Multi-Targeted and On-Demand Non-Coding RNA Regulation Nanoplatform against Metastasis and Recurrence of Triple-Negative Breast Cancer.

Dysregulation of microRNAs (miRs) is the hallmark of triple-negative breast cancer (TNBC), which is closely involved with its growth, metastasis, and recurrence. Dysregulated miRs are promising targets for TNBC therapy, however, targeted and accurate regulation of multiple disordered miRs in tumors is still a great challenge. Here, a multi-targeting and on-demand non-coding RNA regulation nanoplatform (MTOR) is reported to precisely regulate disordered miRs, leading to dramatical suppression of TNBC growth, metastasis, and recurrence. With the assistance of long blood circulation, ligands of urokinase-type plasminogen activator peptide and hyaluronan located in multi-functional shells enable MTOR to actively target TNBC cells and breast cancer stem cell-like cells (BrCSCs). After entering TNBC cells and BrCSCs, MTOR is subjected to lysosomal hyaluronidase-induced shell detachment, leading to an explosion of the TAT-enriched core, thereby enhancing nuclear targeting. Subsequently, MTOR could precisely and simultaneously downregulate microRNA-21 expression and upregulate microRNA-205 expression in TNBC. In subcutaneous xenograft, orthotopic xenograft, pulmonary metastasis, and recurrence TNBC mouse models, MTOR shows remarkably synergetic effects on the inhibition of tumor growth, metastasis, and recurrence due to its on-demand regulation of disordered miRs. This MTOR system opens a new avenue for on-demand regulation of disordered miRs against growth, metastasis, and recurrence of TNBC.

Therapeutic Strategies for Postherpetic Neuralgia: Mechanisms, Treatments, and Perspectives.

PURPOSE OF REVIEW: Postherpetic neuralgia is an annoying pain that mainly affects older people. In order to give patients more options, this review summarizes the pharmacological and interventional treatments for postherpetic neuralgia and updates the research on the efficacy, thereby providing doctors with more treatment options. The adverse effects and effective doses of its various treatments are also presented so that the therapy can be prescribed according to their concrete physical conditions. In a word, this review is dedicated to providing a comprehensive overview of the treatment options for postherpetic neuralgia and offering patients more choices. RECENT FINDINGS: Combinational therapy is more excellent than monotherapy. The local anesthesia and gabapentin comprised outstanding compatibility. In addition, two therapeutic tools for PHN patients, especially for the intractable ones, electroacupuncture (EA), and osteopathic manipulative treatment (OMT), show their efficacy and become potential options to alleviate pain. In terms of treatment, guidelines recommend patients use tricyclic antidepressants (TCAs), gabapentin, pregabalin, and 5% lidocaine patches as the first-line medications, and gabapentin is investigated most, especially the gabapentin enacarbil (GEn). And drug efficacy can be limited by adverse effects and tolerated doses. Interventional treatments, with their invasiveness and operational difficulty, are usually considered for intractable patients. Combinational therapies may be used when a single therapy cannot achieve the desired effect. Therapies such as OMT and EA have also been proposed to palliate pain in some cases, and future directions of treatment may be investigated in Chinese medicine and acupuncture.

Regulatory function of DNA methylation mediated lncRNAs in gastric cancer.

As one of the most common malignancies worldwide, gastric cancer contributes to cancer death with a high mortality rate partly responsible for its out-of-control progression as well as limited diagnosis. DNA methylation, one of the epigenetic events, plays an essential role in the carcinogenesis of many cancers, including gastric cancer. Long non-coding RNAs have emerged as the significant factors in the cancer progression functioned as the oncogene genes, the suppressor genes and regulators of signaling pathways over the decade. Intriguingly, increasing reports, recently, have claimed that abnormal DNA methylation regulates the expression of lncRNAs as tumor suppressor genes in gastric cancer and lncRNAs as regulators could exert the critical influence on tumor progression through acting on DNA methylation of other cancer-related genes. In this review, we summarized the DNA methylation-associated lncRNAs in gastric cancer which play a large impact on tumor progression, such as proliferation, invasion, metastasis and so on. Furthermore, the underlying molecular mechanism and signaling pathway might be developed as key points of gastric cancer range from diagnosis to prognosis and treatment in the future.

