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1.
Immunol Res ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39034374

RESUMO

BACKGROUND: The cause of food allergy (FA) is still a mystery. Telomerases are involved in the regulation of immune responses. This study aims to gain an understanding of the contribution of telomerase reverse transcriptase (TERT) to the pathogenesis of FA. METHODS: A murine FA model was established with ovalbumin as the specific antigen. The role of TERT in regulating dendritic cell (DC) immune tolerogenic functions was evaluated in this murine model. RESULTS: We observed that the Tert promoter was at demethylation status and the Tert expression was elevated in DCs of FA mice. The Tert expression in DCs had a positive correlation with the FA response. TERT prevented the induction of Il10 expression in DCs. The immune tolerogenic functions of DCs were diminished by TERT. The immune tolerogenic functions of DC were restored by CpG by boosting the Tert promoter methylation. Administration of CpG promoted the therapeutic effects of allergen specific immunotherapy in FA mice. CONCLUSIONS: Low levels of Il10 expression and high levels of Tert expression were observed in intestinal DCs of FA mice. CpG exposure restored the expression of Il10 and increased the therapeutic benefits of allergen-specific immunotherapy.

2.
Exploration (Beijing) ; 4(3): 20230086, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38939869

RESUMO

The ongoing mutations of the SARS-CoV-2 pose serious challenges to the efficacy of the available antiviral drugs, and new drugs with fantastic efficacy are always deserved investigation. Here, a nanobody called IBT-CoV144 is reported, which exhibits broad neutralizing activity against SARS-CoV-2 by inducing the conformation of spike trimer dimers. IBT-CoV144 was isolated from an immunized alpaca using the RBD of wild-type SARS-CoV-2, and it showed strong cross-reactive binding and neutralizing potency against diverse SARS-CoV-2 variants, including Omicron subvariants. Moreover, the prophylactically and therapeutically intranasal administration of IBT-CoV144 confers fantastic protective efficacy against the challenge of Omicron BA.1 variant in BALB/c mice model. The structure analysis of the complex between spike (S) protein, conducted using Cryo-EM, revealed a special conformation known as the trimer dimers. This conformation is formed by two trimers, with six RBDs in the "up" state and bound by six VHHs. IBT-CoV144 binds to the lateral region of the RBD on the S protein, facilitating the aggregation of S proteins. This aggregation results in steric hindrance, which disrupts the recognition of the virus by ACE2 on host cells. The discovery of IBT-CoV144 will provide valuable insights for the development of advanced therapeutics and the design of next-generation vaccines.

3.
Cell Signal ; 121: 111257, 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38857681

RESUMO

Epithelial barrier dysfunction plays an important role in the pathogenesis of Th2 bias. The mechanism requires further clarification. NEMO is associated with regulating apoptotic activities in the cell. The purpose of this study is to investigate the role of insufficient Nemo signals in developing Th2 bias in the respiratory tract. Nemof/fEpcam-Cre mice (A mouse strain carrying NEMO-deficient epithelial cells. NemoKO mice, in short) was generated. An airway Th2 bias mouse model was established with the ovalbumin/alum protocol. The NemoKO mice exhibited spontaneous airway Th2 bias. Respiratory tract epithelial barrier integrity was compromised in NemoKO mice. Apoptosis was found in approximately 10% of the epithelial cells of the respiratory tract in NemoKO mice. The reconstruction of the Nemo expression restored homeostasis within the epithelial barrier of the airways. Restoration of Nemo gene expression in epithelial cells by Nemo mRNA vaccination alleviated Th2 bias in mice with airway allergy. To sum up, NEMO plays an important role in maintaining the integrity of the epithelial barrier in the respiratory tract. Administration of NEMO mRNA vaccines can restore epithelial barrier functions and alleviate Th2 bias in the airways.

