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Stem cells can be used for regenerative medicine and as treatments for disease. The application of tissue engineering-related transplantation, stem cells, and local changes in the microenvironment is expected to solve major medical problems. Currently, most studies focus on tissue repair and regeneration, and mesenchymal stem cells (MSCs) are among the most common research topics. MSCs are applicable as seed cells, and they represent one of the current hot topics in regenerative medicine research. However, due to storage limitations and because cell senescence occurs during in vitro expansion, their clinical application is challenging. Exosomes, which are secreted by MSCs through paracrine signalling, not only have the same effects as MSCs, but they also have the advantages of targeted delivery, low immunogenicity, and high repairability. This article reviews the acquisition methods, characteristics, biological functions, and clinical applications of exosomes.

Long noncoding RNAs (lncRNAs) are emerging as a new class of important regulators of signal transduction in tissue homeostasis and cancer development. Liquid–liquid phase separation (LLPS) occurs in a wide range of biological processes, while its role in signal transduction remains largely undeciphered. In this study, we uncovered a lipid-associated lncRNA, small nucleolar RNA host gene 9 ( SNHG9 ) as a tumor-promoting lncRNA driving liquid droplet formation of Large Tumor Suppressor Kinase 1 (LATS1) and inhibiting the Hippo pathway. Mechanistically, SNHG9 and its associated phosphatidic acids (PA) interact with the C-terminal domain of LATS1, promoting LATS1 phase separation and inhibiting LATS1-mediated YAP phosphorylation. Loss of SNHG9 suppresses xenograft breast tumor growth. Clinically, expression of SNHG9 positively correlates with YAP activity and breast cancer progression. Taken together, our results uncover a novel regulatory role of a tumor-promoting lncRNA (i.e., SNHG9 ) in signal transduction and cancer development by facilitating the LLPS of a signaling kinase (i.e., LATS1).

Cytokine storm resulting from SARS-CoV-2 infection is one of the leading causes of acute respiratory distress syndrome (ARDS) and lung fibrosis. We investigated the effect of inflammatory molecules to identify any marker that is related to lung fibrosis in coronavirus disease 2019 (COVID-19). Seventy-six COVID-19 patients who were admitted to Youan Hospital between January 21 and March 20, 2020 and recovered were recruited for this study. Pulmonary fibrosis, represented as fibrotic volume on chest CT images, was computed by an artificial intelligence (AI)-assisted program. Plasma samples were collected from the participants shortly after admission, to measure the basal inflammatory molecules levels. At discharge, fibrosis was present in 46 (60.5%) patients whose plasma interferon-γ (IFN-γ) levels were twofold lower than those without fibrosis ( > 0.05). The multivariate-adjusted logistic regression analysis demonstrated the inverse association risk of having lung fibrosis and basal circulating IFN-γ levels with an estimate of 0.43 ( = 0.02). Per the 1-SD increase of basal IFN-γ level in circulation, the fibrosis volume decreased by 0.070% ( = 0.04) at the discharge of participants. The basal circulating IFN-γ levels were comparable with c-reactive protein in the discrimination of the occurrence of lung fibrosis among COVID-19 patients at discharge, unlike circulating IL-6 levels. In conclusion, these data indicate that decreased circulating IFN-γ is a risk factor of lung fibrosis in COVID-19.

A principal goal of cancer nanomedicine is to deliver therapeutics effectively to cancer cells within solid tumors. However, there are a series of biological barriers that impede nanomedicine from reaching target cells. Here, we report a stimuli-responsive clustered nanoparticle to systematically overcome these multiple barriers by sequentially responding to the endogenous attributes of the tumor microenvironment. The smart polymeric clustered nanoparticle (iCluster) has an initial size of ∼100 nm, which is favorable for long blood circulation and high propensity of extravasation through tumor vascular fenestrations. Once iCluster accumulates at tumor sites, the intrinsic tumor extracellular acidity would trigger the discharge of platinum prodrug-conjugated poly(amidoamine) dendrimers (diameter ∼5 nm). Such a structural alteration greatly facilitates tumor penetration and cell internalization of the therapeutics. The internalized dendrimer prodrugs are further reduced intracellularly to release cisplatin to kill cancer cells. The superior in vivo antitumor activities of iCluster are validated in varying intractable tumor models including poorly permeable pancreatic cancer, drug-resistant cancer, and metastatic cancer, demonstrating its versatility and broad applicability.

