Individuals who experience myocardial infarction (MI) often experience anxiety. Green tea has potent antioxidative properties and, epigallocatechin-3-gallate (EGCG), which is a primary component of tea polyphenols, has advantageous effects on anxiety and depression. However, its mechanism of action regarding the inhibition of anxiety-like symptoms after MI remains unclear. This study examined whether EGCG alleviated anxiety-like behavior in MI rats and its possible mechanism.

More than 40% of lung cancers are lung adenocarcinoma (LUAD) worldwide. However, the prognosis of LUAD is poor for the lack of effective treatment methods. Our study identified PLK1 as a novel prognosis biomarker and treatment target for LUAD. Based on the Cancer Genome Atlas (TCGA) database, differentially expressed genes (DEGs) from 551 LUAD cases were analyzed for the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. To explore the biological pathways and the tumor-infiltrating immune cells (TICs) using gene set variation analysis (GSVA) and the CIBERSORT, as well as to analyze DEGs, a protein-protein interaction (PPI) network and Cox regression analysis were performed. Validation of DEGs was achieved through quantitative real-time PCR (qPCR) and immunoblotting. DEGs associated with the cell cycle were sorted out. Cell cycle scores were positively correlated with age, clinical stages, and metastasis and negatively correlated with overall survival of LUAD patients. PPI and Cox analyses showed that PLK1 could be a prognostic factor for LUAD patients. CIBERSORT analysis revealed a positive correlation between the transcription level of PLK1 and the function of CD8+ and activated memory CD4+ T cells, as well as a negative correlation with activated natural killer cells. Furthermore, PLK1 overexpression increased immune cytotoxicity, as measured by the cytolytic activity score, IFN- score, and IFN- level. There is a strong correlation between PLK1 and key features of TICs, indicating its potential as a promising prognostic biomarker for LUAD.

Propionibacterium acnes (P. acnes) has been implicated in the progression of acne inflammation. Because current acne medications have various side effects, it is necessary to explore alternative medications possessing anti-inflammatory activity against P. acnes. We investigated the inhibitory effects of polyphyllin I (PPI) on P. acnes-induced inflammation in vitro. In this study, we examined the effects of PPI on the production of inflammatory cytokines in HaCaT keratinocytes treated with heat-killed P. acnes. These treated HaCaT keratinocytes showed increased expression of Toll-like receptor 2 (TLR2) and production of inflammatory cytokines. PPI significantly suppressed the secretion of inflammatory cytokines, including interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α, and the expression of TLR2 in P. acnes-treated cells. Moreover, we studied the influence of PPI on the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in P. acnes-treated keratinocytes. PPI diminished the activation of NF-κB. Phosphorylated p38 levels were markedly increased after treatment with heat-killed P. acnes but were decreased after treatment with PPI, while the effect of PPI on ERK phosphorylation was not significant. Heat-killed P. acnes and PPI did not have any effect on JNK phosphorylation. Furthermore, we confirmed that NF-κB p65 inhibitor (BAY11-7082), p38 MAPK inhibitor (SB203580), and PPI blocked the expression of IL-8 in heat-killed P. acnes-treated cells. These results demonstrated that PPI has potential for development as a treatment for acne inflammation.

Bone marrow mesenchymal stem cell (BMSC) transplantation is effective for repairing spinal cord injuries (SCIs); however, there are limitations of clinical BMSC applications. Previously, we reported that dermal papilla cells (DPCs) secrete brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor more actively than BMSCs. To analyze the therapeutic function of DPCs in SCI, primary DPCs and BMSCs were cultured from the same green fluorescence protein-transgenic rat. The cells were suspended in rat-tail collagen I and transplanted separately into completely transected spinal cord lesion sites. Grafted-cell survival was examined with a small animal in vivo imaging detection system, and lesion sites were examined histochemically. In vivo imaging revealed enhanced lesion filling and survival with DPC grafts compared with BMSC grafts on days 14 and 21 post-transplantation. Hematoxylin and eosin staining demonstrated that lesion area sizes in the two groups were not markedly different. In the DPC transplant group, more axons formed within the lesion sites. CD31-positive vessel-like structures were more abundant in lesion sites near the grafted cells in the DPC group. The results of the present study suggest that DPCs may be a valuable alternative source of stem cells for autologous cell therapy for the treatment of SCI.