4.
Imeta ; 3(1): e165, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38868519

RESUMO

Consumption of dietary fiber and anthocyanin has been linked to a lower incidence of colorectal cancer (CRC). This study scrutinizes the potential antitumorigenic attributes of a black rice diet (BRD), abundantly rich in dietary fiber and anthocyanin. Our results demonstrate notable antitumorigenic effects in mice on BRD, indicated by a reduction in both the size and number of intestinal tumors and a consequent extension in life span, compared to control diet-fed counterparts. Furthermore, fecal transplants from BRD-fed mice to germ-free mice led to a decrease in colonic cell proliferation, coupled with maintained integrity of the intestinal barrier. The BRD was associated with significant shifts in gut microbiota composition, specifically an augmentation in probiotic strains Bacteroides uniformis and Lactobacillus. Noteworthy changes in gut metabolites were also documented, including the upregulation of indole-3-lactic acid and indole. These metabolites have been identified to stimulate the intestinal aryl hydrocarbon receptor pathway, inhibiting CRC cell proliferation and colorectal tumorigenesis. In summary, these findings propose that a BRD may modulate the progression of intestinal tumors by fostering protective gut microbiota and metabolite profiles. The study accentuates the potential health advantages of whole-grain foods, emphasizing the potential utility of black rice in promoting health.

5.
Phys Chem Chem Phys ; 26(24): 17383-17395, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38860766

RESUMO

Although GaN is a promising candidate for semiconductor devices, degradation of GaN-based device performance may occur when the device is bombarded by high-energy charged particles during its application in aerospace, astronomy, and nuclear-related areas. It is thus of great significance to explore the influence of irradiation on the microstructure and electronic properties of GaN and to reveal the internal relationship between the damage mechanisms and physical characteristics. Using a combined density functional theory (DFT) and ab initio molecular dynamics (AIMD) study, we explored the low-energy recoil events in GaN and the effects of point defects on GaN. The threshold displacement energies (Eds) significantly depend on the recoil directions and the primary knock-on atoms. Moreover, the Ed values for nitrogen atoms are smaller than those for gallium atoms, indicating that the displacement of nitrogen dominates under electron irradiation and the created defects are mainly nitrogen vacancies and interstitials. The formation energy of nitrogen vacancies and interstitials is smaller than that for gallium vacancies and interstitials, which is consistent with the AIMD results. Although the created defects improve the elastic compliance of GaN, these radiation damage states deteriorate its ability to resist external compression. Meanwhile, these point defects lead the Debye temperature to decrease and thus increase the thermal expansion coefficients of GaN. As for the electronic properties of defective GaN, the point defects have various effects, i.e., VN (N vacancy), Gaint (Ga interstitial), Nint (N interstitial), and GaN (Ga occupying the N lattice site) defects induce the metallicity, and NGa (N occupying the Ga lattice site) defects decrease the band gap. The presented results provide underlying mechanisms for defect generation in GaN, and advance the fundamental understanding of the radiation resistances of semiconductor materials.

7.
Immunol Res ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829493

RESUMO

Monkeypox cases continue to increase globally, and there is an urgent need to develop a highly effective vaccine against monkeypox. This study investigated the binding and authentic-virus neutralizing activities of sera from mice immunized with EEV (extracellularly enveloped viruses) antigens B6R and A35R, and IMV (intrinsic material viruses) antigens M1R, A29L, E8L, and H3L against monkeypox virus. The results showed that immunizations of A35R and E8L could only induce lower titers of binding antibodies, in contrast, immunization of M1R induced the highest titers of binding antibodies, while immunization of B6R, H3L, and A29L induced moderate titers of binding antibodies. For the live monkeypox virus neutralization assay, the results showed that immunization with two doses of EEV antigen B6R did not effectively induce humoral immune responses to neutralize monkeypox live virus, immunization with EEV-A35R only induced weak monkeypox-neutralizing antibodies. In contrast, the immunization of the four types of monkeypox virus IMV antigens can all induce neutralizing antibodies against authentic monkeypox virus, among them, A29L and H3L induced the highest neutralizing antibody titers. The results of this study provide important references for the selection of antigens in the development of the next generation of monkeypox vaccines.

