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1.
bioRxiv ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38826233

ABSTRACT

The menstrual cycle influences the risk of acquiring sexually transmitted infections (STIs), including Chlamydia trachomatis (C. trachomatis), although the underlying immune contributions are poorly defined. A mouse model simulating the immune-mediated process of menstruation could provide valuable insights into tissue-specific determinants of protection against chlamydial infection within the cervicovaginal and uterine mucosae comprising the female reproductive tract (FRT). Here, we used the pseudopregnancy approach in naïve C57Bl/6 mice and performed vaginal challenge with Chlamydia muridarum (C. muridarum) at decidualization, endometrial tissue remodeling, or uterine repair. This strategy identified that the time frame comprising uterine repair correlated with robust infection and greater bacterial burden as compared with mice on hormonal contraception, while challenges during endometrial remodeling were least likely to result in a productive infection. By comparing the infection site at early time points following chlamydial challenge, we found that a greater abundance of innate effector populations and proinflammatory signaling, including IFNγ correlated with protection. FRT immune profiling in uninfected mice over pseudopregnancy or in pig-tailed macaques over the menstrual cycle identified NK cell infiltration into the cervicovaginal tissues and lumen over the course of endometrial remodeling. Notably, NK cell depletion over this time frame reversed protection, with mice now productively infected with C. muridarum following challenge. This study shows that the pseudopregnancy murine menstruation model recapitulates immune changes in the FRT as a result of endometrial remodeling and identifies NK cell localization at the FRT as essential for immune protection against primary C. muridarum infection.

2.
Heliyon ; 10(5): e26721, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38434409

ABSTRACT

Surface subsidence pits formed by mining disturbance are highly susceptible to slope instability under rainfall erosion, inducing underground debris flow disasters. To prevent and control underground debris flow disasters in a subsidence area, a test model of subsidence pit slope was established in accordance with the principle of similar simulation, and the erosion-resistant performance of moraine-cured slopes with different soil-slurry ratios and the law of runoff and sand production were investigated through the simulation of artificial rainfall and a simulation test of grouting. Results show that the initial rainfall production time increases exponentially with increasing soil-slurry ratio, while sediment production intensity decreases linearly with increasing rainfall duration. The evolution of soil erosion can be divided into five stages: impact infiltration, water-filled softening, stripping cutting, migration crossing, and steady flow equilibrium. Compared with in situ moraine, moraine particles after grouting between the generation of large amounts of Si-O-Si and Si-OH hydration products become loose and porous soil medium is transformed into a dense cemented structure. The soil-slurry ratio is 5:1, the sand-fixing effect increases by 28.8 times, the resistance of permeability increases by 11.3 times, and the grouting curing effect is remarkable. This study can provide technical support for the prevention and control of geological disasters in subsidence pits.

3.
Biomark Med ; 18(2): 51-57, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38358344

ABSTRACT

Background: To explore the relationship between homocysteine (Hcy) and cardiac surgery-associated acute kidney injury (AKI). Methods: A total of 944 patients who underwent cardiac surgery were enrolled. The association between Hcy levels and the risk of cardiac surgery-associated AKI was evaluated. Results: A total of 135 patients were diagnosed with AKI and the prevalence of AKI was 14.30%. The AKI group had significantly higher levels of Hcy compared with the non-AKI group (16.90 vs 13.56 umol/l; p < 0.001). The incidence rates of AKI increased from 7.2% to 26.72% across increasing Hcy quartiles (p < 0.001). Compared with the first Hcy quartile group, the odds ratio of cardiac surgery-associated AKI was 4.43 (95% CI: 2.27-8.66) in the highest Hcy group. Conclusion: Elevated Hcy level is an independent risk factor for cardiac surgery-associated AKI.


