Objective The prevalence of drug-resistant Mycobacterium tuberculosis (Mtb) strains is exacerbating the global burden of tuberculosis (TB), highlighting the urgent need for new treatment strategies for TB. Methods The recombinant adenovirus vaccine expressing cyclic di-adenosine monophosphate (c-di-AMP) phosphodiesterase B (CnpB) (rAd-CnpB), was administered to normal mice via mucosal immunization, either alone or in combination with drug therapy, to treat Mtb respiratory infections in mice.Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of antibodies in serum and bronchoalveolar lavage fluid (BALF). Real-time quantitative PCR was performed to assess the transcription levels of cytokines interferon γ(IFN-γ) and interleukin 10(IL-10) in mouse lungs. Flow cytometry was used to determine the proportions of CD4⁺ and CD8⁺ T cell subsets in the lungs and spleens. ELISA was employed to measure the levels of cytokines IFN-γ, IL-2, IL-10, inflammatory factors IL-6, and tumor necrosis factor α (TNF-α) secreted by spleen cells following antigen stimulation. The bacteria loads in the lungs and spleens of Mtb-infected mice were enumerated by plate counting methods. Resluts Intranasal immunization with rAd-CnpB induced high titers of IgG in mouse serum and the production of IgG and IgA in BALF, along with alterations in T lymphocyte subsets in the lungs and spleens. Administration of rAd-CnpB, either alone or in combination with drugs, to Mtb-infected mice significantly increased serum IgG levels as well as IgA and IgG levels in BALF. rAd-CnpB immunization promoted the secretion of CnpB-specific cytokines and inflammatory factors by splenocytes in Mtb-infected mice. However, rAd-CnpB immunotherapy, either alone or combined with drugs, did not significantly affect the bacterial loads in the lungs and spleens of mice with Mtb respiratory infections. Conclusion Mucosal immunization with rAd-CnpB induced significant mucosal, humoral and cellular immune responses in mice, and significantly enhanced CnpB-specific cellular immune responses in Mtb-infected mice.
Animals ; Adenoviridae/immunology* ; Mycobacterium tuberculosis/genetics* ; Mice ; Female ; Phosphoric Diester Hydrolases/genetics* ; Tuberculosis Vaccines/administration & dosage* ; Tuberculosis/prevention & control* ; Mice, Inbred BALB C ; Cytokines ; Lung/microbiology* ; Immunization ; Bronchoalveolar Lavage Fluid/immunology* ; Immunity, Mucosal

Objective:To investigate immunotherapy effects and mechanism of BCG and recombinant BCG(rBCG)with c-di-AMP as adjuvant on melanoma in mice model.Methods:Melanoma mice model was established by B16F10 cell subcutaneous injec-tion in groin,and treated with 1×106 CFU of BCG and rBCG by adjacent injection of subcutaneous tumor for 3 times,respectively.Survival of melanotic mice,tumor growth and metastasis were observed.Tumor tissues of mice were isolated to prepare cell suspen-sion,and proportion of immune cells were detected by flow cytometry.Transcriptional levels of immune-related genes in tumor tissues were detected by qRT-PCR.Results:Both BCG and rBCG immunotherapy could significantly inhibit growth in melanoma mice and prolong survival time of mice.rBCG showed better inhibition on metastasis than BCG.Both strains significantly reduced proportion of M2-type macrophages and myeloid-derived suppressor cell associated with tumor growth and metastasis.Both two strains promoted infiltration of lymphocytes in tumor tissues,and rBCG significantly increased proportion of B cells in tumor.BCG immunotherapy upregulated transcription levels of metastasis-related cytokines,while rBCG therapy had no effects on transcriptions of these genes.Conclusion:Both BCG and rBCG have immunotherapeutic effects on melanotic mice,and rBCG with c-di-AMP as adjuvant shows better inhibition on tumor metastasis than BCG,which mechanism was related to regulation of immune response in tumor tissues.