8.
Cell Immunol ; 401-402: 104829, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38754338

RESUMO

Eosinophils account for a significant portion of immune cells in the body. It is well known that eosinophils play a role in the pathogenesis of many diseases. In which the interaction between eosinophils and other immune cells is incompletely understood. The aim of this study is to characterize the immune suppressive functions of eosinophils. In this study, an irway allergy mouse model was established. Eosinophils were isolated from the airway tissues using flow cytometry cell sorting. The RAW264.7 cell line was used to test the immune suppressive functions of eosinophils. We observed that eosinophils had immune suppressive functions manifesting inhibiting immune cell proliferation and cytokine release from other immune cells. The eosinophil's immune suppressive functions were mediated by eosinophil-derived molecules, such as eosinophil peroxidase (EPX) and major basic protein (MBP). The expression of Ras-like protein in the brain 27a (Rab27a) was detected in eosinophils, which controlled the release of MBP and EPX by eosinophils. Eosinophil mediators had two contrast effects on inducing inflammatory responses or rendering immune suppressive effects, depending on the released amounts. Administration of an inhibitor of Rab27a at proper dosage could alleviate experimental airway allergy. To sum up, eosinophils have immune suppressive functions and are also inflammation inducers. Rab27a governs the release of EPX and MBP from eosinophils, which leads to immune suppression or inflammation. Modulation of Rab27a can alleviate airway allergy responses by modulating eosinophil's immune suppressive functions, which has the translational potential for the management of eosinophil-related diseases.


Assuntos
Peroxidase de Eosinófilo , Eosinófilos , Animais , Eosinófilos/imunologia , Eosinófilos/metabolismo , Camundongos , Células RAW 264.7 , Peroxidase de Eosinófilo/metabolismo , Camundongos Endogâmicos BALB C , Citocinas/metabolismo , Citocinas/imunologia , Modelos Animais de Doenças , Proteína Básica Maior de Eosinófilos/metabolismo , Proteína Básica Maior de Eosinófilos/imunologia , Feminino , Hipersensibilidade/imunologia , Proliferação de Células , Inflamação/imunologia
9.
Nat Commun ; 15(1): 4488, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802350

RESUMO

Understanding of infection dynamics is important for public health measures against monkeypox virus (MPXV) infection. Herein, samples from multiple body sites and environmental fomites of 77 acute MPXV infections (HIV co-infection: N = 42) were collected every two to three days and used for detection of MPXV DNA, surface protein specific antibodies and neutralizing titers. Skin lesions show 100% positivity rate of MPXV DNA, followed by rectum (88.16%), saliva (83.78%) and oropharynx (78.95%). Positivity rate of oropharynx decreases rapidly after 7 days post symptom onset (d.p.o), while the rectum and saliva maintain a positivity rate similar to skin lesions. Viral dynamics are similar among skin lesions, saliva and oropharynx, with a peak at about 6 d.p.o. In contrast, viral levels in the rectum peak at the beginning of symptom onset and decrease rapidly thereafter. 52.66% of environmental fomite swabs are positive for MPXV DNA, with highest positivity rate (69.89%) from air-conditioning air outlets. High seropositivity against A29L (100%) and H3L (94.74%) are detected, while a correlation between IgG endpoint titers and neutralizing titers is only found for A29L. Most indexes are similar between HIV and Non-HIV participants, while HIV and rectitis are associated with higher viral loads in rectum.


Assuntos
Anticorpos Antivirais , Monkeypox virus , Mpox , Eliminação de Partículas Virais , Humanos , Masculino , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Estudos Prospectivos , Adulto , Monkeypox virus/imunologia , Mpox/imunologia , Mpox/virologia , Mpox/epidemiologia , Saliva/virologia , Saliva/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Pessoa de Meia-Idade , Estudos Longitudinais , DNA Viral , Orofaringe/virologia , Orofaringe/imunologia , Coinfecção/imunologia , Coinfecção/virologia , Coinfecção/epidemiologia , Carga Viral , Fômites/virologia
10.
Immunol Lett ; 267: 106867, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38754636

RESUMO

Chronic inflammation is the pathological feature of inflammatory bowel diseases (IBD), but its etiology is unknown. Macrophages are one of the major immune cell fractions in the colon. The objectives of this study are to characterize the immune regulatory functions of macrophages in the colon of patients with ulcerative colitis (UC). UC patients (n = 30) were recruited into this study. Colon lavage fluid (CLF) was collected. Macrophages are isolated from the cellular components of CLF. The immune suppressive functions of macrophages were assessed using immunological approaches. We observed that macrophages occupied about half of the proportions of the cellular components in CLF. Lower amounts of IL10 mRNA and proteins were detected in macrophages of the UC group than the normal control (NC) group. The expression of IL10 in CLF macrophages was positively correlated with the UC-associated cytokines, including tumor necrosis factor-α, interleukin (IL)-1ß, IFN-γ, eosinophil-derived mediators, in CLF. The immune suppressive functions of CLF macrophages in UC patients were impaired. The inducibility of IL10 expression of UC M0 cells was defective as compared with NC M0 cells. Exposure to CpG restored the inducibility of IL10 expression in UC M0 cells, and gain the potential to acquire the immune suppressive functions. To sum up, the immune suppressive functions of UC macrophages are impaired. The inducibility of IL10 expression of M0 cells is impaired, which can be restored by the treatment with CpG.