Subject(s)
Acute Kidney Injury , Cardiac Surgical Procedures , Humans , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Acute Kidney Injury/diagnosis , Cardiac Surgical Procedures/adverse effects , Risk Factors , Incidence , Prevalence , Postoperative Complications/etiology , Retrospective Studies
4.
World J Gastroenterol ; 30(1): 79-90, 2024 Jan 07.
Article in English | MEDLINE | ID: mdl-38293327

ABSTRACT

BACKGROUND: Laparoscopic radical gastrectomy is widely used, and perioperative complications have become a highly concerned issue. AIM: To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery, guide perioperative treatment strategies for gastric cancer patients, and prevent serious complications. METHODS: In total, 998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model, and 398 patients were included in the validation group. The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected. Three machine learning methods, lasso regression, random forest, and artificial neural networks, were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy, and their prediction efficacy and accuracy were evaluated. RESULTS: The constructed complication model, particularly the random forest model, could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy. It exhibited stable performance in external validation and is worthy of further promotion in more centers. CONCLUSION: Using the risk factors identified in multicenter datasets, highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established. We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.


Subject(s)
Laparoscopy , Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Retrospective Studies , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Laparoscopy/adverse effects , Gastrectomy/adverse effects , Gastrectomy/methods , Treatment Outcome
5.
Mucosal Immunol ; 17(1): 41-53, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37866719

ABSTRACT

Despite their importance for immunity against sexually transmitted infections, the composition of female reproductive tract (FRT) memory T-cell populations in response to changes within the local tissue environment under the regulation of the menstrual cycle remains poorly defined. Here, we show that in humans and pig-tailed macaques, the cycle determines distinct clusters of differentiation 4 T-cell surveillance behaviors by subsets corresponding to migratory memory (TMM) and resident memory T cells. TMM displays tissue-itinerant trafficking characteristics, restricted distribution within the FRT microenvironment, and distinct effector responses to infection. Gene pathway analysis by RNA sequencing identified TMM-specific enrichment of genes involved in hormonal regulation and inflammatory responses. FRT T-cell subset fluctuations were discovered that synchronized to cycle-driven CCR5 signaling. Notably, oral administration of a CCR5 antagonist drug blocked TMM trafficking. Taken together, this study provides novel insights into the dynamic nature of FRT memory CD4 T cells and identifies the menstrual cycle as a key regulator of immune surveillance at the site of STI pathogen exposure.


Subject(s)
CD4-Positive T-Lymphocytes , Genitalia, Female , Menstrual Cycle , Receptors, CCR5 , Signal Transduction , Female , Humans , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , Genitalia, Female/immunology , Genitalia, Female/metabolism , Menstrual Cycle/immunology , Menstrual Cycle/physiology , Receptors, CCR5/genetics , Receptors, CCR5/metabolism , T-Lymphocyte Subsets/immunology , Macaca nemestrina/immunology , Immunologic Memory , Cellular Microenvironment/immunology , Cellular Microenvironment/physiology , CCR5 Receptor Antagonists/pharmacology
6.
Ying Yong Sheng Tai Xue Bao ; 34(6): 1541-1546, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37694416