MicroRNAs (miRNAs) play an essential role in articular cartilage development and growth. However, the exact mechanisms involved in this process remain unknown. In the present study, we investigated the biological functions of miR-27b during hypertrophic differentiation of rat articular chondrocytes. Based on in situ hybridization and immunohistochemistry, we report that miR-27b expression is reduced in the hypertrophic zone of articular cartilage, but expression of peroxisome proliferator-activated receptor γ (Pparγ) is increased. Dual-luciferase reporter gene assay and Western blot analysis demonstrated that Pparγ2 is a target of miR-27b Overexpression of miR-27b inhibited expression of Pparγ2, as well as type X collagen (Col10a1) and matrix metalloproteinase 13 (Mmp13), while significantly promoting the expression of Sex-determining Region-box 9 (Sox9) and type II collagen (Col2a1) at both the mRNA and protein levels. Rosiglitazone, a Pparγ agonist, suppressed Col2a1 expression, while promoting expression of runt-related transcription factor 2 (Runx2) and Col10a1 in a concentration-dependent manner. siRNA-mediated knockdown of Pparγ2 caused an increase in protein levels of Col2a1. The present study demonstrates that miR-27b regulates chondrocyte hypertrophy in part by targetting Pparγ2, and that miR-27b may have important therapeutic implications in cartilage diseases.

The Sec61/SecY channel allows the translocation of many proteins across the eukaryotic endoplasmic reticulum membrane or the prokaryotic plasma membrane. In bacteria, most secretory proteins are transported post-translationally through the SecY channel by the SecA ATPase. How a polypeptide is moved through the SecA-SecY complex is poorly understood, as structural information is lacking. Here, we report an electron cryo-microscopy (cryo-EM) structure of a translocating SecA-SecY complex in a lipid environment. The translocating polypeptide chain can be traced through both SecA and SecY. In the captured transition state of ATP hydrolysis, SecA's two-helix finger is close to the polypeptide, while SecA's clamp interacts with the polypeptide in a sequence-independent manner by inducing a short β-strand. Taking into account previous biochemical and biophysical data, our structure is consistent with a model in which the two-helix finger and clamp cooperate during the ATPase cycle to move a polypeptide through the channel.

Glioblastoma (GBM) is the most prevalent and aggressive type of brain tumor in the central nervous system. Clinical outcomes for patients with GBM are unsatisfactory. Here, we aimed to identify novel, reliable prognostic factors for GBM. Cox and interactive analyses were used to identify hub genes from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets. After validation using various cohorts, survival analysis, meta-analysis, and prognostic analysis were performed. Coexpression and enrichment analyses were performed to elucidate the biological pathways of hub genes involved in GBM. ESTIMATE and CIBERSORT methods were applied to analyze the association of hub genes with the tumor microenvironment (TME). Paxillin (PXN) was identified as a hub gene with a high expression in GBM. PXN expression was negatively correlated with overall survival, progression-free survival, and disease-free survival in patients with GBM. Meta-analysis and Cox analysis revealed that PXN could act as an independent prognostic factor in GBM. In addition, PXN was significantly coexpressed with signal transducer and activator of transcription 3 and transforming growth factor β1 and participated in focal adhesion, extracellular matrix/receptor interactions, and the phosphatidylinositol 3-kinase/AKT signaling pathway. The results of ESTIMATE and CIBERSORT analyses revealed that PXN was implicated in TME alterations, particularly the infiltration of regulatory T cells, activated memory T cells, and activated natural killer cells. PXN may be a reliable prognostic factor for GBM. Further studies are needed to validate these findings.

