Air ; Humans ; Workplace

BackgroundSmad4,a key intracellular mediator in transforming growth factor-β (TGF-β)signaling,plays a critical role in the normal development of many tissues/organs.However,its functional role in the development of lacrimal gland has rarely been reported.ObjectiveThe aim of this study was to investigate the role that Smad4 may play in the development of lacrimal glands using Smad4 conditional knockout (CKO) mice( C57BL/6 mouse line),MethodsSmad4 in lacrimal glands,as well as in the lens,cornea and ectoderm of the eyelids,was conditionally inactivated by the Pax6 promoter-driven Cre transgenic mice and Smad4 conditional gene mice,LacZ reporter was used to visualize the developing lacrimal gland by X-gal staining,and standard histological approaches were used to reveal morphological changes.Six or more mice or embryos in each group were used for comparisons at the same stage.ResultsLacZ staining showed that E15.0,Smad4 CKO mice could still develop primary lacrimal bud,but much shorter than the wild-type ones.At E16.5,the primary lacrimal bud in wild-type mice began branching,but no branching was found in Smad4 CKO mice except that the primary lacimal bud became blunt at the tip.At E18.0,although Smad4 CKO mice develop some acini,the branching and size and number of acini were obviously less than ones in Smad4 wild-type mice.Based on histological findings,lacrimal glands in Smad4 CKO mice developed slowly,and the size was considerably smaller,and the numbers of lobes as well as the numbers of acini were much fewer than those of Smad4 wild-type mice lacrimal glands at various stages.Pigment and adipose tissue were also observed within the lacrimal glands starting from P7 in Smad4 CKO mice and increased with age growing.Lacrimal glands in mutant adult mice were eventually replaced by adipose tissue and accumulation of pigments.Conclusions These results support the notion that Smad4 is essential for the normal development and maintenance of the mouse LG and may be involved in the metabolism of pigment and adipose tissue in LG.

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.

Animals ; Cattle ; Chickens ; Dogs ; Sheep ; Swine ; Yersinia enterocolitica ; classification ; isolation & purification

Objective To evaluate the immunogenicity and immunoprotective effect of heat shock protein 60 kDa (SjHSP60) of Schistosoma japonicum in mice after immunization and challenge infection, and explore the mechanism. Methods B cell/an?tibody?related databases and analysis tools were used to predict B?cell epitopes of SjHSP60. The mice were immunized with the recombinant SjHSP60 and challenged with S. japonicum cercariae. SjHSP60?specific antibodies in serum were detected by ELI?SA. The level of splenocyte proliferation was determined by 3H?TdR incorporation. Ex vivo suppression assay was performed to in?vestigate the effects of CD4 +CD25 + regulatory T cells (Tregs) induced by SjHSP60. Results SjHSP60 possessed multiple pre?dominant regions of B?cell epitopes. SjHSP60 induced a significant increase in both SjHSP60?specific IgG levels (P < 0.01) and splenocyte proliferation (P < 0.01) with a higher IFN?γ production (P < 0.01). However, the immunization with SjHSP60 resulted no significant reduction in adult worms (P > 0.05) and liver?accumulated eggs (P > 0.05) in S. japonicum?infected mice. Ex vivo assay showed that CD4+CD25+ Tregs from SjHSP60?immunized mice enhanced immunosuppressive activity. Conclusion SjH?SP60 has a dual role in host immune system, being involved in the induction of dominant humoral and cellular immune responses as well as in the enhancement of immunosuppression.

Objective To evaluate the effect of nebulized bronchodilator on the change of tidal breathing in infants with asthma.This may provide some objective evidence for clinical diagnosis.Methods One hundred and five infants with asthma and 26 cases with pneumonia were involved for the study.Tidal breathing flow-volume was obtained before and 10-15 minutes after nebulized bronchodilator was given.Accor-ding to the basic lung function results,59 cases as a mild group [the ratio of time taken to reach peak expiratory flow to total expiratory time(TPTEF/Te) ≥15%],and 46 cases of the infant asthma as a severe group(TPTEF/Te0.05).Moreover,in severe group,expect for RR and expiratory time(Te),the other indices significantly increased after administration of nebulized bronchodilator(P