Assuntos
Colite Ulcerativa , Citocinas , Interleucina-10 , Macrófagos , Humanos , Colite Ulcerativa/imunologia , Colite Ulcerativa/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Feminino , Masculino , Adulto , Interleucina-10/metabolismo , Pessoa de Meia-Idade , Citocinas/metabolismo , Células Cultivadas , Colo/imunologia , Colo/patologia , Colo/metabolismo
11.
Org Lett ; 26(8): 1550-1555, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38364868

RESUMO

We report a three-component Nozaki-Hiyama-Kishi type reaction of 1,3-dioxolane, 1,3-butadienes, and aldehydes to access masked aldehyde-incorporated homoallylic alcohols, facilitated by photo-hydrogen atom transfer (HAT)/chromium dual catalysis. The diaryl ketone serves dual roles both in the HAT process and in facilitating the turnover of the chromium catalyst. A range of functional groups are tolerated owing to the mild conditions. Both aromatic and aliphatic aldehydes are suitable substrates for coupling with several 1,3-butadienes and 1,3-dioxolane.

12.
Protein Cell ; 15(2): 121-134, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37470320

RESUMO

Continual evolution of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus has allowed for its gradual evasion of neutralizing antibodies (nAbs) produced in response to natural infection or vaccination. The rapid nature of these changes has incited a need for the development of superior broad nAbs (bnAbs) and/or the rational design of an antibody cocktail that can protect against the mutated virus strain. Here, we report two angiotensin-converting enzyme 2 competing nAbs-8H12 and 3E2-with synergistic neutralization but evaded by some Omicron subvariants. Cryo-electron microscopy reveals the two nAbs synergistic neutralizing virus through a rigorous pairing permitted by rearrangement of the 472-489 loop in the receptor-binding domain to avoid steric clashing. Bispecific antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutralization against recent variants including currently dominant XBB.1.5. Together, these findings expand our understanding of the potential strategies for the neutralization of SARS-CoV-2 variants toward the design of broad-acting antibody therapeutics and vaccines.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Microscopia Crioeletrônica , Anticorpos Neutralizantes , Anticorpos Antivirais
13.
Biosci Trends ; 17(6): 503-507, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38072446

RESUMO

The main technological difficulties of developing an intracellular (transmembrane) transport system for protein drugs lie in two points: i) overcoming the barriers in the cellular membrane, and ii) loading enough protein drugs, and particularly high-dose proteins, into particles. To address these two technological problems, we recently developed a novel cholesterol tag (C-Tag)-based transmembrane transport system. This pilot study found that the C-Tag dramatically improved the cellular uptake of Fab (902-fold, vs. Fab alone) into living cells, indicating that it successfully achieved transmembrane transport. Moreover, C-Tag-mediated membrane transport was verified using micron-scale large unilamellar vesicles (LUVs, approximately 1.5 µm)-based particles. The C-Tagged Fab was able to permeate the liposomal bilayer and it greatly enhanced (a 10.1-fold increase vs. Fab alone) internalization of proteins into the LUV-based particles, indicating that the C-Tag loaded enough proteins into particles for use of high-dose proteins. Accordingly, we established a novel C-Tag-based transport system that has overcome the known technological difficulties of protein transmembrane delivery, and this might be a useful technology for drug development in the future.