LncRNA as a multifunctional regulator in cancer multi-drug resistance.

BACKGROUND: Malignant tumors have become the most dangerous disease in recent years. Chemotherapy is the most effective treatment for this disease; however, the problem of drug resistance has become even more common, which leads to the poor prognosis of patients suffering from cancers. Thus, necessary measures should be taken to address these problems at the earliest. Many studies have demonstrated that drug resistance is closely related to the abnormal expressions of long non-coding RNAs (lncRNAs). METHODS AND RESULTS: This review aimed to summarize the molecular mechanisms underlying the association of lncRNAs and the development of drug resistance and to find potential strategies for the clinical diagnosis and treatment of cancer drug resistance. Studies showed that lncRNAs can regulate the expression of genes through chromatin remodeling, transcriptional regulation, and post-transcriptional processing. Furthermore, lncRNAs have been reported to be closely related to the occurrence of malignant tumors. In summary, lncRNAs have gained attention in related fields during recent years. According to previous studies, lncRNAs have a vital role in several different types of cancers owing to their multiple mechanisms of action. Different mechanisms have different functions that could result in different consequences in the same disease. CONCLUSIONS: LncRNAs closely participated in cancer drug resistance by regulating miRNA, signaling pathways, proteins, cancer stem cells, pro- and ant-apoptosis, and autophagy. lncRNAs can be used as biomarkers of the possible treatment target in chemotherapy, which could provide solutions to the problem of drug resistance in chemotherapy in the future.

Icariin-induced inhibition of SIRT6/NF-κB triggers redox mediated apoptosis and enhances anti-tumor immunity in triple-negative breast cancer.

Abnormal activation of the nuclear factor-kappa B (NF-κB) signaling pathway is closely implicated in triple-negative breast cancer growth, metastasis, and tumor immune escape. In this study, the anti-cancer effects of icariin, a natural flavonol glycoside, toward breast cancer cells and the underlying mechanisms were investigated. This investigation showed that icariin selectively inhibited proliferation and triggered apoptosis in breast cancer cells in a concentration- and time-dependent manner, but exhibited little cytotoxicity in normal breast cells. Moreover, icariin induced cell apoptosis via a mitochondria-mediated pathway, as indicated by the upregulated ratio of Bax/Bcl-2 and reactive oxygen species induction. Importantly, icariin impaired the activation of the NF-κB/EMT pathway, as evidenced by upregulation of SIRT6, resulting in inhibition of migration and invasion of breast cancer cells. Additionally, oss-128167, an inhibitor of SIRT6, dramatically attenuated anti-migration and anti-invasion effects of icariin. Transcriptomic analysis verified that impairment of NF-κB led to the selective function of icariin in breast cancer cells. Notably, icariin exhibited a significant tumor growth inhibition and anti-pulmonary metastasis effect in a tumor mouse model of MDA-MB-231 and 4T1 cells by regulating the tumor immunosuppressive microenvironment. Together, these results showed that icariin could effectively trigger apoptosis and inhibit the migration of breast cancer cells via the SIRT6/NF-κB signaling pathway, suggesting that icariin might serve as a potential candidate drug for the treatment of breast cancer.

Nifuroxazide induces apoptosis, inhibits cell migration and invasion in osteosarcoma.