ABSTRACT

The development of precise climate risk zoning for chilling injury of Morchella esculenta can provide scientific basis for agricultural cultivation planning, dynamic assessment of chilling injury, and disaster prevention strategies. Based on meteorological data from 17 counties (cities) that located below the altitude of 3000 m in the Western Sichuan Plateau from 2011 to 2020, we analyzed the critical meteorological conditions for M. esculenta disasters in typical years. With the average yearly cold accumulation and cold injury frequency during the first day when the temperature remained stable between 5 ℃ and 10 ℃ during mushroom emergence as zoning indicators, we established a geographical spatial distribution model of the cold injury index, and then divided the risk level of M. esculenta cold injury in the Western Sichuan Plateau, evaluated the risk of cold injury. The results showed that the temperature index for chilling injury risk of M. esculenta in the study area was the daily minimum temperature ≤2.0 ℃. The daily average temperature <6.0 ℃ would cause slow growth or the cessation of growth, which was set as a warning indicator for chilling injury risk. Along the Dadu River and Minjiang River basins, the frequency of chilling injury on M. esculenta increased from south to north. Wenchuan, Maoxian, and Lixian had the fewest overall chilling injuries during the study period, whereas Jiulong, Yajiang, and Batang had the most. The duration for cold injury was mainly 1-3 d, followed by 4-5 d, and rarely for >5 d. The frequency of chilling injury lasting for more than 5 d in Xiangcheng, Batang, Jiulong, Yajiang, and Xiaojin was more than that lasting for 4-5 d. The annual average days of chilling injury of was 3.0-27.4 d, the daily average minimum temperature was -0.84-1.36 ℃, the extreme lowest temperature was -5.8-0.1 ℃, and the average accumulated cold was 0.16-9.64 ℃·d during the period of chilling injury. With the increases of elevation and latitude, the average days of chilling injury and the average accumulated cold increased. The largest duration of chilling injury was 3-20 d, the maximum accumulated cold was 0.44-13.34 ℃·d. The risk of chilling injury to M. esculenta increased from south to north and from low elevation to high elevation. The suitable planting areas were distributed in strips and branches along the direction of mountains and rivers, mainly in the flat areas of low mountains and valleys below the altitude of 2200 m, including Kangding, Luding, Danba, Wenchuan, Lixian, Maoxian, Jiuzhaigou, and Songpan.


Subject(s)
Cold Injury , Cold Temperature , Humans , China , Risk Assessment
7.
Front Immunol ; 13: 902515, 2022.
Article in English | MEDLINE | ID: mdl-35874682

ABSTRACT

H9N2 and H3N2 are the two most important subtypes of low pathogenic avian influenza viruses (LPAIV) because of their ongoing threat to the global poultry industry and public health. Although commercially available inactivated H9N2 vaccines are widely used in the affected countries, endemic H9N2 avian influenza remains uncontrolled. In addition, there is no available avian H3N2 vaccine. Influenza virus-like particles (VLPs) are one of the most promising vaccine alternatives to traditional egg-based vaccines. In this study, to increase the immunogenic content of VLPs to reduce production costs, we developed chimeric bivalent VLPs (cbVLPs) co-displaying hemagglutinin (HA) and neuraminidase (NA) of H9N2 and H3N2 viruses with the Gag protein of bovine immunodeficiency virus (BIV) as the inner core using the Bac-to-Bac baculovirus expression system. The results showed that a single immunization of chickens with 40µg/0.3mL cbVLPs elicited an effective immune response and provided complete protection against H9N2 and H3N2 viruses. More importantly, cbVLPs with accompanying serological assays can successfully accomplish the strategy of differentiating infected animals from vaccinated animals (DIVA), making virus surveillance easier. Therefore, this cbVLP vaccine candidate would be a promising alternative to conventional vaccines, showing great potential for commercial development.


Subject(s)
Influenza A Virus, H9N2 Subtype , Influenza in Birds , Vaccines, Virus-Like Particle , Animals , Antibodies, Viral , Cattle , Chickens , Influenza A Virus, H3N2 Subtype , Vaccination/veterinary , Vaccines, Inactivated
9.
Gastroenterol Rep (Oxf) ; 9(6): 589-594, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34925856

