT
AIM: To observe the effect of small dose ephedrine on hypote ns ion as the lithotomy position in laying down legs after the aged in the operatio ns with epidural anesthesia. METHODS: Twenty-seven ASA Ⅰ-Ⅱma le patients, aged 65-83 (71? 6.5 ) years undergoing transurethral resection of prostate (TURP) with the lithotomy position were randomly assigned to two gro ups by double blind method: ephedrine group (n=13) and contrasti ve group (n=14). The continual epidural anesthesia was administe red in T 12 -L 1 and L 3-4 for all patients used 1.5 % lidocaine. W hen the operation was finished off, before thirty seconds of horizontal position laying down legs, 15 mg ephedrine was iv at ephedrine group and 3 ml saline wat er at control group. After legs were laid down on the lithotomy position, variab les of SBP, MBP and P were recorded in ten minutes. RESULTS: Dur ing ten minutes after double legs were laid down, the variables were lightly ris en about 8.7 % to 76.9 % in ephedrine group and were fallen about 7.8 % to 85.7 % in control group. The difference on variables of two groups was significant (P