Osteosarcoma is the most common primary malignancy of bone and characterized by an appendicular primary tumor with a high rate of metastasis to the lungs. Unfortunately, there is no effective strategy to treat osteosarcoma in current clinical practice. In this study, the anticancer effects and potential mechanisms of nifuroxazide, an oral nitrofuran antibiotic, on two osteosarcoma cell lines were investigated. The results of the antiproliferative activity in vitro showed that nifuroxazide inhibited cell proliferation of UMR106 and MG63 cells in a dose- and time-dependent manner. Interestingly, nifuroxazide showed low toxicity to non-tumor cells (HEK 293 T). In addition, ROS-mitochondrial mediated apoptosis was observed after treatment of nifuroxazide. Moreover, nifuroxazide could significantly inhibit osteosarcoma cells migration and invasion via p-Stat3, MMP-2 and MMP-9 mediated signaling pathway. Taken together, our results suggested that nifuroxazide could be a promising agent for osteosarcoma treatment by inhibiting cell proliferation, inducing cell apoptosis and impairing cell migration and invasion.

A Biocompatible Colorimetric Triphenylamine- Dicyanovinyl Conjugated Fluorescent Probe for Selective and Sensitive Detection of Cyanide Ion in Aqueous Media and Living Cells.

A colorimetric and turn-on fluorescent probe 1 bearing triphenylamine-thiophene and dicyanovinyl groups has been synthesized and used to detect cyanide anion via a nucleophilic addition reaction. Probe 1 exhibited prominent selectivity and sensitivity towards CN- in aqueous media, even in the presence of other anions such as S2-, HS-, SO32-, S2O32-, S2O82-, I-, Br-, Cl-, F-, NO2-, N3-, SO42-, SCN-, HCO3-, CO32- and AcO-. Moreover, a low detection limit (LOD, 51 nM) was observed. In addition, good cell membrane permeability and low cytotoxicity to HeLa cells were also observed, suggesting its promising potential in bio-imaging.

Granulosa Cells-Related MicroRNAs in Ovarian Diseases: Mechanism, Facts and Perspectives.

MicroRNAs (miRNAs) are a class of short single-stranded, noncoding RNAs that affect the translation of mRNAs by imperfectly binding to homologous 3'UTRs. Research on miRNAs in ovarian diseases is constantly expanding because miRNAs are powerful regulators of gene expression and cellular processes and are promising biomarkers. miRNA mimics, miRNA inhibitors and molecules targeting miRNAs (antimiRs) have shown promise as novel therapeutic agents in preclinical development. Granulosa cells (GCs) are supporting cells for developing oocytes in the ovary. GCs regulate female reproductive health by producing sex hormones and LH receptors. Increasing research has reported the relevance of miRNAs in GC pathophysiology. With in-depth studies of disease mechanisms, there are an increasing number of studies on the biomolecular pathways of miRNAs in gynecology and endocrinology. In the present review, we summarize the different functions of GC-related microRNAs in various ovarian disorders, such as polycystic ovary syndrome, premature ovarian insufficiency, premature ovarian failure and ovarian granulosa cell tumors.

Facts and prospects of peptide in targeted therapy and immune regulation against triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Due to the lack of specific therapeutic targets, treatment options are limited, and the recurrence and metastasis rate is high, the overall survival of patients is poor. However, with the discovery of some new targets and the corresponding immune regulation after targeting these targets, TNBC has a new hope in treatment. The peptide has a simple structure, strong binding affinity, and high stability, and has great potential in targeted therapy and immune regulation against TNBC. This review will discuss how single peptides and peptide combinations target triple-negative breast cancer to exert immunomodulatory effects. Among them, single peptides target specific receptors on TNBC cells, act as decoys to target key ligands in the regulatory pathway, and target TME-related cells. The combinations of peptides work in the form of cancer vaccines, engineered exosomes, microRNAs and other immune-related molecular pathways, immune checkpoint inhibitors, chimeric antigen receptor T cells, and drug-peptide conjugates. This article is mainly dedicated to exploring new treatment methods for TNBC to improve the curative effect and prolong the survival time of patients.

Unveiling the veil of lactate in tumor-associated macrophages: a successful strategy for immunometabolic therapy.