Background: Stomach adenocarcinoma (STAD) is the fourth highest cause of cancer mortality worldwide. Alterations in copper metabolism are closely linked to cancer genesis and progression. We aim to identify the prognostic value of copper metabolism-related genes (CMRGs) in STAD and the characteristic of the tumor immune microenvironment (TIME) of the CMRG risk model. Methods: CMRGs were investigated in the STAD cohort from The Cancer Genome Atlas (TCGA) database. Then, the hub CMRGs were screened out with LASSO Cox regression, followed by the establishment of a risk model and validated by GSE84437 from the Expression Omnibus (GEO) database. The hub CMRGs were then utilized to create a nomogram. TMB (tumor mutation burden) and immune cell infiltration were investigated. To validate CMRGs in immunotherapy response prediction, immunophenoscore (IPS) and IMvigor210 cohort were employed. Finally, data from single-cell RNA sequencing (scRNA-seq) was utilized to depict the properties of the hub CMRGs. Results: There were 75 differentially expressed CMRGs identified, 6 of which were linked with OS. 5 hub CMRGs were selected by LASSO regression, followed by construction of the CMRG risk model. High-risk patients had a shorter life expectancy than those low-risk. The risk score independently predicted STAD survival through univariate and multivariate Cox regression analyses, with ROC calculation generating the highest results. This risk model was linked to immunocyte infiltration and showed a good prediction performance for STAD patients' survival. Furthermore, the high-risk group had lower TMB and somatic mutation counters and higher TIDE scores, but the low-risk group had greater IPS-PD-1 and IPS-CTLA4 immunotherapy prediction, indicating a higher immune checkpoint inhibitors (ICIs) response, which was corroborated by the IMvigor210 cohort. Furthermore, those with low and high risk showed differential susceptibility to anticancer drugs. Based on CMRGs, two subclusters were identified. Cluster 2 patients had superior clinical results. Finally, the copper metabolism-related TIME of STAD was concentrated in endothelium, fibroblasts, and macrophages. Conclusion: CMRG is a promising biomarker of prognosis for patients with STAD and can be used as a guide for immunotherapy.

The identification of prognostic and therapeutic biomarkers is essential to reduce morbidity and mortality from lung adenocarcinoma (LUAD). This study aimed to identify a reliable prognostic and therapeutic biomarker for LUAD using integrated bioinformatics. Based on the cancer genome atlas (TCGA) and genome-tissue expression (GTEx) analyses, KIF20A has been identified as the hub gene. Following validation using a series of cohorts, survival analysis, meta-analysis, and univariate Cox analysis was conducted. ESTIMATE and CIBERSORT algorithms were then used to study the association of KIF20A with the tumor microenvironment (TME) and the percentage of tumor-infiltrating immune cells (TICs). In vitro experiments were conducted to determine the function of KIF20A. Finally, there was a negative association between the expression of the KIF20A and overall survival, progression-free survival, and disease-free survival, which was confirmed by meta-analysis and COX analysis. Furthermore, KIF20A also had a potential role of altering the TME and TICs proportions in LUAD. Validations in vitro were performed on A549 and PC-9 cell lines, and we found that the knockdown of KIF20A exhibited inhibitory effects on cell proliferation, resulted in cell cycle arrest during the G2/M phase, and induced cellular apoptosis. Our study demonstrated that KIF20A could be utilized as a reliable prognostic marker and treatment target for LUAD. However, further studies are required to validate these findings.

