Inhibited Tumor Cell Proliferation Research Articles

Ursolic acid in colorectal cancer: mechanisms, current status, challenges, and future research directions.

Colorectal cancer (CRC) ranks as the third most prevalent cancer globally, contributing to approximately 10% of all cancer cases and representing the second leading cause of cancer-related mortality worldwide. Ursolic acid (UA), a widely studied pentacyclic triterpenoid, has attracted substantial attention from researchers and clinicians due to its potential therapeutic effects against malignant tumors. Multiple studies have confirmed that UA inhibits tumor cell proliferation, induces differentiation and apoptosis, suppresses invasion, and impedes tumor angiogenesis via diverse mechanisms. However, research specifically addressing UA's anti-CRC effects remains limited, and systematic reviews of its underlying mechanisms in CRC are scarce. This study seeks to provide a comprehensive review of UA's mechanisms of action against CRC, offering valuable insights and references for researchers and clinicians.

Correlation of NAT10 expression with clinical data and survival profiles in esophageal squamous cell carcinoma patients, and its impact on cell proliferation and apoptosis.

This study investigates the association between NAT10 expression and clinical parameters while assessing prognostic outcomes in esophageal squamous cell carcinoma (ESCC) patients. Furthermore, the study seeks to elucidate the functional role of NAT10 in neoplastic cell proliferation and apoptosis. NAT10 expression was assessed in ESCC tissue microarrays through immunohistochemistry (IHC) tests. We employed SPSS software to analyze the correlation between NAT10 staining data, clinical indicators, and their implications for patient prognosis. Small interference RNA (siRNA) was utilized to inhibit NAT10 expression in two esophageal cancer cell lines, TE-1 and KYSE150. Subsequently, we meticulously quantified and compared cellular proliferation and apoptotic ratios among experimental groups. NAT10, Ki67, and Caspase3 expression levels in different groups were evaluated using quantitative polymerase chain reaction (qPCR) and Western blot (WB) assays. Statistical analyses were conducted using GraphPad Prism software, with significance at P<0.05. Our findings indicate that NAT10 is overexpressed in ESCC tissues and exhibits a significant correlation with tumor diameter and overall patient survival. Decreasing NAT10 expression led to the inhibition of tumor cell proliferation and the promotion of apoptosis. Furthermore, siRNA-mediated NAT10 inhibition resulted in the downregulation of Ki67 expression and the concomitant upregulation of Caspase3. The observed overexpression of NAT10 in ESCC tissues is associated with larger tumor diameters and reduced patient survival. NAT10 appears to play a pivotal role in the progression of esophageal cancer by influencing cell proliferation and apoptosis. These findings suggest potential clinical implications, with Ki67 and Caspase3 potentially participating in this intricate molecular biological process.

Nicotinamide mononucleotide protects STAT1 from oxidative stress-induced degradation to prevent colorectal tumorigenesis.

Colitis, accompanied by the accumulation of reactive oxygen species (ROS) in the intestinal tract, is a risk factor for colorectal cancer (CRC). Our previous studies indicate that nicotinamide mononucleotide (NMN) replenishment reduces chronic inflammation. In this study, we confirm that NMN supplementation reduces inflammatory cytokine levels and oxidative tissue damage in an azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated cancer (CAC) model. Mice treated with NMN developed fewer colon tumors than untreated animals under the same AOM/DSS treatment conditions. Quantitative proteomic analysis revealed a decrease in signal transducer and activator of transcription 1 (STAT1) expression in the CAC model. We demonstrate that STAT1 overexpression induces G1 arrest by downregulating CDK6 expression and suppressing tumor cell proliferation and migration. Of note, H2O2 induced trioxidation of the STAT1 protein and promoted its degradation, which was partially reversed by NMN supplementation. Upon H2O2 treatment, Cys155 in STAT1 was oxidized to sulfonic acid, whereas the mutation of Cys155 to alanine abolished ROS-mediated STAT1 degradation. These results indicate that oxidative stress induces STAT1 degradation in tumor cells and possibly in CAC tissues, whereas supplementation with NMN protects STAT1 from oxidation-induced degradation and prevents tumorigenesis. This study provides experimental evidence for the development of NMN-mediated chemoprevention strategies for CRC.