Assuntos
Colesterol , Lipossomos , Projetos Piloto , Transporte Biológico , Colesterol/metabolismo
14.
Int Immunopharmacol ; 126: 111336, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38056196

RESUMO

OBJECTIVES: Degranulation of mast cells leads to direct allergic symptoms. The underlying mechanism needs to be explored further. Endoplasmic reticulum (ER) stress is involved in the pathogenesis of allergic conditions. The objective of this study is to gain a better understanding of the mechanism of mast cell degranulation. METHODS: Bone marrow derived mast cells and mast cells isolated from the airway tissues were prepared. The role of ER stress in mediating the release of mast cells was tested. RNA sequencing (RNAseq) was used to investigate the genetic activities of mast cells. RESULTS: Our observation showed that sensitization increased ER stress in mast cells. X-box-1 binding protein (XBP1) activity was linked to mast cell degranulation. Modulation of ER stress or XBP1 expression regulates the release of the mast cell mediator. XBP1 promoted the mediator release of mast cells by activating spleen tyrosine kinase (Syk). Activation of eukaryotic initiation factor 2a (eIF2a) inhibited XBP1 in mast cells. Semaphorin 3A was effective in preventing experimental allergic rhinitis (AR) due to its ability to suppress the release of mast cell mediators. CONCLUSIONS: ER stress is associated with the mast cell degranulation. By inhibiting XBP1, the crucial molecule of ER stress, mast cell degranulation can be suppressed and experimental AR can be mitigated.


Assuntos
Degranulação Celular , Mastócitos , Estresse do Retículo Endoplasmático
15.
Immunol Res ; 72(2): 320-330, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37999823

RESUMO

Food allergy (FA) is a common immune disorder that involves dysfunctional immune regulation. More remedies for restoring immune regulation are necessary. Semaphorin 3 A (Sema3a) is a secreted protein of the semaphorin family, which plays a role in immune responses at all stages. The objective of this study is to gain an understanding of how Sema3a can restore the immune regulatory abilities of type 1 regulatory T cells (Tr1 cells). In this study, blood samples were taken from patients with FA. Tr1 cells were purified from blood samples using flow cytometry cell sorting, using LAG3 and CD49b as surface markers. RNA sequencing was employed to examine the characteristics of Tr1 cells. We observed an exaggerated increase in ER stress in peripheral Tr1 cells of FA patients. Enforced expression of spliced X-box protein-1 (XBP1s, one of the key molecules in ER stress) resulted in suppression of interleukin (IL)-10 expression in CD4+ T cells. Eukaryotic initiation factor 2a (eIF2a) mediated the effects of XBP1 on suppressing IL-10 expression in Tr1 cells. The use of Sema3a resulted in a decrease in ER stress, and an increase in IL-10 expression in Tr1 cells of FA patients. Sema3a administration reduced experimental FA by increasing the number of Tr1 cells. In conclusion, IL-10 expression in Tr1 cells is disturbed by ER stress. Sema3a treatment restores the expression of IL-10 and the immunosuppressive capability of Tr1 cells.

16.
Org Lett ; 26(1): 264-268, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38147643

RESUMO

A highly efficient photoinduced iron-catalyzed method has been developed for the direct use of alcohols as surrogates for organometallic reagents in the synthesis of tertiary alcohols. This method can be applied to both primary and secondary alcohols with diverse structures, enabling their reaction with aryl ketones under mild conditions. A variety of functional groups, including those that are typically reactive under conventional tertiary alcohol synthesis conditions, are compatible. Mechanistically, this reaction proceeds through the direct addition of the radical to the carbonyl pathway.

17.
Entropy (Basel) ; 25(10)2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37895573

RESUMO

Due to the early formation of rolling bearing fault characteristics in an environment with strong background noise, the single use of the time-varying filtering empirical mode decomposition (TVFEMD) method is not effective for the extraction of fault characteristics. To solve this problem, a new method for early fault detection of rolling bearings is proposed, which combines multipoint optimal minimum entropy deconvolution adjusted (MOMEDA) with parameter optimization and TVFEMD. Firstly, a new weighted envelope spectrum kurtosis index is constructed using the correlation coefficient and envelope spectrum kurtosis, which is used to identify the effective component and noise component of the bearing fault signal decomposed by TVFEMD, and the intrinsic mode function (IMF) containing rich fault information is selected for reconstruction. Then, a new synthetic impact index (SII) is constructed by combining the maximum value of the autocorrelation function and the kurtosis of the envelope spectrum. The SII index is used as the fitness function of the gray wolf optimization algorithm to optimize the fault period, T, and the filter length, L, of MOMDEA. The signal reconstructed by TVF-EMD undergoes adaptive filtering using the MOMEDA method after parameter optimization. Finally, an envelope spectrum analysis is performed on the signal filtered by the adaptive MOMEDA method to extract fault feature information. The experimental results of the simulated and measured signals indicate that this method can effectively extract early fault features of rolling bearings and has good reliability. Compared to the classical FSK, MCKD, and TVFEMD-MOMEDA methods, the first-order correlated kurtosis (FCK) and fault feature coefficient (FFC) of the filtered signal obtained using the proposed method are the largest, while the sample entropy (SE) and envelope spectrum entropy (ESE) are the smallest.

