Enormous studies have corroborated that long non-coding RNAs (lncRNAs) extensively participate in crucial physiological processes such as metabolism and immunity, and are closely related to the occurrence and development of tumors, cardiovascular diseases, nervous system disorders, nephropathy, and other diseases. The application of lncRNAs as biomarkers or intervention targets can provide new insights into the diagnosis and treatment of diseases. This paper has focused on the emerging research into lncRNAs as pharmacological targets and has reviewed the transition of lncRNAs from the role of disease coding to acting as drug candidates, including the current status and progress in preclinical research. Cutting-edge strategies for lncRNA modulation have been summarized, including the sources of lncRNA-related drugs, such as genetic technology and small-molecule compounds, and related delivery methods. The current progress of clinical trials of lncRNA-targeting drugs is also discussed. This information will form a latest updated reference for research and development of lncRNA-based drugs.

Glioblastoma is an aggressive tumor that is associated with distinctive infiltrating microglia/macrophages populations. Previous studies demonstrated that chlorogenic acid (5-caffeoylquinic acid, CHA), a phenolic compound with low molecular weight, has an anti-tumor effect in multiple malignant tumors. In the present study, we focused on the macrophage polarization to investigate the molecular mechanisms behind the anti-glioma response of CHA in vitro and in vivo. We found that CHA treatment increased the expression of M1 markers induced by LPS/IFNγ, including iNOS, MHC II (I-A/I-E subregions) and CD11c, and reduced the expression of M2 markers Arg and CD206 induced by IL-4, resulting in promoting the production of apoptotic-like cancer cells and inhibiting the growth of tumor cells by co-culture experiments. The activations of STAT1 and STAT6, which are two crucial signaling events in M1 and M2-polarization, were significantly promoted and suppressed by CHA in macrophages, respectively. Furthermore, In G422 xenograft mice, CHA increased the proportion of CD11c-positive M1 macrophages and decreased the distribution of CD206-positive M2 macrophages in tumor tissue, consistent with the reduction of tumor weight observed in CHA-treated mice. Overall these findings indicated CHA as a potential therapeutic approach to reduce glioma growth through promoting M1-polarized macrophage and inhibiting M2 phenotypic macrophage.

Tumor-associated macrophages (TAMs) generally display an immunosuppressive M2 phenotype and promote tumor progression and metastasis, suggesting their potential value as a target in cancer immunotherapy. Chlorogenic acid (CHA) has been identified as a potent immunomodulator that promotes the polarization of TAMs from an M2 to an M1 phenotype. However, rapid clearance in vivo and low tumor accumulation have compromised the immunotherapeutic efficacy of CHA in clinical trials. In this study, mannosylated liposomes are developed for targeted delivery of CHA to TAMs. The immunoregulatory effects of CHA, along with the overall antitumor efficacy of CHA-encapsulated mannosylated liposomes, are investigated through in vitro and in vivo experiments. The prepared CHA-encapsulated mannosylated liposomes exhibit an ideal particle size, favorable stability, and preferential accumulation in tumors via the mannose receptor-mediated TAMs-targeting effects. Further, CHA-encapsulated mannosylated liposomes inhibit G422 glioma tumor growth by efficiently promoting the polarization of the pro-tumorigenic M2 phenotype to the anti-tumorigenic M1 phenotype. Overall, these findings indicate that CHA-encapsulated mannosylated liposomes have great potential to enhance the immunotherapeutic efficacy of CHA by inducing a shift from the M2 to the M1 phenotype.

Skin aging is categorized as chronological aging and photo-aging that affected by intrinsic and extrinsic factors. The present study aimed to investigate the anti-aging ability and its underlying mechanism of chlorogenic acid (CGA) on human dermal fibroblasts (HDFs). In this study, CGA specifically up-regulated collagen I (Col1) mRNA and protein expressions and increased the collagen secretion in the supernatant of HDFs without affecting the cell viability, the latter was also demonstrated in BioMAP HDF3CGF system. Under ultraviolet A (UVA)-induced photoaging, CGA regulated collagen metabolism by increasing Col1 expression and decreasing matrix metalloproteinase 1 (MMP1) and MMP3 levels in UVA-irradiated HDFs. The activation of transforming growth factor-β (TGF-β)-mediated Smad2/3 molecules, which is crucial in Col1 synthesis, was suppressed by UVA irradiation and but enhanced at the presence of CGA. In addition, CGA reduced the accumulation of UVA-induced reactive oxygen species (ROS), attenuated the DNA damage and promoted cell repair, resulting in reducing the apoptosis of UVA-irradiated HDFs. In conclusion, our study, for the first time, demonstrate that CGA has protective effects during skin photoaging, especially triggered by UVA-irradiation, and provide rationales for further investigation of CGA being used to prevent or treat skin aging.

Background: Septic acute kidney injury (AKI) causes high mortality in critical care units, and no effective therapy exists in clinical treatment. In the current study, water and ethanol extracts of Hydrangea paniculata (HP), a traditional Chinese medicinal plant, were used to test its renoprotective effects in a lipopolysaccharide (LPS)-induced murine model of septic AKI. Methods: C57BL/6 mice were orally pretreated with HP three times, and then intraperitoneal LPS injection was used to induce septic AKI. Blood from animals was collected for biochemical analysis and kidneys were obtained for pathological analysis. Kidney tissue homogenates were used to investigate the effect of HP on inflammation and oxidative stress. Immunohistochemistry was used to investigate tubular cell apoptosis. Flow cytometry was conducted to analyze leukocyte infiltration into the kidneys. Blood cell counts were used to analyze changes in peripheral leukocytes. In vitro studies with Ana1 and HK-2 cells stimulated by LPS were used to investigate the anti-inflammatory effects and inhibition of signaling pathways by HP. Results: HP significantly decreased blood urea nitrogen and plasma neutrophil gelatinase-associated lipocalin concentrations, as well as tubulointerstitium injuries in septic AKI mice. Moreover, HP administration improved animal survival following lethal LPS injections. HP ameliorated apoptosis of tubular cells by inhibiting the cleavage of caspase 3 and caspase 7. HP also showed pronounced antioxidant activity in AKI kidneys. HP showed anti-inflammatory effects by inhibiting the infiltration of neutrophils and macrophages into kidney tissues induced by LPS, as well as inhibiting the production of cytokines and chemokines. Possible molecular mechanisms included HP inhibition of NF-κB nuclear translocation in LPS-induced macrophages and tubular cells, and reduction of STAT3, STAT1, and ERK1/2 phosphorylation stimulated by LPS in vitro. Single acute toxicity tests confirmed that HP, even at 5 g/kg dosage, does not cause animal death. Pharmacokinetics also showed that coumarins from HP could be metabolized into two bioactive compounds, umbelliferone, and esculetin. Conclusions: HP extract may protect renal function in LPS-induced AKI by anti-inflammatory and antioxidant activities, and has potential in the critical care of AKI.