Lactate, traditionally regarded as a metabolic waste product at the terminal of the glycolysis process, has recently been found to have multifaceted functional roles in metabolism and beyond. A metabolic reprogramming phenomenon commonly seen in tumor cells, known as the "Warburg effect," sees high levels of aerobic glycolysis result in an excessive production of lactate. This lactate serves as a substrate that sustains not only the survival of cancer cells but also immune cells. However, it also inhibits the function of tumor-associated macrophages (TAMs), a group of innate immune cells ubiquitously present in solid tumors, thereby facilitating the immune evasion of malignant tumor cells. Characterized by their high plasticity, TAMs are generally divided into the pro-inflammatory M1 phenotype and the pro-tumour M2 phenotype. Through a process of 'education' by lactate, TAMs tend to adopt an immunosuppressive phenotype and collaborate with tumor cells to promote angiogenesis. Additionally, there is growing evidence linking metabolic reprogramming with epigenetic modifications, suggesting the participation of histone modification in diverse cellular events within the tumor microenvironment (TME). In this review, we delve into recent discoveries concerning lactate metabolism in tumors, with a particular focus on the impact of lactate on the function of TAMs. We aim to consolidate the molecular mechanisms underlying lactate-induced TAM polarization and angiogenesis and explore the lactate-mediated crosstalk between TAMs and tumor cells. Finally, we also touch upon the latest progress in immunometabolic therapies and drug delivery strategies targeting glycolysis and lactate production, offering new perspectives for future therapeutic approaches.

Dual inhibition of EGFR­VEGF: An effective approach to the treatment of advanced non­small cell lung cancer with EGFR mutation (Review).

On a global scale, the incidence and mortality rates of lung cancer are gradually increasing year by year. A number of bad habits and environmental factors are associated with lung cancer, including smoking, second­hand smoke exposure, occupational exposure, respiratory diseases and genetics. At present, low­dose spiral computed tomography is routinely the first choice in the diagnosis of lung cancer. However, pathological examination is still the gold standard for the diagnosis of lung cancer. Based on the classification and stage of the cancer, treatment options such as surgery, radiotherapy, chemotherapy, targeted therapy and immunotherapy are available. The activation of the EGFR pathway can promote the survival and proliferation of tumor cells, and the VEGF pathway can promote the formation of blood vessels, thereby promoting tumor growth. In non­small cell lung cancer (NSCLC) with EGFR mutation, EGFR activation can promote tumor growth by promoting VEGF upregulation through a hypoxia­independent mechanism. The upregulation of VEGF can make tumor cells resistant to EGFR inhibitors. In addition, the expression of the VEGF signal is also affected by other factors. Therefore, the use of a single EGFR inhibitor cannot completely inhibit the expression of the VEGF signal. In order to overcome this problem, the combination of VEGF inhibitors and EGFR inhibitors has become the method of choice. Dual inhibition can not only overcome the resistance of tumor cells to EGFR inhibitors, but also significantly increase the progression­free survival time of patients with NSCLC. The present review discusses the associations between the EGFR and VEGF pathways, and the characteristics of dual inhibition of the EGFR­VEGF pathway.

The role of peptides in reversing chemoresistance of breast cancer: current facts and future prospects.

Breast cancer is the first malignant tumor in women, and its incidence is also increasing year by year. Chemotherapy is one of the standard therapies for breast cancer, but the resistance of breast cancer cells to chemotherapy drugs is a huge challenge for the effective treatment of breast cancer. At present, in the study of reversing the drug resistance of solid tumors such as breast cancer, peptides have the advantages of high selectivity, high tissue penetration, and good biocompatibility. Some of the peptides that have been studied can overcome the resistance of tumor cells to chemotherapeutic drugs in the experiment, and effectively control the growth and metastasis of breast cancer cells. Here, we describe the mechanism of different peptides in reversing breast cancer resistance, including promoting cancer cell apoptosis; promoting non-apoptotic regulatory cell death of cancer cells; inhibiting the DNA repair mechanism of cancer cells; improving the tumor microenvironment; inhibiting drug efflux mechanism; and enhancing drug uptake. This review focuses on the different mechanisms of peptides in reversing breast cancer drug resistance, and these peptides are also expected to create clinical breakthroughs in promoting the therapeutic effect of chemotherapy drugs in breast cancer patients and improving the survival rate of patients.