ABSTRACT

BACKGROUND: Urinary catheterization (UC) is a conventional perioperative measure for major abdominal operation. Optimization of perioperative catheter management is an essential component of the enhanced recovery after surgery (ERAS) programme. We aimed to investigate the risk factors of urinary retention (UR) after open colonic resection within the ERAS protocol and to assess the feasibility of avoiding urinary drainage during the perioperative period. METHODS: A total of 110 colonic-cancer patients undergoing open elective colonic resection between July 2014 and May 2018 were enrolled in this study. All patients were treated within our ERAS protocol during the perioperative period. Data on patients' demographics, clinicopathologic characteristics, and perioperative outcomes were collected and analysed retrospectively. RESULTS: Sixty-eight patients (61.8%) underwent surgery without any perioperative UC. Thirty patients (27.3%) received indwelling UC during the surgical procedure. Twelve (10.9%) cases developed UR after surgery necessitating UC. Although patients with intraoperative UC had a lower incidence of post-operative UR [0% (0/30) vs 15% (12/80), P = 0.034], intraoperative UC was not testified as an independent protective factor in multivariate logistic analysis. The history of prostatic diseases and the body mass index were strongly associated with post-operative UR. Six patients were diagnosed with post-operative urinary-tract infection, among whom two had intraoperative UC and four were complicated with post-operative UR requiring UC. CONCLUSION: Avoidance of urinary drainage for open elective colonic resection is feasible with the implementation of the ERAS programme as the required precondition. Obesity and a history of prostatic diseases are significant predictors of post-operative UR.

10.
Int J Gen Med ; 14: 6035-6045, 2021.
Article in English | MEDLINE | ID: mdl-34588807

ABSTRACT

OBJECTIVE: Alternative polyadenylation (APA) is a common mechanism that is present in most human genes and determines the length of the messenger ribonucleic acid (mRNA) three prime untranslated region (3'-UTR), which can give rise to changes in mRNA stability and localization. However, little is known about the specific changes related to APA in stomach adenocarcinomas (STADs). METHODS: We integrated RNA sequencing data from The Cancer Genome Atlas and Genotype-Tissue Expression project to comprehensively analyze APA events in 289 cases of STAD. RESULTS: Our results showed that APA events were widespread in patients with STAD and were rich in genes related to known STAD pathways. The APA events result in the loss of tumor-suppressing micro-ribonucleic acid (miRNA) binding sites and increased heterogeneity in the length of the 3'-UTR altered genes. Survival analysis revealed that specific subsets of 3'-UTR-altered genes independently characterized a poor prognostic cohort among patients with STAD, thereby indicating the potential of APA as a new prognostic biomarker. CONCLUSION: Our single-cancer analysis showed that by losing miRNA regulation, APA can become a driving factor for regulating the expression of oncogenic genes in STAD and promote its development. Our research revealed that APA events regulated STAD genes that were functionally related, thereby providing a new approach for gaining a better understanding of the progress of STADs and a means for identifying new drug targets as avenues of treatment.

11.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(2): 334-339, 2021 Mar.
Article in Chinese | MEDLINE | ID: mdl-33829711

ABSTRACT

OBJECTIVE: To investigate the status of osteoporosis and cardiovascular calcification in patients with chronic kidney disease (CKD) with different stages, and analyze the correlation between the stages and markers of bone metabolism To correlation. METHODS: A total of 368 CKD patients at stage 3-5 who were treated in First Affiliated Hospital Affiliate to Chongqing Medical University and Chongqing Fuling Central Hospital from July 2017 to January 2018 were enrolled. A total of 60 healthy people who underwent physical examination in the hospital during the same period were enrolled as control group. Age, gender and body mass index (BMI) of all study objects at enrollment time were collected. The levels of estimate glomerular filtration rate (eGFR), serum calcium (Ca), phosphorus (P), albumin (ALB), intact parathyroid hormone (iPTH), bone alkaline phosphatase (BALP), procollagen Ⅰ N-terminal peptide (PINP) and ß-crosslaps (ß-CTX) were detected. The occurrence of osteoporosis, vascular calcification and heart valve calcification was detected. Pearson correlation analysis was applied to analyze correlation between eGFR, serum bone metabolism markers and osteoporosis, cardiovascular calcification. RESULTS: Compared with control group, levels of serum P, iPTH, BALP, PINP and ß-CTX were significantly increased in CKD stage 3-5 group ( P<0.05), while levels of eGFR and serum Ca were decreased ( P<0.05). With the increase of CKD staging, changes of their levels were more significant ( P<0.05). The incidence of vascular calcification and heart valve calcification in CKD stage 5 hemodialysis group was higher than that in CKD stage 3-4 group and CKD stage 5 without dialysis group ( P<0.05). eGFR was positively correlated with serum Ca in CKD patients at stage 3-5 ( P<0.05), while negatively correlated with serum P, iPTH, BALP, PINP and ß-CTX ( P<0.05). The occurrence of osteoporosis, vascular calcification and heart valve calcification was negatively correlated with increase of eGFR and serum Ca levels in CKD patients at stage 3-5 ( P<0.05), while positively correlated with increase of levels of serum P, iPTH, BALP, PINP and ß-CTX ( P<0.05). CONCLUSION: The levels of serum bone metabolism markers and eGFR are closely related to occurrence of osteoporosis and cardiovascular calcification in CKD patients at stage 3-5.