18.
Infect Drug Resist ; 16: 6269-6276, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37750173

RESUMO

Purpose: The purpose was to review relevant clinical data and formulate recommendations supporting the use of saline as a simple rinse for an early reassuring intervention to reduce the occurrence of re-positive COVID-19 patients. Methods: We conducted a single-centre retrospective cohort study, which enrolled patients with confirmed re-testing positive COVID-19 during 7-60 days after discharge from Third People's Hospital of Shenzhen. By one-to-two propensity score matching for age and sex, the control group of those not re-testing positive during the same period served as matched control. Results: A total of 223 patients were included in our study, 94 in re-positive group and 129 in non-re-positive group. The result shows that the rates of nasal douche treatment in the non-re-positive group were considerably higher than that of the re-positive group. And the Ct value of nasal douche group increased faster than that of non-nasal douche group after the Ct value reaching ≥35. Further analysis revealed that the higher the Ct value at the time of readmission, the shorter the time of average Ct values to reach ≥35. Conclusion: These findings suggest that nasal douche is beneficial to shorten the time of virus nucleic acid turning negative, thereby reducing the incidence of re-positive. The prevention and control of epidemics focuses on re-positive patients with Ct values <35.

19.
Adv Sci (Weinh) ; 10(25): e2206238, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37400423

RESUMO

Men demonstrate higher incidence and mortality rates of colorectal cancer (CRC) than women. This study aims to explain the potential causes of such sexual dimorphism in CRC from the perspective of sex-biased gut microbiota and metabolites. The results show that sexual dimorphism in colorectal tumorigenesis is observed in both ApcMin/ + mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice with male mice have significantly larger and more tumors, accompanied by more impaired gut barrier function. Moreover, pseudo-germ mice receiving fecal samples from male mice or patients show more severe intestinal barrier damage and higher level of inflammation. A significant change in gut microbiota composition is found with increased pathogenic bacteria Akkermansia muciniphila and deplets probiotic Parabacteroides goldsteinii in both male mice and pseudo-germ mice receiving fecal sample from male mice. Sex-biased gut metabolites in pseudo-germ mice receiving fecal sample from CRC patients or CRC mice contribute to sex dimorphism in CRC tumorigenesis through glycerophospholipids metabolism pathway. Sexual dimorphism in tumorigenesis of CRC mouse models. In conclusion, the sex-biased gut microbiome and metabolites contribute to sexual dimorphism in CRC. Modulating sex-biased gut microbiota and metabolites could be a potential sex-targeting therapeutic strategy of CRC.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Masculino , Feminino , Animais , Camundongos , Neoplasias Colorretais/patologia , Sulfato de Dextrana , Carcinogênese , Transformação Celular Neoplásica
20.
iScience ; 26(4): 106498, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37091242

RESUMO

This study aims to characterize the impaired immune regulatory function of Mφ obtained from UC patient colon lavage fluid (CLF). Mφs were the largest proportion (21.3 4.0%) of the CLF-derived cellular components. Less abundant and weaker immune suppressive function were observed in M2 Mφs (M2 cells) of the ulcerative colitis (UC) group. High levels of endoplasmic reticulum (ER) stress associated molecules were detected in UC M2 cells. The spliced X box binding protein-1 (XBP1) gene was negatively correlated with programmed death ligand-1 (PD-L1) in UC M2 cells. XBP1 promoted the expression of ring-finger protein 20 (Rnf20) in M2 cells. Rnf20 reduced PD-L1 abundance in UC M2 cells and impaired the immune suppressive ability. Inhibition of Rnf20 restored the immune regulating capacity of M2 cells and suppressed experimental colitis.

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