Natural peptides for immunological regulation in cancer therapy: Mechanism, facts and perspectives.

Cancer incidence and mortality rates are increasing annually. Treatment with surgery, chemotherapy and radiation therapy (RT) is unsatisfactory because many patients have advanced disease at the initial diagnosis. However, the emergence of immunotherapy promises to be an effective strategy to improve the outcome of advanced tumors. Immune checkpoint antibodies, which are at the forefront of immunotherapy, have had significant success but still leave some cancer patients without benefit. For more cancer patients to benefit from immunotherapy, it is necessary to find new drugs and combination therapeutic strategies to improve the outcome of advanced cancer patients and achieve long-term tumor control or even eradication. Peptides are promising choices for tumor immunotherapy drugs because they have the advantages of low production cost, high sequence selectivity, high tissue permeability, low toxicity and low immunogenicity etc., and the adjuvant matching and technologies like nanotechnology can further optimize the effects of peptides. In this review, we present the current status and mechanisms of research on peptides targeting multiple immune cells (T cells, natural killer (NK) cells, dendritic cells (DCs), tumor-associated macrophages (TAMs), regulatory T cells (Tregs)) and immune checkpoints in tumor immunotherapy; and we summarize the current status of research on peptide-based tumor immunotherapy in combination with other therapies including RT, chemotherapy, surgery, targeted therapy, cytokine therapy, adoptive cell therapy (ACT) and cancer vaccines. Finally, we discuss the current status of peptide applications in mRNA vaccine delivery.

Unlocking the potential of Mesenchymal stem cells in liver Fibrosis: Insights into the impact of autophagy and aging.

Liver fibrosis is a chronic liver disease characterized by extracellular matrix protein accumulation, potentially leading to cirrhosis or hepatocellular carcinoma. Liver cell damage, inflammatory responses, and apoptosis due to various reasons induce liver fibrosis. Although several treatments, such as antiviral drugs and immunosuppressive therapies, are available for liver fibrosis, they only provide limited efficacy. Mesenchymal stem cells (MSCs) have become a promising therapeutic option for liver fibrosis, because they can modulate the immune response, promote liver regeneration, and inhibit the activation of hepatic stellate cells that contribute to disease development. Recent studies have suggested that the mechanisms through which MSCs gain their antifibrotic properties involve autophagy and senescence. Autophagy, a vital cellular self-degradation process, is critical for maintaining homeostasis and protecting against nutritional, metabolic, and infection-mediated stress. The therapeutic effects of MSCs depend on appropriate autophagy levels, which can improve the fibrotic process. Nonetheless, aging-related autophagic damage is associated with a decline in MSC number and function, which play a crucial role in liver fibrosis development. This review summarizes the recent advancements in the understanding of autophagy and senescence in MSC-based liver fibrosis treatment, presenting the key findings from relevant studies.

Pharmacological functions of salidroside in renal diseases: facts and perspectives.

Rhodiola rosea is a valuable functional medicinal plant widely utilized in China and other Asian countries for its anti-fatigue, anti-aging, and altitude sickness prevention properties. Salidroside, a most active constituent derived from Rhodiola rosea, exhibits potent antioxidative, hypoxia-resistant, anti-inflammatory, anticancer, and anti-aging effects that have garnered significant attention. The appreciation of the pharmacological role of salidroside has burgeoned over the last decade, making it a beneficial option for the prevention and treatment of multiple diseases, including atherosclerosis, Alzheimer's disease, Parkinson's disease, cardiovascular disease, and more. With its anti-aging and renoprotective effects, in parallel with the inhibition of oxidative stress and inflammation, salidroside holds promise as a potential therapeutic agent for kidney damage. This article provides an overview of the microinflammatory state in kidney disease and discuss the current therapeutic strategies, with a particular focus on highlighting the recent advancements in utilizing salidroside for renal disease. The potential mechanisms of action of salidroside are primarily associated with the regulation of gene and protein expression in glomerular endothelial cells, podocytes, renal tubule cells, renal mesangial cells and renal cell carcinoma cell, including TNF-α, TGF-ß, IL-1ß, IL-17A, IL-6, MCP-1, Bcl-2, VEGF, ECM protein, caspase-3, HIF-1α, BIM, as well as the modulation of AMPK/SIRT1, Nrf2/HO-1, Sirt1/PGC-1α, ROS/Src/Cav-1, Akt/GSK-3ß, TXNIP-NLRP3, ERK1/2, TGF-ß1/Smad2/3, PI3K/Akt, Wnt1/Wnt3a ß-catenin, TLR4/NF-κB, MAPK, JAK2/STAT3, SIRT1/Nrf2 pathways. To the best of our knowledge, this review is the first to comprehensively cover the protective effects of salidroside on diverse renal diseases, and suggests that salidroside has great potential to be developed as a drug for the prevention and treatment of metabolic syndrome, cardiovascular and cerebrovascular diseases and renal complications.