Investigate the mechanism of how sodium butyrate (NaBut) improves mitochondrial function and kidney tissue injury in diabetic kidney disease (DKD) the AMPK/PGC-1α pathway. Assess the effects of NaBut on glucose and insulin tolerance, urine, and gut microbial composition in db/db and db/m mice. Use flow cytometry and western blotting to detect the effects of NaBut on apoptosis, kidney mitochondrial function, and AMPK/PGC-1α signaling. Use HK-2 cells induced by high glucose (HG) to establish the DKD model and detect changes in the AMPK/PGC-1α signaling pathway and mitochondrial function after NaBut intervention. NaBut attenuated blood glucose levels and reversed increases in urine and serum levels of glucose, BUN, Ucr, TG, TC, and UAE in db/db mice. NaBut improved insulin tolerance, reversed PGC-1α and p-AMPK expression level in the kidneys of db/db mice, and improved lipid accumulation and mitochondrial function. NaBut was able to reverse the effects of elevated glucose, compound C, and siRNA-PGC on ROS and ATP levels. Additionally, it increased protein expression of PGC-1α and p-AMPK. NaBut activates the kidney mitochondrial AMPK/PGC-1α signaling pathway and improves mitochondrial dysfunction in DKD, thus protecting kidney tissue and .

Iron metabolism dysregulation is tightly associated with cancer development. But the underlying mechanisms remain poorly understood. Increasing evidence has shown that long noncoding RNAs (lncRNAs) participate in various metabolic processes via integrating signaling pathway. In this study, we revealed one iron-triggered lncRNA, one target of YAP, LncRIM (LncRNA Related to Iron Metabolism, also named ZBED5-AS1 and Loc729013 ), which effectively links the Hippo pathway to iron metabolism and is largely independent on IRP2. Mechanically, LncRIM directly binds NF2 to inhibit NF2-LATS1 interaction, which causes YAP activation and increases intracellular iron level via DMT1 and TFR1. Additionally, LncRIM -NF2 axis mediates cellular iron metabolism dependent on the Hippo pathway. Clinically, high expression of LncRIM correlates with poor patient survival, suggesting its potential use as a biomarker and therapeutic target. Taken together, our study demonstrated a novel mechanism in which LncRIM- NF2 axis facilitates iron-mediated feedback loop to hyperactivate YAP and promote breast cancer development. Iron metabolism dysregulation is associated with various diseases including cancer. Here, the authors show that one iron-triggered lncRNA LncRIM regulates cellular iron metabolism effectively by wiring up the Hippo-YAP  signaling pathway and promotes breast cancer development.

This study examines the effects of rapid rehabilitation on surgical site wound infections and pain in patients with intertrochanteric femoral fractures. A computerised search was conducted for randomised controlled trials (RCTs) on rapid rehabilitation care in patients undergoing surgery for intertrochanteric femoral fractures published in the China National Knowledge Infrastructure, China Biomedical Literature Database, Wanfang Database, VIP, PubMed, Embase, Cochrane Library and Web of Science. The search was conducted from the time of the database construction to August 2023. Two investigators independently performed literature screening, data extraction and quality assessment based on predefined inclusion and exclusion criteria. Meta‐analysis was performed via RevMan 5.4 software. Encompassing 21 studies involving 2004 patients, with 1007 patients receiving rapid rehabilitation care and 997 receiving routine care, our analysis revealed that rapid rehabilitation care significantly reduced postoperative complications (odds ratio [OR] = 0.24, 95% confidence interval [CI]: 0.17–0.33, p < 0.001), wound infections (OR = 0.30, 95% CI: 0.14–0.65, p = 0.002) and hospital stay (mean difference [MD] = −5.23, 95% CI: −6.03 to −4.43, p < 0.001). Moreover, compared with routine care, it notably improved wound pain (MD = −1.51, 95% CI: −1.98 to −1.05, p < 0.001) in patients undergoing surgery for intertrochanteric femoral fractures. Our findings underscore the effectiveness of rapid rehabilitation care in reducing wound pain, postoperative complications and wound infections among patients with intertrochanteric femoral fractures.

Periostin (POSTN) is an extracellular matrix (ECM) protein, involved in various diseases. This research focused on the detailed mechanisms study of periostin (POSTN) overexpression in renal cell carcinoma (RCC) invasion and migration. Western blot and RT-PCR were performed to explore POSTN expression in various RCC cells. Cells were transfected with siRNAs or lentivirus to regulate the expression of POSTN. The effects of POSTN on cell viability, apoptosis, migration, invasion and epithelial-to-mesenchymal transition (EMT) of RCC cells were determined by CCK-8, flow cytometry, migration and invasion assay and Western blot analysis. POSTN expression was significantly enhanced in RCC cells compared with renal tubular epithelial cells. In vitro experiments showed that POSTN knockdown could dramatically inhibit RCC cell proliferation, migration and invasion, while overexpression of POSTN could promote these biological behaviors. We further demonstrated that POSTN knockdown suppressed epithelial-mesenchymal transition (EMT), which was mediated via upregulation of E-cadherin and downregulation of N-cadherin and vimentin, through IKL/AKT/mTOR pathway. In contrast, overexpression of POSTN could promote EMT in RCC cells via the activation of IKL /AKT/mTOR pathway. Next, we demonstrated that higher POSTN expression promoted angiogenesis in vivo in an RCC xenograft tumor via activating IKL /AKT/mTOR pathway. Our study showed that POSTN could promote EMT through ILK/AKT/mTOR pathway and might be an alternative therapeutic strategy for RCC treatment.