Subject(s)
Osteoporosis , Renal Insufficiency, Chronic , Biomarkers , Cross-Sectional Studies , Glomerular Filtration Rate , Humans , Osteoporosis/etiology , Parathyroid Hormone , Renal Insufficiency, Chronic/complications
12.
Sci Adv ; 6(35): eabb2119, 2020 08.
Article in English | MEDLINE | ID: mdl-32923636

ABSTRACT

Whether monocytes contribute to the brain microglial pool in development or after brain injury remains contentious. To address this issue, we generated CCR2-CreER mice to track monocyte derivatives in a tamoxifen-inducible manner. This method labeled Ly6Chi and Ly6Clo monocytes after tamoxifen dosing and detected a surge of perivascular macrophages before blood-brain barrier breakdown in adult stroke. When dosed by tamoxifen at embryonic day 17 (E17), this method captured fetal hematopoietic cells at E18, subdural Ki67+ ameboid cells at postnatal day 2 (P2), and perivascular microglia, leptomeningeal macrophages, and Iba1+Tmem119+P2RY12+ parenchymal microglia in selective brain regions at P24. Furthermore, this fate mapping strategy revealed an acute influx of monocytes after neonatal stroke, which gradually transformed into a ramified morphology and expressed microglial marker genes (Sall1, Tmem119, and P2RY12) for at least 62 days after injury. These results suggest an underappreciated level of monocyte-to-microglia transition in development and after neonatal stroke.


Subject(s)
Microglia , Stroke , Animals , Mice , Mice, Inbred C57BL , Microglia/metabolism , Monocytes/metabolism , Receptors, CCR2/genetics , Receptors, CCR2/metabolism , Stroke/genetics , Stroke/metabolism , Tamoxifen
14.
J Virol ; 94(20)2020 09 29.
Article in English | MEDLINE | ID: mdl-32759317

