Transferrin receptor is another receptor for SARS-CoV-2 entry

Angiotensin-converting enzyme 2 (ACE2) has been suggested as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry to cause coronavirus disease 2019 (COVID-19). However, no ACE2 inhibitors have shown definite beneficiaries for COVID-19 patients, applying the presence of another receptor for SARS-CoV-2 entry. Here we show that ACE2 knockout dose not completely block virus entry, while TfR directly interacts with virus Spike protein to mediate virus entry and SARS-CoV-2 can infect mice with over-expressed humanized transferrin receptor (TfR) and without humanized ACE2. TfR-virus co-localization is found both on the membranes and in the cytoplasma, suggesting SARS-CoV-2 transporting by TfR, the iron-transporting receptor shuttling between cell membranes and cytoplasma. Interfering TfR-Spike interaction blocks virus entry to exert significant anti-viral effects. Anti-TfR antibody (EC50 ~16.6 nM) shows promising anti-viral effects in mouse model. Collectively, this report indicates that TfR is another receptor for SARS-CoV-2 entry and a promising anti-COVID-19 target.

Serum from liver injury rats induces differentiation of umbilical cord mesenchymal stem cells into hepatocyte-like cells / 中国组织工程研究

BACKGROUND:Umbilical cord mesenchymal stem cels are from the umbilical cord of newly born individuals and have no ethical issues, and therefore are promising candidates for seeded cels as a substitute for cel transplantation and regenerative medicine. OBJECTIVE:To investigate the effects of serum from liver injury rats on induced differentiation of human umbilical cord mesenchymal stem cels into hepatocyte-like cels and provide experimental evidence for use of human umbilical cord mesenchymal stem cels in the treatment of patients with end-stage liver disease in the clinic. METHODS: Rat models of acute liver injury were established by intraperitoneal injection of 10% carbon tetrachloride. Rats in the control group were intraperitonealy administered the same amount of soybean oil. Forty-eight hours after modeling, abdominal aorta blood was taken for serum preparation. Passage 3 human umbilical cord mesenchymal stem cels were cultured with 20% serum from liver injury rats and 20% fetal bovine serum. Morphology of human umbilical cord mesenchymal stem cels was observed before and after culture. Levels ofα-fetoprotein and albumin in the supernatant were detected. RESULTS AND CONCLUSION:Cels exhibited shuttle-shaped appearance and grew in whirlpool-like manner at 1 day after culture with serum from liver injury rats, exhibited short shuttle-shaped appearance at 2 days, were oval-shaped at 3 days, and were round and an extremely smal number of cels were floated at 4 days. At 4 days after culture with serum from liver injury rats, level of albumin in the cel supernatant was significantly increased than that before induction and that in the control group (P< 0.001), and there was no significant difference in level of α-fetoprotein in the cel supernatant. These results suggest that serum of liver injury rats can induce differentiation of umbilical cord mesenchymal stem cels into hepatocyte-like cels.

Astragalus membranaceus injection promotes hepatocytic differentiation of umbilical cord blood stem cell: Enhancement of cell transplantation for the treatment of liver failure / 中国组织工程研究

BACKGROUND: Studies of umbilical cord blood stem cells transplantation for liver function failure have demonstrated that Astragalus membranaceus preparation can stimulate hemopoietic stem/progenitor cell proliferation.OBJECTIVE: To explore the effect of Astragalus membranaceus injection on the differentiation of umbilical cord blood stem cell into hepatocyte in vitro and in vivo for the treatment of liver failure. METHODS: The third and fourth passage of human umbilical cord blood stem cells (HUCBSCs) were collected. In drug screening test, there were 4 groups: cells were separately cultured with 0, 40, 200, and 400 mg/L Astragalus membranaceus injection to screen the appropriate for cell growth. In cell differentiation test, there were 2 groups: HUCBSCs were respectively cultured with hepatocyte growth factor (HGF, 10 μg/L), and HGF (10 μg/L) plus 200 mg/L Astragalus membranaceus injection. D-aminogalactose was intraperitoneally injected to establish a model of acute liver failure. Surviving model rats (48 hours) were randomly divided into six groups: model control, Astragalus membranaceus injection, rat peripheral blood mononuclear cells, combination, combination+Cytoxan, and combination+dexamethasone groups. The alpha fetoprotein mRNA and albumin mRNA expression was determined by RT-PCR, and liver function indexes were observed. RESULTS AND CONCLUSION: Different mass concentration of Astragalus membranaceus injection displayed varied influence on HUCBSC proliferation: 200 mg/L was the best for HUCBSC proliferation. Compared with HUCBSC cultured with HGF alone, the number of albumen-positive cells in HUCBSCs cultured with 200 mg/L Astragalus membranaceus injection and HGF was greater (P < 0.05). Moreover, the expression of albumen mRNA in combination, combination+Cytoxan, and combination+dexamethasone groups was greater than rat peripheral blood mononuclear cells group, while alpha fetoprotein mRNA expression was only greater than rat peripheral blood mononuclear cells group in early stage. At 7 days of treatment, the values of alanine aminotransferase, aspartate amino transferase and total bilirubin were significantly greater in combination, combination+Cytoxan, and combination+dexamethasone groups compared with model control, Astragalus membranaceus alone and rat peripheral blood mononuclear cells groups (P < 0.05), but no differences were observed among model control, Astragalus membranaceus alone and rat peripheral blood mononuclear cells groups (P > 0.05). Results indicate that Astragalus membranaceus injection at 200 mg/L can promote the proliferation and differentiation of HUCBSCs into hepatocyte in vitro and in vivo, ameliorate liver function and improve treatment effect of HUCBSC transplantation for liver failure.