Role of lncRNAs in the pathogenic mechanism of human decreased ovarian reserve.

Decreased ovarian reserve (DOR) is defined as a decrease in the quality and quantity of oocytes, which reduces ovarian endocrine function and female fertility. The impaired follicular development and accelerated follicle atresia lead to a decrease in the number of follicles, while the decline of oocyte quality is related to the disorder of DNA damage-repair, oxidative stress, and the dysfunction of mitochondria. Although the mechanism of DOR is still unclear, recent studies have found that long non-coding RNA (lncRNA) as a group of functional RNA molecules participate in the regulation of ovarian function, especially in the differentiation, proliferation and apoptosis of granulosa cells in the ovary. LncRNAs participate in the occurrence of DOR by affecting follicular development and atresia, the synthesis and secretion of ovarian hormones. This review summarizes current research on lncRNAs associated with DOR and reveals the potential underlying mechanisms. The present study suggests that lncRNAs could be considered as prognostic markers and treatment targets for DOR.

Revisiting of TAMs in tumor immune microenvironment: Insight from NF-κB signaling pathway.

Tumor-associated macrophages (TAMs) are key components of tumor immune microenvironment and play a dual role in promoting tumor growth and anti-tumor immunity. Therefore, regulating TAMs has become a promising method in cancer immunotherapy. NF- κB pathway is the key regulatory pathway of TAMs. Targeting this pathway has shown the potential to improve tumor immune microenvironment. At present, there are still some controversies and the idea of combined therapy in this field. This article reviews the progress in the field of immunotherapy in improving tumor immune microenvironment by exploring the mechanism of regulating TAMs (including promoting M1 polarization, inhibiting M2 polarization and regulating TAMs infiltration).

Peptide mediated therapy in fibrosis: Mechanisms, advances and prospects.

Fibrosis, a disease characterized by an excess accumulation of extracellular matrix components, could lead to organ failure and death, and is to blame for up to 45 % of all fatalities in developed nations. These disorders all share the common trait of an unchecked and increasing accumulation of fibrotic tissue in the affected organs, which leads to their malfunction and eventual failure, even if their underlying causes are highly diverse and, in some cases, remain unclear. Numerous studies have identified activated myofibroblasts as the common cellular elements ultimately responsible for the replacement of normal tissues with nonfunctional fibrotic tissue. The transforming growth factor-ß pathway, for instance, plays a significant role in practically all kinds of fibrosis. However, there is no specific drug for the treatment of fibrosis, several medications with anti-hepatic fibrosis properties are still in the research and development stages. Peptide, which refers to a substance consisting of 2-50 amino acids, is characterized by structural diversity, low toxicity, biological activities, easy absorption, specific targeting, few side effects, and has been proven to be effective in anti-fibrosis. Here, we summarized various anti-fibrosis peptides in fibrosis including the liver, lungs, kidneys, and other organs. This review will provide a new insight into peptide mediated anti-fibrosis and is helpful to creation of antifibrotic medications.