Psoriasis is a chronic,inflammatory,recurrent,and systemic disease mediated by immune dysregulation,which is often accompanied by psychological issues such as depression and anxiety.Recent research on the gut microbiota and depression and anxiety has made significant progress,with studies demonstrating that the gut microbiota plays a crucial role in the pathogenesis of psoriasis.Dysbiosis of the gut microbiota may be an important comorbidity mechanism linking psoriasis with depression and anxiety.This article summarizes the changes in the abundance of gut microbiota in patients with psoriasis and those with depression and anxiety,as well as how the gut microbiota influences this comorbidity through neural pathways and immune-endocrine pathways.It aims to provide novel perspectives for the study of the comorbidity mechanisms and clinical treatment of psoriasis and depression and anxiety.In the future,targeting the gut microbiota may enable the development of personalized treatments.

Psoriasis is a chronic,inflammatory,recurrent,and systemic disease mediated by immune dysregulation,which is often accompanied by psychological issues such as depression and anxiety.Recent research on the gut microbiota and depression and anxiety has made significant progress,with studies demonstrating that the gut microbiota plays a crucial role in the pathogenesis of psoriasis.Dysbiosis of the gut microbiota may be an important comorbidity mechanism linking psoriasis with depression and anxiety.This article summarizes the changes in the abundance of gut microbiota in patients with psoriasis and those with depression and anxiety,as well as how the gut microbiota influences this comorbidity through neural pathways and immune-endocrine pathways.It aims to provide novel perspectives for the study of the comorbidity mechanisms and clinical treatment of psoriasis and depression and anxiety.In the future,targeting the gut microbiota may enable the development of personalized treatments.

Objective:To investigate immunotherapy effects and mechanism of BCG and recombinant BCG(rBCG)with c-di-AMP as adjuvant on melanoma in mice model.Methods:Melanoma mice model was established by B16F10 cell subcutaneous injec-tion in groin,and treated with 1×106 CFU of BCG and rBCG by adjacent injection of subcutaneous tumor for 3 times,respectively.Survival of melanotic mice,tumor growth and metastasis were observed.Tumor tissues of mice were isolated to prepare cell suspen-sion,and proportion of immune cells were detected by flow cytometry.Transcriptional levels of immune-related genes in tumor tissues were detected by qRT-PCR.Results:Both BCG and rBCG immunotherapy could significantly inhibit growth in melanoma mice and prolong survival time of mice.rBCG showed better inhibition on metastasis than BCG.Both strains significantly reduced proportion of M2-type macrophages and myeloid-derived suppressor cell associated with tumor growth and metastasis.Both two strains promoted infiltration of lymphocytes in tumor tissues,and rBCG significantly increased proportion of B cells in tumor.BCG immunotherapy upregulated transcription levels of metastasis-related cytokines,while rBCG therapy had no effects on transcriptions of these genes.Conclusion:Both BCG and rBCG have immunotherapeutic effects on melanotic mice,and rBCG with c-di-AMP as adjuvant shows better inhibition on tumor metastasis than BCG,which mechanism was related to regulation of immune response in tumor tissues.

To prepare a lipid nanoparticle (LNP)-based subunit vaccine of Mycobacterium tuberculosis (Mtb) antigen EsxV and study its immunological characteristics, the LNP containing EsxV and c-di-AMP (EsxV: C: L) was prepared by thin film dispersion method, and its encapsulation rate, LNP morphology, particle size, surface charge and polyphase dispersion index were measured. BALB/c mice were immunized with EsxV: C: L by nasal drops. The levels of serum and mucosal antibodies, transcription and secretion of cytokines in lung and spleen, and the proportion of T cell subsets were detected after immunization. EsxV: C: L LNPs were obtained with uniform size and they were spherical and negatively charged. Compared with EsxV: C immunization, EsxV: C: L mucosal inoculation induced increased sIgA level in respiratory tract mucosa. Levels of IL-2 secreted from spleen and ratios of memory T cells and tissue-resident T cells in mice were also elevated. In conclusion, EsxV: C: L could induce stronger mucosal immunity and memory T cell immune responses, which may provide better protection against Mtb infection.
Animals ; Mice ; Mycobacterium tuberculosis ; Antigens, Bacterial ; Immunization ; Nanoparticles ; Vaccines, Subunit ; Mice, Inbred BALB C