ABSTRACT

Recent studies on chronic viral infections have defined a novel programmed cell death 1-positive (PD-1+) T cell factor 1-positive (TCF1+) stem-like CD8 T cell subset that gives rise to the terminally differentiated exhausted CD8 T cells. In this study, we performed T cell receptor beta (TCRß) sequencing of virus-specific CD8 T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection to examine the TCR diversity and lineage relationship of these two functionally distinct subsets. We found that >95% of the TCR repertoire of the exhausted CD8 T cell subset was shared with the stem-like CD8 T cells. The TCR repertoires of both CD8 T cell subsets were composed mostly of a few dominant clonotypes, but there was slightly more breadth and diversity in the stem-like CD8 T cells than their exhausted counterpart (∼40 versus ∼15 GP33+ clonotypes; ∼20 versus ∼7 GP276+ clonotypes). Interestingly, the breadth of the TCR repertoire was broader during the early stages (day 8) of the chronic infection than the later stages (days 45 to 60), showing that there was a narrowing of the TCR repertoire during chronic infection (∼2-fold GP33+ and GP276+ stem-like subset; ∼10-fold GP33+ and ∼5-fold GP276+ exhausted subset). In contrast, during acute LCMV infection, the TCR repertoire was much broader in both GP33-specific effector (∼160 clonotypes) and memory CD8 T cells (∼160 clonotypes). Overall, our data demonstrate that the virus-specific CD8 T cell TCR repertoire is broad and remains stable after acute LCMV infection, but it contracts and is narrower during chronic infection. Our study also shows that the repertoire of the exhausted CD8 T cell subset is almost completely derived from the stem-like CD8 T cell subset during established chronic LCMV infection.IMPORTANCE CD8 TCR repertoires responding to chronic viral infections (HIV, hepatitis C virus [HCV], Epstein-Barr virus [EBV], and cytomegalovirus [CMV]) have limited breadth and diversity. How these repertoires change and are maintained throughout the chronic infection are unknown. We thus characterized the LCMV-specific CD8 TCR repertoires of stem-like and terminally exhausted subsets generated during chronic LCMV infections. During chronic LCMV infections, the repertoires started as diverse but became more clonal at the late time point. Further, the exhausted subset was composed of dominant clonotypes that were shared with the stem-like subset. Together, we demonstrate that the TCR repertoire contracts over time and is almost exclusively derived from the stem-like subset late during the persistent viral infection. Our data suggest that dominant clonotypes in the exhausted subset are derived from a diverse pool of stem-like clonotypes, which may be contributing to the clonality observed during chronic viral infections.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Lymphocytic Choriomeningitis/immunology , Lymphocytic choriomeningitis virus/immunology , Receptors, Antigen, T-Cell/immunology , Animals , Chronic Disease , Female , Lymphocytic Choriomeningitis/genetics , Lymphocytic choriomeningitis virus/genetics , Mice , Receptors, Antigen, T-Cell/genetics
15.
Mol Ther Nucleic Acids ; 19: 853-864, 2020 Mar 06.
Article in English | MEDLINE | ID: mdl-31982772

ABSTRACT

Gastric cancer (GC) is among the most frequently occurring malignancies worldwide. In recent years, long noncoding RNAs (lncRNAs) have been widely studied because of their ability to regulate the cellular processes involved with tumorigenesis. The present study aims to investigate the underlying molecular mechanism by which lncRNA urothelial carcinoma-associated 1 (UCA1) influences the progression of GC. Differentially expressed lncRNA UCA1 was initially identified by microarray-based analysis, after which a high expression of UCA1 was determined in GC tissues and cells. It is important to note that UCA1 could upregulate the expression of phosphatase of regenerating liver-3 (PRL-3) by sponging miR-495. The expression of UCA1 and miR-495 was altered in human GC cells to evaluate cell activity in vitro, as well as peritoneal metastasis and tumor formation ability in vivo. Results suggested that increased expression of UCA1 promoted cell proliferation, migration, and invasion, accompanied by suppressed cell apoptosis, as well as enhanced peritoneal metastasis and tumorigenesis of GC cells. Meanwhile, the upregulated expression of miR-495 could reverse the promotive effects exerted by UCA1. Taken conjointly, UCA1, as a competing endogenous RNA (ceRNA) of miR-495, could accelerate the development of GC by upregulating PRL-3, highlighting a potentially promising basis for the targeted intervention treatment of GC.

