Single-cell transcriptomics reveals CD8+ T cell structure and developmental trajectories in idiopathic pulmonary fibrosis.

Immune cells in the human lung are associated with idiopathic pulmonary fibrosis. However, the contribution of different immune cell subpopulations to the pathogenesis of pulmonary fibrosis remains unclear. We used single-cell RNA sequencing data to investigate the transcriptional profiles of immune cells in the lungs of 5 IPF patients and 3 subjects with non-fibrotic lungs. In an identifiable population of immune cells, we found increased percentage of CD8+ T cells in the T cell subpopulation in IPF. Monocle analyzed the dynamic immune status and cell transformation of CD8+ T cells, as well as the cytotoxicity and exhausted status of CD8+ T cell subpopulations at different stages. Among CD8+ T cells, we found differences in metabolic pathways in IPF and Ctrl, including lipid, amino acid and carbohydrate metabolic. By analyzing the metabolites of CD8+ T cells, we found that different populations of CD8+ T cells in IPF have unique metabolic characteristics, but they also have multiple identical up-regulated or down-regulated metabolites. In IPF, signaling pathways associated with fibrosis were enriched in CD8+ T cells, suggesting that CD8+ T cells may have an important contribution to fibrosis. Finally, we analyzed the interactions between CD8+ T cells and other cells. Together, these studies highlight key features of CD8+ T cells in the pathogenesis of IPF and help to develop effective therapeutic targets.

Comparing the impact of personal trainer guidance to exercising with others: Determining the optimal approach.

This study aimed to examine the effects of supervised fitness training under the guidance of a personal trainer and those of competitive fitness training with others and reveal the effects of specific differences between them in a detailed manner. The study's participants consisted of 66 healthy male adults (age: 29.2 ± 5.4 years). The participants were divided into three groups: the individual training group (n = 21), which served as the control group; the exercising with a partner group (n = 22); and the group trained by a personal trainer (n = 23). Each participant was subsequently assessed using one repetition maximum bench press, squats, skeletal muscle mass, fat mass, and a questionnaire regarding nutritional plan and injury to compare the effects of training sessions over a period of 12 weeks. Among the three groups, only the group trained by a personal trainer showed an obvious enhancement in fat reduction compared to baseline (-1.61 kg, p = 0.033), which was suggestive of a salient trend that far surpassed those of the individual training group and the exercising with a partner group. Regarding squats, only the group trained by a personal trainer showed a significant change compared to the individual training group (p = 0.003). Regarding the participants' consistent use of a nutritional plan, only the group trained by a personal trainer exhibited a palpable tendency (p < 0.001); furthermore, the effect of preventing injury in the group trained by a personal trainer was more notable than that in the individual training group and the exercising with a partner group. Our results indicate that a fitness personal trainer service is effective in expediting the process of achieving fitness goals in a relatively safe manner, thereby substantiating the diversified values of the fitness personal trainer service.

Proteomic analyses of smear-positive/negative tuberculosis patients uncover differential antigen-presenting cell activation and lipid metabolism.

Background: Tuberculosis (TB) remains a major global health concern, ranking as the second most lethal infectious disease following COVID-19. Smear-Negative Pulmonary Tuberculosis (SNPT) and Smear-Positive Pulmonary Tuberculosis (SPPT) are two common types of pulmonary tuberculosis characterized by distinct bacterial loads. To date, the precise molecular mechanisms underlying the differences between SNPT and SPPT patients remain unclear. In this study, we aimed to utilize proteomics analysis for identifying specific protein signatures in the plasma of SPPT and SNPT patients and further elucidate the molecular mechanisms contributing to different disease pathogenesis. Methods: Plasma samples from 27 SPPT, 37 SNPT patients and 36 controls were collected and subjected to TMT-labeled quantitative proteomic analyses and targeted GC-MS-based lipidomic analysis. Ingenuity Pathway Analysis (IPA) was then performed to uncover enriched pathways and functionals of differentially expressed proteins. Results: Proteomic analysis uncovered differential protein expression profiles among the SPPT, SNPT, and Ctrl groups, demonstrating dysfunctional immune response and metabolism in both SPPT and SNPT patients. Both groups exhibited activated innate immune responses and inhibited fatty acid metabolism, but SPPT patients displayed stronger innate immune activation and lipid metabolic inhibition compared to SNPT patients. Notably, our analysis uncovered activated antigen-presenting cells (APCs) in SNPT patients but inhibited APCs in SPPT patients, suggesting their critical role in determining different bacterial loads/phenotypes in SNPT and SPPT. Furthermore, some specific proteins were detected to be involved in the APC activation/acquired immune response, providing some promising therapeutic targets for TB. Conclusion: Our study provides valuable insights into the differential molecular mechanisms underlying SNPT and SPPT, reveals the critical role of antigen-presenting cell activation in SNPT for effectively clearing the majority of Mtb in bodies, and shows the possibility of APC activation as a novel TB treatment strategy.