Hierarchically tumor-activated nanoCRISPR-Cas13a facilitates efficient microRNA disruption for multi-pathway-mediated tumor suppression.

Rationale: CRISPR-Cas13a is an efficient tool for robust RNA knockdown with lower off-target effect, which may be a potentially powerful and safe tool for cancer gene therapy. However, therapeutic effect of current cancer gene therapy that targeting monogene was compromised by the multi-mutational signal pathway alterations of tumorigenesis. Methods: Here, hierarchically tumor-activated nanoCRISPR-Cas13a (CHAIN) is fabricated for multi-pathway-mediated tumor suppression by efficient microRNA disruption in vivo. A fluorinated polyetherimide (PEI; Mw=1.8KD) with graft rate of 33% (PF33) was utilized to compact the CRISPR-Cas13a megaplasmid targeting microRNA-21 (miR-21) (pCas13a-crRNA) via self-assemble to constitute a nanoscale 'core' (PF33/pCas13a-crRNA), which was further wrapped by modified hyaluronan (HA) derivatives (galactopyranoside-PEG2000-HA, GPH) to form CHAIN. Results: The dual-tumor-targeting and tumor-activated CHAIN not only manifested long-term circulation, but augmented tumor cellular uptake and endo/lysosomal escape, thus achieving efficient transfection of CRISPR-Cas13a megaplasmid (~ 13 kb) in tumor cells with minimal toxity. Efficient knockdown of miR-21 by CHAIN restored programmed cell death protein 4 (PDCD4) and reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) and further crippled downstream matrix metalloproteinases-2 (MMP-2), which undermined cancer proliferation, migration and invasion. Meanwhile, the miR-21-PDCD4-AP-1 positive feedback loop further functioned as an enhanced force for anti-tumor activity. Conclusion: Treatment with CHAIN in hepatocellular carcinoma mouse model achieved significant inhibition of miR-21 expression and rescued multi-pathway, which triggered substantial tumor growth suppression. By efficient CRISPR-Cas13a induced interference of one oncogenic microRNA, the CHAIN platform exerted promising capabilities in cancer treatment.

Baicalin triggers apoptosis, inhibits migration, and enhances anti-tumor immunity in colorectal cancer via TLR4/NF-κB signaling pathway.

Aberrant activation of the nuclear factor-kappa B (NF-κB) signaling pathway is closely implicated in colorectal cancer (CRC) growth, metastasis, and immune escape. In the present study, we reported natural derived compound of baicalin (BA), an efficient inhibitor of NF-κB, with good anti-tumor effect on CRC. CCK8 and colony formation assays showed that Baicalin significantly inhibit viability and proliferation in HCT-116 and CT26 cells. Additionally, Baicalin dramatically triggers mitochondria-mediated apoptosis in both HCT-116 and CT-26 cells, which is evidenced by loss of mitochondrial membrane potential and elevated cellular reactive oxygen species level. Treatment with Baicalin suppresses migration and invasion of CT26 cells by impairing TLR4/NF-κB signaling pathway. What's more, administration of Baicalin significantly retarded tumor growth rate in a subcutaneous xenograft tumor mouse model of CT26 cells. Treatment with Baicalin could ameliorate tumor immunosuppressive environment by downregulation of PD-L1 expression and proportion of myeloid-derived suppressor cells (MDSCs) and upregulation of percent of CD4+ and CD8+ T cells in CT26 tumors, thus improving anti-tumor immunity. In conclusion, our study demonstrated that baicalin triggers apoptosis, inhibits migration, and enhances anti-tumor immunity in colorectal cancer via TLR4/NF-κB signaling pathway, suggesting it might serve as a potential candidate drug for the treatment of CRC. PRACTICAL APPLICATIONS: In the present study, we reported natural derived compound of baicalin (BA), an efficient inhibitor of NF-κB, with good anti-tumor effect on CRC. We demonstrated that baicalin triggers mitochondria-mediated apoptosis, inhibits migration, and improves anti-tumor immunity in colorectal cancer via TLR4/NF-κB signaling pathway.