To establish a MacELISA method for the detection of IgM antibodies against Chikungunya virus (CHIKV), we prepared virus like particle (VLP) antigens of CHIKV using the whole structural protein C-E3-E2-6K-E1 encoding gene with a baculovirus expression system in Sf9 insect cells. The VLPs were purified and used to immunize Kunming mice. Then, polyclonal antibodies were purified from the samples of ascites with a protein G HiTrap SP column and labeled with horseradish peroxidase. A MacELISA method for the detection of IgM antibodies against CHIKV was assembled with goat anti-human IgM antibody, VLP antigens and an enzyme-labeled polyclonal antibody. The results were evaluated with a serum panel containing serum samples from laboratory-confirmed CHIK, HFRS patients, healthy donors, and commercially available CHIKV IgM as a quality control. It was shown that the MacELISA had a specificity of 99% (99/100), the coefficients of variation (CoV) within a plate were <10%, and the CoV of different ELISA plates in terms of the plate variation coefficient was <15%. A comparative analysis was performed to compare the current method against a commercial CHIKV IgM antibody detection kit for IIFA-IgM. The detection limit of MacELISA was significantly lower than that of the IIFA-IgM commercial kit (P< 0.0001). Here, we demonstrate that the VLP-based MacELISA is a promising tool for the early diagnosis and epidemiological investigation of CHIKV infection, with a high level of sensitivity and specificity for the detection of IgM antibodies against CHIKV.
Animals ; Antibodies, Viral ; blood ; Chikungunya Fever ; blood ; diagnosis ; virology ; Chikungunya virus ; immunology ; isolation & purification ; Enzyme-Linked Immunosorbent Assay ; methods ; Humans ; Immunoglobulin M ; blood ; Mice

BACKGROUNDCommon variable immunodeficiency (CVID) is one of the most common symptomatic primary immunodeficiency syndromes. The purpose of this article was to broaden our knowledge about CVID for better diagnosis and treatment.

METHODSClinical and immunological features of 40 Chinese patients with CVID were analyzed retrospectively.

RESULTSThe median age at onset was 11-year-old (range 4-51 years). The median age at diagnosis was 14.5-year-old (range 5-66 years). The average time of delay in diagnosis was 5.3 years (range 1-41 years). The most common main complaint was fever due to infections (35 cases, 87.5%). Pneumonia (28 cases, 70%) was the most common type of infections. Bronchiectasis was present in 6 patients (15%). Autoimmune disease was detected in 6 cases of CVID, and malignancy in 2 cases. The median total serum levels of IgG, IgA, and IgM at diagnosis were 1.07 g/L, 0.07 g/L, and 0.28 g/L, respectively. The percentages of CD3- /CD19 + B-cells were 1%-3.14%.

CONCLUSIONSInfection is the most frequent presentation of CVID. Patients with unexplainable infections should receive further examination including serum immunoglobulin (Ig) and lymphocyte subset analysis. Regular and sufficient substitution with Ig is recommended.

Adolescent ; Adult ; Aged ; Bronchiectasis ; drug therapy ; immunology ; pathology ; Child ; Child, Preschool ; China ; Common Variable Immunodeficiency ; drug therapy ; immunology ; pathology ; Humans ; Immunoglobulins ; metabolism ; Immunoglobulins, Intravenous ; Middle Aged ; Young Adult

To explore the mechanism of iron metabolism and its regulation as well as the roles of IRP(2) in ion metabolism of HL-60 cells, HL-60 cells were cultured in RPMI 1640 medium supplemented with 10% heat-inactivated fetal bovine serum, which was treated with ferric chloride (FeCl(3)) or deferoxamine (DFO). The cells were harvested at 12, 24 and 48 hours of proliferation, and total RNA was isolated; cDNA was synthesized by reverse transcription (RT), and relative expression levels of IRP(2) mRNA, Fn mRNA and TfR mRNA were determined by RT-PCR. The results showed at follows: (1) the level of IRP(2) mRNA remained constant in all cells, whether or not treated with DFO or FeCl(3). However, the expression of IRP(2) mRNA decreased when the time of cell culture was prolonged. There was no significant difference between groups (F(B-S) = 1.199, P > 0.05), but there was significant difference among the different time culture (F(W-S) = 43.418, P < 0.01). (2) Cells which treated neither with DFO nor ferri chloride showed significant difference from the control (F(W-S) = 7.184, F(B-S) = 113.926; P < 0.01). The level of TfR mRNA increased in the cells treated with DFO. Surprisingly, when cells treated with FeCl(3), there was not decline of TfR mRNA expression, but it increased lightly at 12 hours and peaked at 24 hours and declined drastically at 48 hours. (3) The level of Fn mRNA in the cells treated with FeCl(3) was approximately 2-fold as the control cells. In contrast with the control cells, there was significant difference (P < 0.05). The level of Fn mRNA of the cells treated with DFO had little change. As compared with the control cells, no significant difference was seen (P > 0.05). (4) There was not any significant correlation between IRP(2) mRNA and TfR mRNA or Fn mRNA in HL-60 cells (r = -0.005; r = 0.074; P > 0.05). It is concluded that (1) IRP(2) may regulate the iron metabolism in HL-60 cells by altering amounts of the IRP(2) 3.7- or 6.4-kb mRNA at the transcriptional level, or by IRP(2) degradation at the post transcriptional level. (2) Both of Fn mRNA and TfR mRNA participated, more or less, in the iron metabolism in HL-60 cells.
Ferritins ; genetics ; Gene Expression Regulation, Neoplastic ; HL-60 Cells ; Humans ; Iron Regulatory Protein 2 ; genetics ; RNA, Messenger ; genetics ; metabolism ; Receptors, Transferrin ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

Axons ; chemistry ; Myelin Sheath ; chemistry ; Staining and Labeling ; methods