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Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.
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Objective To explore the effect of sublingual immunotherapy (S-LIT) on the balance of Th17/Treg in children with mite allergic asthma. Methods All 124 cases with mite allergic asthma were randomly divided into two groups, the control group (62 cases) was treated with ladder type inhalation, and the treatment group (62 cases) was administered of dust mite drops on the basis of conventional treatment. The peripheral frequency of Th17 cell and Treg cell of all the subjects (before and after treatment) were detected by flow cytometry, the serum cytokine IL-10、IL-17 levels wer analyzed by ELISA. Results After 1 year treatment, the Th17 cells in treatment group (1.50 %±0.87 %) was significantly lower than that before treatment (3.39 % ± 1.58 %), and less than that of the control group after 1 year of treatment (2.42 %±1.32 %) (P <0.01);after 1 year treatment, the proportion of Treg cells in treatment group (4.05 %±1.36 %) was significantly higher than that before treatment (2.33 ± 0.81%), and more than that of the control group after 1 year of treatment (2.87 %± 0.87 %) (P <0.01). After 1 year treatment, the serum IL-10 levels in treatment group (64.76±27.79 pg/mL) was significantly higher than that before treatment (36.32 ± 11.53 pg/mL), and more than that of the control group after 1 years of treatment (50.32 ± 10.97 pg/mL) (P <0.01);after 1 year treatment, the serum IL-17 levels in treatment group (20.45±8.35 pg/mL) was significantly lower than that before treatment (86.48 ± 28.19 pg/mL), and significantly less than that of the control group after 1 year of treatment (46.32 ± 12.43 pg/mL) (P <0.01). After 1 year treatment, the Childhood Asthma Control Test (C-ACT)score in the treatment group (24.35 ± 8.47) was significantly higher than the control group (20.13 ± 6.86) (P <0.05). Conclusions SLIT can decrease airway inflammation and correct the imbalance of Th17/Treg in children with mite, allergic asthma.
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OBJECTIVE@#To summarize the clinical features and early diagnostic evidence for mental disorders due to primary hypothyroidism after primary overactive thyroid surgery or 131I therapy. @*METHODS@#The retrospective analysis was conducted on 15 patients in terms of the clinical features with primary hypothyroidism-induced mental disorder after primary overactive thyroid surgery or 131I therapy. The data regarding past history of hyperthyroidism parallel operation or 131I treatment, thyroid function biochemical indexes were collected. @*RESULTS@#The free triiodothyronine (FT3) and free thyroxine (FT4) were decreased, while thyroid-stimulating hormone (TSH) was increased. The clinical symptoms included lazy, fatigue, and mood swings accompanied by mental retardation, behavioral disorders, hallucinations and delusions. Particularly, the severe patients were of disturbance of consciousness. @*CONCLUSION@#The clinical features of primary hypothyroidism-induced mental disorder are diverse and variable. It is not difficult to diagnose the mental disorder if the attention is paid on the medical history inquiry and thyroid function tests. However, it is easy to be misdiagnosed and missed diagnosis.
Subject(s)
Humans , Hypothyroidism , Mental Disorders , Retrospective Studies , Thyroid Function Tests , Thyrotropin , Thyroxine , TriiodothyronineABSTRACT
Ebola virus (EBOV) and Marburg virus (MARV) are causative agents of severe hemorrhagic fever with high mortality rates in humans and non-human primates and there is currently no licensed vaccine or therapeutics.To date,there is no specific laboratory diagnostic test in China,while there is a national need to provide differential diagnosis during outbreaks and for instituting acceptable quarantine procedures.In this study,the TaqMan RT-PCR assays targeting the nucleoprotein genes of the Zaire Ebolavirus (ZEBOV) and MARV were developed and their sensitivities and specificities were investigated.Our results indicated that the assays were able to make reliable diagnosis over a wide range of virus copies from 103 to 109,corresponding to the threshold of a standard RNA transcript.The results showed that there were about 1010 RNA copies per milliliter of virus culture supernatant,equivalent to 10,000 RNA molecules per infectious virion,suggesting the presence of many non-infectious particles.These data indicated that the TaqMan RT-PCR assays developed in this study will be suitable for future surveillance and specific diagnosis of ZEBOV and MARV in China.
ABSTRACT
Ebola virus(EBOV)and Marburg virus(MARV),belonging to the Filoviridae family,emerged four decades ago and caused severe viral hemorrhagic fever in human and other primates.As high as 50-90% mortality,filoviruses can cause significant threats to public health.However,so far no specific and efficient vaccine has been available,nor have other treatment methods proved to be effective.It is of great importance to detect these pathogens specific,rapidly and sensitively in order to control future filovirus outbreaks.Here,recent progresses in the development of detection and diagnosis methods for EBOV and MARV are summarized.
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Objective To explore the changes and clinical significance of serum cystatin-C, β2- mieroglobulin (β2-MG) and renal hemodynamic in children with Henoch-Schoenlein purpura(HSP). Method Forty-six patients with HSP are in HSP group, 40 healthy children are in control group. Serum cystatin-C was determined by enzyme-linked immunosorbent assay, β2-MG was detected by radioimmunoassay, renal hemodynamie was detected by colour Doppler ultrasound. Results Serum cystafin-C and β2-MG in HSP group [(3.96±1.52 ), (2.74±0.82)mg/L] were higher than those in control group [(1.67±0.61), (1.89±0.47)mg/L] (P<0.01). Frequenee spectra showed high velocity and resistance, and maximum crest flow rate[(1.068±0.348) m/s] and resistance index (0.894±0.125) in systolic phase of main renal arteries were obviously higher in HSP group than those in control group [(0.859±0.357) m/s and 0.726±0.078] (P<0.05). Conclusions The level of serum cystatin-C and the change of renal hemedynamie can act as the significant indicators of early diagnosis of HSP nephritis.