Polyphyllin VI: A promising treatment for prostate cancer bone metastasis

Prostate cancer, as one of the most prevalent malignant tumors in men, seriously affects the prognosis and survival of patients due to its extremely high rate of bone metastasis. This study investigated the effect of Polyphyllin VI (PPVI) on metastatic bone disease for the first time in prostate cancer, focusing on its impact on osteoclast and tumor cell. In vitro studies utilized TRAP staining, ghost pen cyclic peptide staining, and bone resorption assays to evaluate the differentiation and function of receptor activator of nuclear factor-κB ligand (RANKL) induced and RM-1 conditional medium (CM) induced osteoclasts. The colony formation assay, wound healing assay, and Transwell assay were employed to analyze tumor cell proliferation, migration, and invasion in vitro. Flow cytometry was used to detect the cycling and apoptosis of tumor cells in vitro. Western Blot and PCR assays were conducted to assess the expression of genes. In vivo, micro-CT, hematoxylin-eosin staining, and immunohistochemical staining evaluated the impact of PPVI on bone destruction and tumor growth in a mouse model of tumor tibial metastasis. The study results indicated that PPVI effectively inhibited osteoclast differentiation, suppresses tumor cell proliferation, migration, and invasion in vitro, and induces apoptosis and G2/M phase arrest. In vivo, PPVI not only inhibits the growth of metastatic tumors but also mitigates the resulting bone destruction. These results suggest that PPVI holds significant potential as an alternative treatment for prostate cancer with bone metastasis, providing insights into its molecular mechanisms and therapeutic efficacy.

Validation of the biological function and prognostic significance of AURKA in neuroblastoma.

Neuroblastoma (NB) is the most common extracranial solid tumor in children, and the AURKA gene encodes a protein kinase involved in cell cycle regulation that plays an oncogenic role in a variety of human cancers. The aim of this study was to validate the biological function and prognostic significance of AURKA in NB using basic experiments and bioinformatics. Data obtained from Target and GEO databases were analyzed using various bioinformatic techniques. The expression of AURKA in 77 NB samples was detected by immunohistochemistry (IHC) method. The lentiviral RNA interference technique was employed to downregulate AURKA gene expression in NB cell lines. Additionally, cell counting kit-8 and flow cytometry analysis were conducted to investigate the impact of AURKA expression on cell proliferation, cell cycle progression, and apoptosis. A bioinformatic analysis showed that patients with NB in the AURKA-high-expression group had shorter OS (Overall Survival). Immune cell infiltration analysis showed that only activated CD4 T cell and type 2 T helper cell infiltration levels were higher in the AURKA-high-expression group than in the AURKA-low-expression group, with the infiltration levels of most other immune cells and cytokines lower in the high-expression group. Furthermore, the enhanced infiltration of activated CD4 T cells was associated with worse OS in patients with NB. IHC results showed that the AURKA expression was correlated with MYCN status and INSS stage. Log-rank test showed that pathological type, MYCN status, INSS stage, COG risk group, and AURKA expression was related to PFS (Progression-free survival) of NB patients, but COX regression analysis showed that none of the above factors were independently prognostic for PFS. In vitro, shRNA delivered via an AURKA-specific lentivirus significantly and consistently silenced endogenous AURKA expression in the human NB cell line SK-N-AS. This inhibited tumor cell proliferation, induced apoptosis, and caused G2/M-phase cell cycle arrest. Moreover, western blot assay showed significant reductions in the levels of mTOR, p70S6K, and 4E-BP1 phosphorylation in the AURKA-knockdown group. I found in subsequent experiments that NFYB can bind to the AURKA promoter and thus promote AURKA expression. High-level AURKA expression in NB is associated with poor patient prognosis. Silencing AURKA inhibited tumor cell proliferation, induced tumor cell apoptosis, and led to cell cycle arrest in the G2/M phase. Mechanistically, AURKA knockdown inhibited the phosphorylation and the activation of the mTOR1/p70S6K/4E-BP1 signaling pathway. In addition, AURKA was observed to regulate the infiltration levels of various immune cells in the NB tumor microenvironment, resulting in remodeling of the immunosuppressive tumor microenvironment.