Music recharges people: Synchronized music during aerobic exercise leads to better self-regulation performance.

Previous studies have demonstrated that music has a positive effect on individuals during exercise and sports. We speculate that one of the mechanisms for this positive effect may be that music reduces the consumption of self-regulation strength. The primary objective of this study was to use a self-regulation strength model to explain the impact of music on individuals during aerobic exercises. Specifically, we examined the effects of synchronous music on college students' depletion of self-regulation during aerobic exercises. The participants underwent a pre-test in which they had to maintain 50% maximum voluntary contraction (MVC) isometric grip and do exercise planning tasks. For subsequent power bicycle riding (aerobic exercise), the participants were divided into a music group and a control group. The music group performed aerobic exercises with synchronous music, while the control group performed aerobic exercises without music. After aerobic exercise, the participants underwent a post-test for isometric grip and exercise planning tasks. The results showed that the music group planned to reduce their efforts less for an upcoming exercise period (p < 0.01, d = 0.81), and their wrist flexor muscle group generated less electromyographic activation during an isometric grip task that maintained 50% MVC (p < 0.05, d = 0.80) than the control group. However, the two groups showed no difference in the duration of 50% MVC. This shows that: (a) for the same duration, participants in the music group required a lower degree of muscle activation than the control group, suggesting that music reduced the consumption of self-regulation strength in aerobic exercise; and (b) music decreased participants' planned exertion declined, also suggesting that music reduced the consumption of self-regulation strength in aerobic exercise.

The CK2 inhibitor CX4945 reverses cisplatin resistance in the A549/DDP human lung adenocarcinoma cell line.

Lung cancer negatively impacts global health, and the incidence of non-small cell lung cancer (NSCLC) is highest among all forms of lung cancer. Chemotherapy failure mainly occurs due to drug resistance; however, the associated molecular mechanism remains unclear. Casein kinase II (CK2), which plays important roles in the occurrence, development and metastasis of many tumours, regulates Wnt signaling by modulating ß-catenin expression. In the present study the effects of the CK2 inhibitor, CX4945 on cisplatin [or cis-diamminedichloroplatinum (II); (DDP)]-resistant A549 cells (A549/DDP) were investigated to elucidate the underlying molecular mechanism. A549/DDP cells were divided into four groups (blank control, CX4945, cisplatin and CX4945+cisplatin). Cisplatin resistance was 5.16-fold greater in A549/DDP cells compared with that in A549 cells, with an optimal cisplatin concentration of 5 µg/ml. Moreover, levels of CK2, dishevelled-2 (DVL-2) phosphorylated (p) at Ser143 (p-DVL-2Ser143), and major Wnt-signaling proteins were significantly higher in A549/DDP cells compared with that in A549 cells (P<0.05), with these levels further increased following cisplatin treatment (P<0.05), whereas these levels significantly decreased in A549 cells after cisplatin treatment (P<0.05). Additionally, multidrug-resistance-associated protein 1 and lung resistance protein expression was significantly higher in A549/DDP cells compared with that in A549 cells (P<0.05), with these levels increasing further in A549/DDP (P<0.05) but not A549 cells upon cisplatin treatment (P>0.05). In addition, reduced expression of resistance proteins in A549/DDP cells was accompanied by a decline in the 50% growth inhibition after CX4945 pre-treatment. Furthermore, levels of p-DVL-2Ser143 and major Wnt-signaling proteins decreased significantly after treatment of A549/DDP cells with CX4945+cisplatin, whereas DVL-2 and p-DVL-2Thr224 levels remained unchanged. Additionally, significant elevations in apoptosis rates in the CX4945+cisplatin group relative to the control and cisplatin-only groups, was observed (P<0.001). These results suggested that inhibiting Wnt/ß-catenin signaling with CX4945, which attenuates levels of drug-resistance-associated proteins and induces apoptosis, might reverse cisplatin resistance in NSCLC.