Objective To investigate the effects of simulated 7 500 high altitude on the changes of such related indicators as heart rate variability (HRV),heart rate (HR),respiratory rate,body surface temperatures (BST),arterial oxygen saturation (SaO2) and blood pressure (BP) of the aviators flying 3 different types of aircraft.Methods Forty-nine aviators were chosen as research subjects,and were divided into 3 groups in accordance with the different types of aircraft they flew.Changes in HRV and other vital signs were observed in the aviators flying 3 different types of aircraft.Results As compared with that before hypoxia exposure,HR and BST of the aviators flying different types of aircraft were significantly increased,3 minutes after exposure to hypoxia (P ＜ 0.01),while SaO2 was significantly decreased (all P ＜ 0.01),and respiratory frequency was also decreased (P ＞ 0.05).Before exposure,the values of low frequency (LF),high frequency (HF) and total power (TP) of the aviators flying bombers were all obviously higher than those after exposure (P ＜ 0.05).The LF value before hypoxia was significantly higher than that of the aviators flying transports (P ＜ 0.05).Both before and after hypoxia,body surface temperature of the aviators flying fighters [(32.05 ± 1.16) 、(32.69 ±0.87)℃] was all significantly higher than that of the aviators flying bombers [(30.45 ± 2.13)、(31.76 ± 1.05) ℃] (P ＜ 0.05).Following exposure to hypoxia,the maximum A and minimum mean HRB difference of the aviators flying fighters was significantly higher than that before hypoxia exposure (P ＜ 0.01).Following exposure to hypoxia,the maximum mean respiratory rate of the aviators flying fighters was obviously decreased (P ＜ 0.05),and the maximum and minimum mean respiratory rate difference of the aviators was significantly lower than that before hypoxia exposure (P ＜ 0.05).Conclusions Following hypoxia for 3 minutes at a simulated altitude of 7 500 meters,HR and BST of the aviators in the 3 groups were all increased,SaO2 and respiratory rate were decreased,but BP was not significantly increased.There were variable differences in vital signs and HRV for the aviators flying different types of aircraft.

Objective To investigate the effects of simulated 7 500 high altitude on the changes of such related indicators as heart rate variability (HRV),heart rate (HR),respiratory rate,body surface temperatures (BST),arterial oxygen saturation (SaO2) and blood pressure (BP) of the aviators flying 3 different types of aircraft.Methods Forty-nine aviators were chosen as research subjects,and were divided into 3 groups in accordance with the different types of aircraft they flew.Changes in HRV and other vital signs were observed in the aviators flying 3 different types of aircraft.Results As compared with that before hypoxia exposure,HR and BST of the aviators flying different types of aircraft were significantly increased,3 minutes after exposure to hypoxia (P ＜ 0.01),while SaO2 was significantly decreased (all P ＜ 0.01),and respiratory frequency was also decreased (P ＞ 0.05).Before exposure,the values of low frequency (LF),high frequency (HF) and total power (TP) of the aviators flying bombers were all obviously higher than those after exposure (P ＜ 0.05).The LF value before hypoxia was significantly higher than that of the aviators flying transports (P ＜ 0.05).Both before and after hypoxia,body surface temperature of the aviators flying fighters [(32.05 ± 1.16) 、(32.69 ±0.87)℃] was all significantly higher than that of the aviators flying bombers [(30.45 ± 2.13)、(31.76 ± 1.05) ℃] (P ＜ 0.05).Following exposure to hypoxia,the maximum A and minimum mean HRB difference of the aviators flying fighters was significantly higher than that before hypoxia exposure (P ＜ 0.01).Following exposure to hypoxia,the maximum mean respiratory rate of the aviators flying fighters was obviously decreased (P ＜ 0.05),and the maximum and minimum mean respiratory rate difference of the aviators was significantly lower than that before hypoxia exposure (P ＜ 0.05).Conclusions Following hypoxia for 3 minutes at a simulated altitude of 7 500 meters,HR and BST of the aviators in the 3 groups were all increased,SaO2 and respiratory rate were decreased,but BP was not significantly increased.There were variable differences in vital signs and HRV for the aviators flying different types of aircraft.