16.
Nat Immunol ; 21(3): 309-320, 2020 03.
Article in English | MEDLINE | ID: mdl-31953534

ABSTRACT

Tissue-resident memory T cells (TRM cells) are critical for cellular immunity to respiratory pathogens and reside in both the airways and the interstitium. In the present study, we found that the airway environment drove transcriptional and epigenetic changes that specifically regulated the cytolytic functions of airway TRM cells and promoted apoptosis due to amino acid starvation and activation of the integrated stress response. Comparison of airway TRM cells and splenic effector-memory T cells transferred into the airways indicated that the environment was necessary to activate these pathways, but did not induce TRM cell lineage reprogramming. Importantly, activation of the integrated stress response was reversed in airway TRM cells placed in a nutrient-rich environment. Our data defined the genetic programs of distinct lung TRM cell populations and show that local environmental cues altered airway TRM cells to limit cytolytic function and promote cell death, which ultimately leads to fewer TRM cells in the lung.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Cellular Reprogramming/genetics , Cellular Reprogramming/immunology , Epigenesis, Genetic/immunology , Immunologic Memory/genetics , Lung/immunology , Animals , Apoptosis/immunology , CD8-Positive T-Lymphocytes/cytology , Cell Survival/genetics , Cell Survival/immunology , Cellular Microenvironment/genetics , Cellular Microenvironment/immunology , Female , Lung/cytology , Male , Mice , Mice, Inbred C57BL , Orthomyxoviridae Infections/genetics , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/pathology
17.
Cancer Gene Ther ; 27(7-8): 548-557, 2020 08.
Article in English | MEDLINE | ID: mdl-31391530

ABSTRACT

NPS-2143 is a calcium-sensing receptor (CaSR) antagonist that has been demonstrated to possess anticancer activity. To date, the effects of NPS-2143 on gastric cancer (GC) cell growth, motility, and apoptosis have not been investigated. In the present study, we firstly investigated the expression of CaSR in GC tissues using immunohistochemistry and western blotting. Then Cell Counting Kit-8 and colony formation assays were conducted to explore the effect of the NPS-2143 on the proliferation of GC cell line AGS. Transwell invasion and migration assays were performed to test the effect of NPS-2143 on AGS cell motility. We determined the percentage of apoptotic cells by flow cytometry and explored the changes of apoptosis-related protein by western blotting. Furthermore, we constructed a CaSR knockdown AGS cell line to determine whether NPS-2143 acted via inhibition of CaSR. We found that the protein expression level of CaSR was higher in GC tissues compared with the paired adjacent normal tissues. In addition, NPS-2143 treatment caused an inhibitory effect on the proliferation, invasion, and migration of AGS cells and a promoting effect on AGS apoptosis. The expression of Bcl-2 was decreased while the levels of Bax and active caspase 3 were enhanced in AGS cells after NPS-2143 treatment. Mechanistically, NPS-2143 lead to a significant decrease in the expression of phosphorylated (p)-AKT, phosphorylated mechanistic target of rapamycin (p-mTOR), p70, and cyclin D1. Knockdown of CaSR also suppressed cell proliferation, invasion, and migration and promoted cell apoptosis. No significant difference was observed between CaSR-silenced AGS cells with and without NPS-2143 treatment. These results confirmed that NPS-2143 has an inhibitory influence on AGS cell growth via inhibiting CaSR, which then suppresses the PI3K/Akt signaling pathway.


Subject(s)
Cell Proliferation , Naphthalenes/therapeutic use , Receptors, Calcium-Sensing/antagonists & inhibitors , Signal Transduction , Stomach Neoplasms/drug therapy , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Apoptosis , Cell Line, Tumor , Cell Movement , Humans , Naphthalenes/pharmacology , Neoplasm Invasiveness , Receptors, Calcium-Sensing/metabolism , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Stomach Neoplasms/physiopathology
18.
Mucosal Immunol ; 13(1): 161-171, 2020 01.
Article in English | MEDLINE | ID: mdl-31723250

ABSTRACT

Lung resident memory CD8 T cells (TRM) are critical for protection against respiratory viruses, but the cellular interactions required for their development are poorly understood. Herein we describe the necessity of classical monocytes for the establishment of lung TRM following influenza infection. We find that, during the initial appearance of lung TRM, monocytes and dendritic cells are the most numerous influenza antigen-bearing APCs in the lung. Surprisingly, depletion of DCs after initial T cell priming did not impact lung TRM development or maintenance. In contrast, a monocyte deficient pulmonary environment in CCR2-/- mice results in significantly less lung TRM following influenza infection, despite no defect in the antiviral effector response or in the peripheral memory pool. Imaging shows direct interaction of antigen-specific T cells with antigen-bearing monocytes in the lung, and pulmonary classical monocytes from the lungs of influenza infected mice are sufficient to drive differentiation of T cells in vitro. These data describe a novel role for pulmonary monocytes in mediating lung TRM development through direct interaction with T cells in the lung.