Scutellaria baicalensis and its flavonoids in the treatment of digestive system tumors

Scutellaria baicalensis has been used for the treatment of digestive system disorders for thousands of years in China and other regions. Modern research have revealed its therapeutic efforts in digestive system tumors. Thus, to review the updated progress of S. baicalensis and its main flavonoids in the treatment of digestive system tumors in the past 10 years, this article summarized the therapeutic effect and molecular mechanisms of S. baicalensis and its 5 flavonoids on tumors in oral cavity, esophagus, stomach, colon, liver, pancreas by inhibiting tumor cell proliferation, inducing autophagy, stimulating immune response, and increasing drug sensitivity. In conclusion, S. baicalensis and its flavonoids could be applied to treat digestive system tumors with different type of methods.

Additively Manufactured Biodegradable Zn-Based Porous Scaffolds to Suppress Osteosarcoma and Promote Osteogenesis.

Postoperative therapies for osteosarcoma present substantial challenges due to tumor recurrence and extensive bone defects. To tackle these challenges, laser powder bed fusion is utilized to fabricate biodegradable Zn-Li porous scaffolds that supress tumors and promote osteogenesis. After the structure design and composition selection, the Zn-0.8Li porous scaffold with Gyroid unit optimally balances the co-release of Zn2+ and Li+ during degradation, resulting in favorable antitumor and osteogenic effects. In vitro, the Zn-0.8Li scaffold significantly inhibits osteosarcoma progression by suppressing tumor cell proliferation, promoting apoptosis, alleviating migration, and simultaneously promotes osteogenic differentiation through the enhanced expression of osteogenic markers. In vivo, the Zn-0.8Li scaffold inhibits the malignant osteosarcoma behavior and facilitates bone regeneration in areas with bone defects. Transcriptomic analysis further reveals that the simultaneous release of Zn2+ and Li+ from the biodegradable Zn-0.8Li scaffold contributes to anti-osteosarcoma activity by downregulating PI3K/Akt signaling pathways. Taken together, the Zn-0.8Li porous scaffold fabricated using laser powder bed fusion with enhanced antitumor and osteogenic properties is a promising alternative for the postoperative management of osteosarcoma.

Antitumor effects and molecular mechanisms of matrine

Abstract. Matrine possesses various pharmacological activities such as anti-fibrosis, antiviral, anti-inflammatory, and immunosuppressive effects, especially playing a crucial role in antitumor activities. Studies have shown that matrine exerts antitumor effects through multiple pathways, including inhibiting tumor cell proliferation and metastasis, inducing tumor cell apoptosis, and suppressing tumor angiogenesis. This paper reviews the recent research progress on the antitumor effects and molecular mechanisms of matrine, aiming to provide theoretical references for its further research and application.

Population Pharmacokinetics of Tamibarotene in Pediatric and Young Adult Patients with Recurrent or Refractory Solid Tumors.

Tamibarotene is a synthetic retinoid that inhibits tumor cell proliferation and promotes differentiation. We previously reported on the safety and tolerability of tamibarotene in patients with recurrent or refractory solid tumors. Therefore, in this study, we aimed to evaluate the pharmacokinetic properties of tamibarotene and construct a precise pharmacokinetic model. We also conducted a non-compartmental analysis and population pharmacokinetic (popPK) analysis based on the results of a phase I study. Targeted pediatric and young adult patients with recurrent or refractory solid tumors were administered tamibarotene at doses of 4, 6, 8, 10, and 12 g/m2/day. Serum tamibarotene concentrations were evaluated after administration, and a popPK model was constructed for tamibarotene using Phoenix NLME. During model construction, we considered the influence of various parameters (weight, height, body surface area, and age) as covariates. Notably, 22 participants were included in this study, and 109 samples were analyzed. A two-compartment model incorporating lag time was selected as the base model. In the final model, the body surface area was included as a covariate for apparent total body clearance, the central compartment volume of distribution, and the peripheral compartment volume of distribution. Visual prediction checks and bootstrap analysis confirmed the validity and predictive accuracy of the final model as satisfactory.