Umbilical cord blood and blood plasma infusion for treating hepatitis :Grouping control and 1-year follow-up / 中国组织工程研究

BACKGROUND:Umbilical cord blood transplantation can ameliorate hepatic and immunologic function,repair hepatic injury,and promote hepatic regeneration,however,the differentiation mechanism and biological characteristics remain poorly understood,and the long-term efficiency need to be explored.OBJECTIVE:To investigate the long-term therapeutic efficacy of infusing umbilical cord blood and blood plasma in treating chronic severe hepatitis B patients.METHODS:Totally 50 chronic severe hepatitis B patients received treatment at the Second Xiangya Hospital,Central South University from January 2003 to January 2004 were randomly divided into the treatment and control groups,with 25 cases in each group.All patient were accepted an ordinary synthetic treatment,and the differences between age,pathogenetic condition,medication had no significance.The umbilical cord blood was obtained from healthy full-term spontaneous delivery parturient,centrifugated,remained karyotes and cord plasma,and used within 24 hours.Patients in the treatment group were received umbilical cord blood infusion,200 mL once,1 2 times per week,totally,each patients infused 4-8 times(mean 5 times);those in the control group were infused with adult fresh blood plasma.The changes of hemogram and hepatic function were measured.RESULTS AND CONCLUSION:All the patients were followed-up for 1 year.The hemogram and hepatic function indexes were similar in the 2 groups before treatment(P ＞ 0.05).The hemogram index had no obviously difference at 1 year after treatment (P ＞ 0.05),but the alanine aminotransferase and total bilirubin levels were decreased in the treatment compared with the control group(P ＜ 0.05),but the albumin was significantly increased(P ＜ 0.05).Compared with before treatment,the platelet level had no significant changes at 1 year after treatment,but the alanine aminotransferase and total bilirubin levels were deeply decreased(P＜ 0.05),albumin was significantly increased(P ＜ 0.05);the platelet and albumin levels were dramatically decreased in the control group(P ＜ 0.05).It suggested that umbilical cord blood infusion can improve the hepatic function and hemogram;therefore,it can be served as supplementary therapeutic measure for severe hepatitis.

Clinical character and therapeutic effect of late-onset Wilson disease / 中南大学学报(医学版)

OBJECTIVE@#To investigate the clinical character and therapeutic effect of late-onset Wilson disease,and to provide some evidence for its diagnosis and treatment.@*METHODS@#Clinical character, changes of copper metabolism, and therapeutic effect of 8 patients with late-onset Wilson disease were analyzed. Ceruloplasmin level was measured by nephelometry, and the copper contents in the serum, urine, and liver were measured by flame atomic absorption spectroscopy. The initial treatment was sodium dimercaptosulphonate, followed by D-penicillamine and/or zinc.@*RESULTS@#Patients with late-onset Wilson disease accounted for 7.0% of all patients, Who presented liver disease symptoms such as loss of appetite or nausea at the early stage and were misdiagnosed easily. Their blood routine and aminotransferase levels were normal in most patients with late-onset Wilson disease, and all patients had Kayser-Fleisher rings. There was significant difference between the liver function and copper metabolite test. The average urinary copper content was 4 072 microg/24 h on the first day after administrating sodium dimercaptosulphonate, which was 18.1 times as much as that before the treatment, and 2.5 times as much as that of D-penicillamine. No obvious adverse reactions were observed. The prognosis was usually good.@*CONCLUSION@#Enough attention should be paid to late-onset Wilson disease which is not rare and easy to be misdiagnosed. Good response can be expected in patients treated with sodium dimercaptosulphonate in the initial stage.