Subject(s)
Influenza A Virus, H3N2 Subtype/physiology , Influenza, Human/immunology , Lung/immunology , Monocytes/immunology , Orthomyxoviridae Infections/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocytes/immunology , Aged , Animals , Cell Differentiation , Cell Movement/genetics , Cells, Cultured , Humans , Immunologic Memory , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptors, CCR2/genetics , Receptors, CCR2/metabolism
19.
JCI Insight ; 4(10)2019 05 16.
Article in English | MEDLINE | ID: mdl-31092736

ABSTRACT

We explored the association between violence victimization and increased risk for acquiring sexually transmitted infections (STIs) in women by measuring cellular immune barrier properties from the female reproductive tract. STI-negative participants reporting repeated prior victimization occurrences through the lifetime trauma and victimization history (LTVH) instrument were more likely to exhibit alterations in barrier homeostasis and the composition of critical immune mediators irrespective of demographic parameters or presence of bacterial vaginosis. By combining cellular data with mixed-effect linear modeling, we uncovered differences in local T cells, MHCII+ antigen-presenting cells, and epithelial cells indicative of altered trafficking behavior, increased immunosuppressive function, and decreased barrier integrity at sites of STI exposure that correlate most strongly with LTVH score. These data evidence a biological link between a history of violence victimization and risk of STI acquisition through immune dysregulation in the female reproductive tract.


Subject(s)
Crime Victims , Sexually Transmitted Diseases/immunology , Violence , Adolescent , Adult , Biomarkers , Cell Adhesion , Cell Movement , Female , HIV Infections , Humans , Longitudinal Studies , Middle Aged , T-Lymphocytes , Vaginosis, Bacterial/immunology , Young Adult
20.
J Med Internet Res ; 21(3): e12127, 2019 03 19.
Article in English | MEDLINE | ID: mdl-30888328

ABSTRACT

BACKGROUND: Problem-Based-Learning (PBL) has been widely accepted in student-centered medical education. Since WeChat is the most popular communication app in China, we have chosen to use WeChat as new platform for online PBL in order to reduce the limitations of traditional PBL in dental practical clerkships. OBJECTIVE: This study aims to demonstrate the feasibility and acceptability of online PBL using WeChat (WeChat-PBL) in a dental practical clerkship. METHODS: A total of 72 students in a dental practical clerkship and 10 tutors participated in this study from June to August 2017. We created 10 WeChat groups to provide a communication platform for the PBL teaching, in which the students selected the PBL cases themselves from their practical clerkship. After each individual PBL case, group members were required to complete an evaluation on the PBL process itself. A final questionnaire survey was completed by the participants to summarize the long-term evaluation of the whole WeChat-PBL experience after the 3-month clerkship. Data from the PBL cases, WeChat messages, periodic evaluations, and long-term evaluations were collected for analysis. RESULTS: There were 45 cases presented in the WeChat-PBL within the 3-month clerkship. All students had positive reactions to the communication within the PBL groups. The results of the periodic evaluation showed that the students and tutors were quite satisfied with the process of WeChat-PBL and appreciated the group members' contributions and performance. The final questionnaire results indicated that the WeChat-PBL had achieved positive effects. CONCLUSIONS: The results of this study indicate the feasibility and acceptability of the app, WeChat, for problem-based learning in a dental practical clerkship.


Subject(s)
Education, Dental/methods , Education, Distance/methods , Problem-Based Learning/methods , Feasibility Studies , Humans , Surveys and Questionnaires
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