Mechanistic insights into traditional Chinese medicine for digestive tract cancers: implications for gastric, hepatic, esophageal, intestinal, and pancreatic tumors

Abstract The increasing incidence of cancer-related deaths highlights the pressing need for effective treatment modalities, particularly in the context of digestive tract cancers, such as gastric, hepatic, esophageal, intestinal, and pancreatic tumors. While conventional drug therapies play a critical role in managing these malignancies, their associated side effects often pose significant challenges to patient quality of life. Thus, there is a growing focus on traditional Chinese medicine (TCM) and its compounds, which are safe, non-toxic, and reliable. During anti-tumor therapy, TCM compounds, based on their multi-target, multi-pathway, and multi-level regulatory effects, fully mobilize multiple mechanisms of the body, presenting significant advantages in inhibiting tumor development, boosting patient welfare, and increasing their lifespan. This article reviews the mechanisms by which TCM inhibits tumor cell proliferation, promotes tumor cell death, suppresses tumor cell invasion and metastasis, regulates the tumor microenvironment, inhibits angiogenesis, and enhances anti-tumor drug resistance. This knowledge might provide a theoretical and scientific basis for preventing and treating tumors using TCM.

DDDR-03. DEVELOPMENT OF ANTI-TUMOR AROMA THERAPY FOR GLIOBLASTOMA WITH LEMONGRASS ESSENTIAL OIL

Abstract INTRODUCTION Aroma essential oils apply to cancer therapy because of their immune-enhancing and sedative effects, and their ability to reduce the side effects of chemotherapy. Recently, aroma essential oils have also been reported to have anti-tumor effects. We investigate the anti-tumor effects of aromatic compounds contained in essential oils as a novel treatment for glioblastoma. In this study, we analyzed the antitumor effect of lemongrass essential oil and investigated its antitumor aroma therapy for glioblastoma. methods and RESULTS Human glioblastoma cells (U87, T98G) and mouse brain tumor cells (RSV-M) were used in the study. Tumor cells were cultured in the presence of lemongrass essential oil for 72 hours, and the growth inhibitory effect was observed, suggesting that the evaporated lemongrass essential oil components acted on tumor cells in the vicinity. In addition, a similar effect was observed with citral alone, which is the main component of lemongrass. Analysis of the effects of citral revealed that citral strongly binds to MARK4 and inhibits its enzyme activity, and that citral decreases the phosphorylation of tau protein. Next, a mouse brain tumor model with RSV-M was established, and the anti-tumor effect of lemongrass essential oil was studied. The results showed that the mice that inhaled lemongrass essential oil for 12 h/day had a significantly prolonged survival period compared to the control group. DISCUSSION Citral is the main component of lemongrass essential oil, which contains 70-80% of lemongrass essential oil. This study suggests a mechanism of inhibition of tumor cell proliferation by citral in malignant gliomas. Citral is a volatile monoterpene, and its anti-tumor effect was demonstrated by diffusion through evaporation. CONCLUSION Citral in lemongrass essential oil shows anti-tumor effects and is expected to be applied to a new glioblastoma therapy using “aroma”

Living photosynthetic microneedle patches for in situ oxygenation and postsurgical melanoma therapy