Background Rheumatoid arthritis (RA) is a systemic and chronic inflammatory disease. The cellular glucose metabolism of fibroblast‐like synoviocytes (FLSs) of RA has been revealed to be essential to the pathogenesis and development of RA. To date, the precise roles and molecular mechanisms of long noncoding RNA TUG1 in RA have not been elucidated. Methods TUG1 and miR‐34a‐5p were detected by qRT‐PCR. Interactions between lncRNA‐miRNA and miRNA‐mRNA were validated by RNA pull‐down assay and luciferase assay. The glucose metabolism was evaluated by glucose uptake and extracellular acidification rate (ECAR). Cell viability was determined by MTT assay and Annexin V assay. Results TUG1 expression was significantly upregulated in synovial fibroblast‐like synoviocytes (FLSs) compared with normal FLSs. Functional assays uncovered that silence of TUG1 suppressed FLSs‐RA invasion, migration, glucose metabolism, and increased apoptosis. Bioinformatics analysis indicated that TUG1 interacted with miR‐34a‐5p. RNA pull‐down assay and luciferase assay validated that TUG1 sponged miR‐34a‐5p in FLSs‐RA. Overexpression of miR‐34a‐5p effectively inhibited glucose metabolism of FLSs‐RA. Furthermore, the glucose metabolism of FLSs‐RA was significantly elevated compared with normal FLSs. The glucose metabolism enzyme, LDHA, was directly targeted by miR‐34a‐5p in FLSs. Rescue experiments validated that the miR‐34a‐5p‐inhibited glucose metabolism of FLSs‐RA was through targeting LDHA. Finally, we showed restoration of miR‐34a‐5p in TUG1‐overexpressing FLSs‐RA successfully overcame the TUG1‐promoted glucose metabolism and apoptosis resistance via targeting LDHA. Conclusion The present study uncovered critical roles and molecular mechanisms underlying the TUG1‐mediated glucose metabolism and apoptosis of FLSs‐RA through modulating the miR‐34a‐5p‐LDHA pathway in fibroblast‐like synoviocytes of rheumatoid arthritis. Our conclusions uncover critical roles and molecular mechanisms of the TUG1‐mediated glucose metabolism and apoptosis of FLSs‐RA through modulating the miR‐34a‐5p‐LDHA pathway in RA patients, suggesting that targeting TUG1 could be an effective therapeutic approach to suppress the proliferation of FLSs for rheumatoid arthritis treatment.

Background Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease; cellular glutamine metabolism in fibroblast-like synoviocytes (FLSs) of RA was known to be essential for RA pathogenesis and progression. NEAT1, a long non-coding RNA, functions as an oncogene in diverse cancers. The exact roles and molecular mechanisms of NEAT1 in fibroblast-like synoviocytes (FLSs) of RA patients are unknown. Methods Expression of NEAT1 and miR-338-3p was measured by qRT-PCR. lncRNA-miRNA and miRNA-mRNA interactions were predicted from starBase and validated by RNA pull-down and luciferase assay. The glutamine metabolism of FLSs was evaluated by glutamine uptake and glutaminase activity. Cell death in FLSs in response to H 2 O 2 was assessed by MTT and Annexin V assays. Results NEAT1 was significantly upregulated, and miR-338-3p was significantly downregulated in FLSs from RA patients compared to normal FLSs. Silencing of NEAT1 and overexpression of miR-338-3p suppressed glutamine metabolism in FLSs-RA and promoted H 2 O 2 -induced apoptosis. Bioinformatics analysis showed that NEAT1 sponges miR-338-3p to form competing endogenous RNA (ceRNAs), which was verified by RNA pull-down assay and luciferase assay FLSs-RA had an increased rate of glutamine metabolism compared to normal FLSs increased compared to normal FLSs. The results confirmed that GLS (Glutaminase), a key enzyme in glutamine metabolism, is a direct target of miR-338-3p in FLSs-RA. miR-338-3p inhibition of glutamine metabolism was verified by rescue experiments verified. Finally, restoration of miR-338-3p in FLSs-RA expressing NEAT1 overcomes NEAT1-promoted glutamine metabolism and resistance to apoptosis. Conclusions This study reveals the essential role and molecular targets of NEAT1-regulated glutamine metabolism and FLSs-RA dysfunction in fibroblast-like synoviocytes of RA and indicates that blocking the molecular pathway via non-coding RNAs may be beneficial for RA patients.