Protective effect of recombination rat augmenter of liver regeneration on kidney in acute renal failure rats / 中华肾脏病杂志

Objective To investigate the protective effects of recombination rat augmenter of liver regeneration (rrALR) on tubular cell injury and renal dysfunction in rats with acute renal failure (ARF)induced by gentamicin. Methods One hundred fifty female Wistar rots were randomly divided into 5 groups: group A (control), group B (gentamincin 140 mg/kg+ saline 100 μg/kg), group C (gentarnincin 140 mg/kg +blank plasmid 100 μg/kg), group Dl (gentaminein 140 mg/kg+rrALR 80 μg/kg), group D2 (gentamincin 140 mg/kg +rrALR 160 μg/kg). Rats were sacrificed at day 4, 8, 12, 16 and 21 after gentamicin first injection. Blood urea nitrogen (BUN), serum creatinine (Scr) and urine N-aeetyl-β-D-glucosaminidase (UNAG) were measured. The histopathologic changes were observed by periodic aeid-Schiff (PAS) staining. Protein expression of ALR and PCNA in renal tissue was detected using immtmohistochemistry and Western blot. Results Compared with control rots, the levels of BUN, Scr and UNAG were significantly increased in ARF rats at day 4, 8, 12 and 16 (P<0.05), however, the renal dysfunction and the renal histopathologieal injury were significantly improved in ARF rats simultaneously administered with rrALR (group D) compared with ARF rats (group B and C). The protein level of ALR, the number of PCNA positive tubular ceils and the proliferation index (PI) in group D were significantly higher than those of group B and C (P<0.05). Conclusion rrALR can promote the regeneration of tubular cells in nephrotoxie ARF rats and ameliorate renal dysfunction.

Human umbilical cord blood nucleated cell therapy in patients with chronic severe viral hepatitis / 中国输血杂志

Objective To investigate the therapeutic effect of human umbilical cord blood nucleated cell therapy(HUCBNCT) in patients with chronic severe viral hepatitis,and the effect of HUCBNCT on ductular proliferation and hepatic oval cell proliferation.Methods A total of 90 patients with chronic severe viral hepatitis were divided into two groups randomly,and the two groups were treated with adult plasma transfusion(control group),and HUCBNCT(treatment group),respectively.The therapeutic effect in all patients was evaluated by determination of liver function.Some patients had liver biopsy and CK19,CD34,albumin and AFP of the biopsy tissues were detected.Results Liver necrosis in treatment group was milder than that of control group,and the positive rate of CK19 staining in treatment group was higher than that of control group.Co-expression of CK19 and albumin were observed in some atypical ductular proliferation cells,which were like the oval cells in shape and immunohistochemical characteristics.Conclusion HUCBNCT,which can promote liver ductular and oval cell proliferation,may have promising therapeutic effect on patients with chronic severe viral hepatitis.

A Comparative study of serum sFas in patients with hepatocellular cancer and chronic hepatitis / 中南大学学报(医学版)

Objective　To study the effects of sFas in hepatocellular cancer (HCC) and chronic hepatitis (CH). Methods　The serum sFas was detected in 18 patients with HCC, 12 patients with CH and 6 cases of normal control by ELISA. Results　The serum sFas in HCC was obviously increased and had significant difference with the patients of CH and normal control (P<0.01). The serum sFas had positive correlation with the serum TBIL(P<0.01), but negative correlation with the ALB, PTA and the ratio of ALT/AST(P<0.01).Conclusions　sFas may resist the occurrence of HCC apoptosis. In CH, sFas has correlation with the severity of CH. The role of sFas in viral hepatitis is uncertain.

Treatment of hepatitis C after kidney transplantation with combined interferon-? and Ribovirin / 第三军医大学学报

ObjectiveTo investigate the treatment and safety of interferon ? plus Ribovirin for chronic hepatitis C after kidney transplantation. MethodsFive patients with chronic hepatitis C after kidney transplantation were administered with interferon ? (50 ?g) subcutaneously once a week, plus Ribovirin (600 mg) orally once daily. The levels of HCV-RNA, ALT and serum creatinine in patients’ serum were monitored monthly. ResultsFour in 5 patients presented normal ALT and negative HCV-RNA in serum 12 weeks after treatment, and obtained sustained viral response 24 weeks after interferon ? plus Ribovirin therapy. During treatment, renal graft rejection did not occur. The most frequent side-effects were the decrease of leukocyte and hemoglobin, myalgia and fever, but did not influence the course of treatment. ConclusionCombination of interferon ? with Ribovirin can be a valid therapeutic option in renal transplant recipients with hepatitis C, and shows no influence on the renal function.