Surgical excision remains the principal treatment for melanoma, while tumor recurrence and delayed wound healing often occur due to the residual tumor cells and hypoxic microenvironment in the postoperative skin wounds. Herein, we present a living photosynthetic microneedle (MN) patch (namely MA/CM@MN) loaded with microalgae (MA) and cuttlefish melanin (CM) for postsurgical melanoma therapy and skin wound healing. Benefiting from the oxygenic photosynthesis of the alive MA in the MN base, the MA/CM@MN can generate oxygen under light exposure, thus facilitating skin cell proliferation and protecting cells against hypoxia-induced cell death. In addition, with CM nanoparticles embedded in the MN tips, the MA/CM@MN can be effectively heated up under near-infrared (NIR) irradiation, contributing to a strong tumor killing efficacy on melanoma cells in vitro. Further experiments demonstrate that the NIR-irradiated MA/CM@MN effectively prevents local tumor recurrence and simultaneously promotes the healing of tumor-induced wounds after incomplete tumor resection in melanoma-bearing mice, probably because the MA/CM@MN can inhibit tumor cell proliferation, stimulate tumor cell apoptosis, and mitigate tissue hypoxia in light. These results indicate that the living photosynthetic MN patch offers an effective therapeutic strategy for postoperative cancer therapy and wound healing applications.Graphical

DDDR-47. TARGETING HTR2B SUPPRESSES NON-FUNCTIONING PITUITARY ADENOMA GROWTH AND SENSITIZES CABERGOLINE TREATMENT VIAINHIBITING GΑQ/PLC/PKCΓ/STAT3 AXIS

Abstract BACKGROUND Managing non-functioning pituitary adenomas (NFPAs) is difficult due to limited drug treatments. Cabergoline’s (CAB) effectiveness for NFPAs is debated. This study explores the role of HTR2B in NFPAs and its therapeutic potential. METHODS We conducted screening of bulk RNA-sequencing data to analyze HTR2B expression levels in NFPA samples. In vitro and in vivo experiments were performed to evaluate the effects of HTR2B modulation on tumor growth and cell cycle regulation. Mechanistic insights into the HTR2B-mediated signaling pathway were elucidated using pharmacological inhibitors and molecular interaction assays. RESULTS Elevated HTR2B expression was detected in NFPA samples, which was associated with increased tumor survival. Inhibition of HTR2B activity resulted in the suppression of tumor growth through modulation of the G2M cell cycle. The inhibition of HTR2B with PRX-08066 was found to block STAT3 phosphorylation and nuclear translocation by interfering with the Gαq/PLC/PKC pathway. A direct interaction between PKC-γ and STAT3 was critical for STAT3 activation. CAB was shown to activate pSTAT3 via HTR2B, reducing its therapeutic potential. However, the combination of an HTR2B antagonist with CAB significantly inhibited tumor cell proliferation in HTR2B-expressing pituitary tumor cell lines, a xenografted pituitary tumor model, and patient-derived samples. Analysis of patient-derived data indicated that a distinct molecular pattern characterized by upregulated HTR2B/PKC-γ and downregulated BTG2/GADD45A may benefit from combination treatment with CAB and PRX-08066.

Desuccinylation of inosine-5′-monophosphate dehydrogenase 1 by SIRT5 promotes tumor cell proliferation

Inosine-5´-monophosphate dehydrogenase (IMPDH) catalyzes the rate limiting step of de novo purine synthesis. Currently, it remains still largely unknown how this metabolic event is regulated in tumor cells. Here, we report that a deacetylase sirtuin 5 (SIRT5) may possess a regulatory effect on GMP anabolism by desuccinylating IMPDH1. We found that SIRT5 can directly interacts with IMPDH1 and promotes desuccinylation on the N terminal of IMPDH1, thereby leading to increased IMPDH enzymatic activity, enhanced purine biosynthesis and promoted cell proliferation. Consistently, down-regulation of SIRT5 expression results in decreased IMPDH1 activity and impaired tumor cell proliferation. Therefore, our results reveal that SIRT5-mediated IMPDH1 desuccinylation adapts purine metabolism for rapid cell growth, and could be a potential therapeutic target for tumor cell proliferation inhibition.

Dysregulation of R-loop homeostasis shapes the immunosuppressive microenvironment and induces malignant progression in melanoma.