[Saikosaponin D inhibits proliferation and collagen production of human embryonic lung fibroblasts by regulating TGF-ß1/Smads signaling pathway].

Objective To investigate the effect of saikosaponin D (SSD) on the proliferation and transformation of human embryonic lung fibroblasts (HELFs) induced by transforming growth factor-beta 1 (TGF-ß1) and the regulation of signal pathway of TGF-ß1/Smads family. Methods HELFs were cultured in vitro and divided into 5 groups: a control group, 1 ng/mL TGF-ß1-induced group, 1 ng/mL TGF-ß1 combined with 0.5 µmol/L SSD treatment group, 1 ng/mL TGF-ß1 combined with 1 µmol/L SSD treatment group, and 1 ng/mL TGF-ß1 combined with 2 µmol/L SSD treatment group. Cell viability of HELFs was detected by CCK-8 assay. The expression of Smad2, Smad3 and Smad7 mRNA were detected by real-time fluorescence quantitative PCR. The protein levels of α-smooth muscle actin (α-SMA), type 1 collagen (Col1), Smad2, Smad3, phosphorylated Smad2 (p-smad2), p-smad3 and Smad7 were assessed by Western blot analysis. Results Compared with the control group, TGF-ß1-induced group showed the apparently increased proliferation ability, the increased protein levels of Col1 and α-SMA, the significantly increased mRNA and protein phosphorylation levels of Smad2 and Smad3, and the significantly decreased mRNA and protein expression of Smad7. Compared with the TGF-ß1-induced group, the cell proliferation of HELFs in different concentrations of SSD treatment groups was reduced, which could reverse the changes of the above indicators in a dose-dependent manner. Conclusion SSD plays an important role in anti-pulmonary fibrosis by regulating TGF-ß1/Smads signaling pathway.

[Effect of S-adenosylmethionine on vascular smooth cells proliferation and migration].

OBJECTIVE: To investigate the effect of S-adenosyl-L-methionine (SAMe) on vascular smooth muscle cells (VSMCs) proliferation and migration and neointima formation in rat carotid artery balloon injury model. METHODS: Rat VSMCs were divided into control group, TNF-α (10 ng/ml) group, SAMe (0.2 mmol/L) group and TNF-α + SAMe group. VSMC migration distance and proliferation were examined by cell scrape tests and MTT method. NF-κB activity was analyzed by EMSA. PDGF mRNA expression was detected by Northern blot. SD rat were divided into control group, carotid balloon injury group treated with saline or SAMe (15 mg×kg(-1)×d(-1) for 14 d), then blood vessel proliferation was observed histologically in rat carotid artery. RESULTS: (1) In vitro, the VSMCs migration distance, absorbance at 490 nm, PDGF mRNA expression, NF-κB activity were all increased in TNF-α group compared to the control group (P < 0.01), and decreased in TNF-α + SAMe group compared to the TNF-α group (P < 0.01). (2) In the balloon injury in vivo models, the intima area of saline group and SAMe group was increased compared to the control group, while the lumen area was larger and the intima area was smaller in the SAMe group than in the saline group (all P < 0.05). CONCLUSION: SAMe could reduce TNF-α induced VSMC proliferation and migration possibly through inhibiting NF-κB activity and downregulating PDGF gene expression.