Autologous chondrocyte implantation (ACI) is an effective method for treating chronic articular cartilage injury and degeneration; however, it requires large numbers of hyaline chondrocytes, and human hyaline chondrocytes often undergo dedifferentiation in vitro. Moreover, although long non-coding RNAs (lncRNAs) regulate gene expression in many pathological and physiological processes, their role in human hyaline chondrocyte dedifferentiation remains unclear. Here, we examined lncRNA and mRNA expression profiles in human hyaline chondrocyte dedifferentiation using microarray analysis. Among the many lncRNAs and mRNAs that showed differential expression, lncRNA AP001505.9 (ENST00000569966) was significantly downregulated in chondrocytes after dedifferentiation. We next performed gene ontology, pathway, and CNC (coding-non-coding gene co-expression) analyses to investigate potential regulatory mechanisms for AP001505.9. Pellet cultures were then used to redifferentiate dedifferentiated chondrocytes, and AP001505.9 expression was upregulated after redifferentiation. Finally, both in vitro and in vivo experiments demonstrated that AP001505.9 overexpression inhibited dedifferentiation of chondrocytes. This study characterizes lncRNA expression profiles in human hyaline chondrocyte dedifferentiation, thereby identifying new potential mechanisms of chondrocyte dedifferentiation worthy of further investigation.

The process of intracellular proteolysis through ATP-dependent proteases is a biologically conserved phenomenon. The stress responses and bacterial virulence of various pathogenic bacteria are associated with the ATP-dependent Clp protease. In this study, a Brucella abortus 2308 strain, ΔclpP, was constructed to characterize the function of ClpP peptidase. The growth of the ΔclpP mutant strain was significantly impaired in the TSB medium. The results showed that the ΔclpP mutant was sensitive to acidic pH stress, oxidative stress, high temperature, detergents, high osmotic environment, and iron deficient environment. Additionally, the deletion of clpP significantly affected Brucella virulence in macrophage and mouse infection models. Integrated transcriptomic and proteomic analyses of the ΔclpP strain showed that 1965 genes were significantly affected at the mRNA and/or protein levels. The RNA-seq analysis indicated that the ΔclpP strain exhibited distinct gene expression patterns related to energy production and conversion, cell wall/membrane/envelope biogenesis, carbohydrate transport, and metabolism. The iTRAQ analysis revealed that the differentially expressed proteins primarily participated in amino acid transport and metabolism, energy production and conversion, and secondary metabolites biosynthesis, transport and catabolism. This study provided insights into the preliminary molecular mechanism between Clp protease to bacterial growth, stress response, and bacterial virulence in Brucella strains.

Hair loss, including alopecia, is a common and distressing problem for men and women, and as a result, there is considerable interest in developing treatments that can prevent or reverse hair loss. Dermal papillae closely interact with epidermal cells and play a key role during hair follicle induction and hair morphogenesis. As dermal papilla cells (DPCs) lose their hair‑inducing ability in monolayer cultures in vitro, it is difficult to obtain de novo hair follicle structures following DPC transplantation in vivo. The present study aimed to explore culture conditions to maintain DPC characteristics using conditioned media (CM) from the supernatant of cultured HaCaT keratinocyte cells supplemented with other components. Initially, it was observed that during passaging of in vitro monolayer DPC cultures, the Wnt/β‑catenin pathway was repressed, while the TGF‑β/Smad pathway was activated, and that HaCaT cells cultivated in 1% fetal bovine serum had higher levels of expression of Wnt3a and Wnt10b compared with normal keratinocytes. Culturing of high‑passage (P7) DPCs in CM from HaCaT cells (HaCaT‑CM) actively stimulated cell proliferation and maintained Sox2 and Versican expression levels. Supplementation of HaCaT‑CM with SB431542 (SB, a TGF‑β receptor inhibitor), CHIR99021, (CHIR, a GSK3α/β inhibitor and activator of Wnt signaling) and platelet‑derived growth factor (PDGF)‑AA further increased the expression levels of Sox2, Versican and alkaline phosphatase (ALP) in P7 DPCs. Three‑dimensional culture of P7 DPCs using hanging drop cultures in HaCaT‑CM supplemented with SB, CHIR and PDGF‑AA resulted in larger cell aggregates and a further significant upregulation of Sox2, ALP and Versican expression levels. Taken together, these findings demonstrated that HaCaT‑CM supplemented with SB, CHIR and PDGF‑AA may preserve the hair‑inducing ability of high‑passage DPCs and may therefore be useful in reconstructing new hair follicles in vivo.