Dysregulated R-loop homeostasis leads to DNA replication stress and genomic instability, a major driver of cancer. However, the role of R-loops in melanoma development remains unclear. We established an R-loop scoring model based on a single-cell RNA sequencing dataset and evaluated the association between the R-loop score with the melanoma immune microenvironment and treatment response. We explored the role of CENPA-mediated changes in R-loop distribution during melanoma progression by DNA/RNA immunoprecipitation and sequencing and a series of functional experiments. We found that malignant cells with high R-loop scores may be involved in melanoma progression by modulating immune evasion, metabolic reprogramming, and cancer-related pathways. A cell communication analysis revealed that high-score R-loops play an important role in altering cell-cell interactions and limiting the CD8 + cytotoxic T cell response and T cell accumulation. CENPA silencing induced changes in R-loop distribution, upregulated Hippo signaling activity, and inhibited tumor cell proliferation and migration. Moreover, the R-loop score can predict the prognosis and immunotherapy effect of melanoma patients. Our work reveals the potential molecular mechanism by which abnormal R-loops promote melanoma progression, which may help develop anticancer therapies based on R-loops or R-loop regulators.

Deciphering the oncogenic potential of ADAM9 in hepatocellular carcinoma through bioinformatics and experimental approaches

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. This study investigates the role and mechanisms of ADAM9 as a biomarker and potential therapeutic target in HCC. Utilizing RNA-sequencing data and clinicopathological characteristics from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we conducted survival and meta-analyses, functional enrichment, and immune infiltration studies. Additionally, we evaluated the effects of ADAM9 silencing on HCC cell proliferation, migration, and invasion through in vitro experiments. Our results demonstrate that high ADAM9 expression is associated with poor prognosis and increased immune infiltration in HCC patients. Furthermore, ADAM9 knockdown significantly inhibited tumor cell proliferation and migration. These findings indicate that ADAM9 is a promising prognostic biomarker and potential therapeutic target in HCC. In conclusion, ADAM9 could offer avenues for developing strategies to inhibit tumor progression and improve patient outcomes.

The acetylglucosaminyltransferase GnT-Ⅲ regulates erythroid differentiation through ERK/MAPK signaling

Differentiation therapy is an alternative strategy used in treating chronic myelogenous leukemia (CML) to induce the differentiation of immature or cancerous cells towards mature cells and inhibit tumor cell proliferation. We aimed to explore N-glycans' roles in erythroid differentiation using the sodium butyrate (NaBu)-induced model of K562 cells (WT/NaBu cells). Here, using lectin blot, flow cytometry, real-time PCR, and mass spectrometry analyses, we demonstrated that the mRNA levels of N-acetylglucosaminyltransferase Ⅲ (GnT-Ⅲ encoded by the MGAT3 gene) and its product (bisected N-glycans) were significantly increased during erythroid differentiation. To address the importance of GnT-Ⅲ in this progress, we established a stable MGAT3 knockout (KO) K562 cell line using the CRISPR/Cas9 technology. Compared to WT/NaBu cells, MGAT3 KO significantly impeded the progression of erythroid differentiation, as shown in decreased cell color and levels of erythroid markers, glycophorin A (CD235a), and β-globin. Consistently, MGAT3 KO mitigated the inhibitory impact of NaBu on cell proliferation. During induction, MGAT3 KO suppressed the cellular phosphorylated tyrosine and phospho-ERK1/2 levels. Inhibition of the ERK/MAPK signaling pathway using U0126 blocked erythroid differentiation while concurrently suppressing the expression levels of MGAT3 and bisected N-glycans. Furthermore, the lack of bisecting GlcNAc modification on c-Kit and transferrin receptor 1 (CD71) suppressed cellular signaling and accelerated the degradation of the CD71 protein, respectively. Our study highlights the critical role of MGAT3 in regulating erythroid differentiation associated with the ERK/MAPK signaling pathway, which may shed light on identifying new differentiation therapy in chronic myelogenous leukemia.

SERPING1 Reduces Cell Migration via ERK-MMP2-MMP-9 Cascade in Sorafenib- Resistant Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignant tumor, and it ranks 2nd in terms of mortality rate among all malignancies in Taiwan. Sorafenib is a multiple tyrosine kinase inhibitor that suppresses tumor cell proliferation and angiogenesis around tumors via different pathways. However, the survival outcome of advanced HCC patients treated with sorafenib is still unsatisfactory. Unfortunately, there are no clinically applicable biomarkers to predict sorafenib therapeutic efficiency in HCC thus far. We found that serpin peptidase inhibitor, clade G, member 1 (SERPING1) is highly associated with overall and recurrence-free survival rates in HCC patients and is also highly correlated with several clinical parameters. SERPING1 expression was increased with sorafenib in both the HCC cell extract and conditioned medium, which was also observed in sorafenib-resistant HepG2 and Huh7 cells. Sorafenib decreased cell viability and migration, which was similar to the effect of SERPING1 in HCC progression. Moreover, sorafenib inhibited both MMP-2 and MMP-9 activity and enhanced the expression of p-ERK in HCC cells. In summary, sorafenib reduces HCC cancer progression might through the p-ERK-MMP-2-MMP-9 cascade via upregulation of SERPING1. In the present study, the roles and molecular mechanisms of SERPING1 and its value as a marker for predicting sorafenib resistance and progression in HCC patients were examined. The results of the present study provide a deep understanding of the roles of SERPING1 in HCC sorafenib resistance, which can be applied to develop early diagnosis and prognosis evaluation methods and establish novel therapeutic targets for specifically treating HCC.

Human decidua basalis mesenchymal stem/stromal cells enhance anticancer properties of human natural killer cells, in vitro.

Mesenchymal stem cells/stromal cells from the Decidua Basalis of the human placenta (DBMSCs) express wide range of effector molecules that modulate the functions of their target cells. These properties make them potential candidate for use in cellular therapy. In this study, we have investigated the consequences of interaction between DBMSCs and natural killer (NK) cells for both cell types. DBMSCs were cultured with IL-2-activated and resting non-activated NK cells isolated from healthy human peripheral blood and various functional assays were performed including, NK cell proliferation and cytolytic activities. Flow cytometry and microscopic studies were performed to examine the expression of NK cell receptors that mediate these cytolytic activities against DBMSCs. Moreover, the mechanism underlying these effects was also investigated. Our findings revealed that, co-culture of DBMSCs and NK cells resulted in inhibition of proliferation of resting NK cells, while proliferation of IL-2 activated NK cells was increased. Contrarily, treatment of DBMSC's with comparatively high numbers of IL-2 activated NK cells, resulted in their lysis, whereas treatment with low numbers resulted in reduction in their proliferation. Cytolytic activity of NK cells against DBMSCs was mediated by several activating NK cell receptors. In spite of the expression of HLA class I molecules by DBMSCs, they were still lysed by NK cells, excluding their involvement in cytolytic activity. In addition, preconditioning NK cells by DBMSCs, enhanced their ability to suppress tumor cell proliferation and in severe cases resulted in their partial lysis. Lysis and decrease of tumor cell proliferation is associated with increased expression of important molecules involved in anticancer activities. We conclude that DBMSCs exhibit dualfunctions on NK cells that enhance their anticancer therapeutic potential.

Terahertz spectroscopy study of oridonin and ponicidin in the anticancer Chinese herbal medicine Rabdosia rubescens.

Rabdosia rubescens, a Chinese herbal medicine with anticancer properties, contains two active ingredients: oridonin and ponicidin. Both compounds exhibit antitumor effects by inducing tumor cell apoptosis and autophagy and inhibiting tumor cell proliferation. To further explore the differences in molecular structure and pharmacological properties between the two substances, this study employs Terahertz Time-Domain Spectroscopy (THz-TDS) to investigate the spectral characteristics of oridonin and ponicidin in the frequency range of 0.1 to 2.3 THz. The crystal structures of the two substances are simulated using Materials Studio software and Density Functional Theory (DFT), yielding their spectra and molecular vibration modes, which elucidate the mechanism underlying the peak generation. The consistency between experimental and simulation results confirms the reliability of the experimental findings. Thus, THz spectroscopy can effectively distinguish between these two substances. Finally, a THz detection is performed on Rabdosia rubescens capsules purchased from the market, revealing the presence of absorption peaks for both substances in their absorption spectra. This provides a new approach for detecting active ingredients in Chinese herbal medicines.