The Effect of Metformin on Triple-Negative Breast Cancer Cells and Nude Mice.

Triple-negative breast cancer (TNBC) presents the most adverse prognosis due to its pronounced invasive and metastatic features. Existing research has highlighted that metformin, a prevalent diabetes medication, possesses strong anti-tumor properties, particularly in inhibiting tumor invasion and metastasis. This study delves deeper into the impact of metformin on TNBC by examining changes in proliferation, apoptosis, invasion, migration, and adhesion of TNBC cells, specifically MDA-MB-231, post-metformin exposure. The treatment of MDA-MB-231 with metformin in immunodeficient nude mice led to discernible changes in tumor metrics such as size, weight, lymph node engagement, and angiogenesis. Post-treatment, MDA-MB-231 cells exhibited a marked decline in proliferation, invasion, migration, and adhesion, alongside a significant rise in apoptosis. In the in vivo model with nude mice, tumors displayed notable reductions in size and weight post-metformin exposure. Furthermore, there was a pronounced decline in lymph node plasma cell proliferation and tumor angiogenesis. Through the use of both Enzyme-Linked Immunosorbent Assay and Real-Time Fluorescence Quantification, it was ascertained that the expression of Signal Transducer and Activator of Transcription 3 (STAT3) saw significant augmentation, while expressions of Matrix Metallopeptidase-2 (MMP-2), Matrix Metallopeptidase-9 (MMP-9), Interleukin-6 (IL-6), and Interleukin-7 (IL-7) decreased markedly. This suggests metformin's potential efficacy against TNBC, potentially mediated via the STAT3 signaling pathway and interleukins 6 and 7.

Collective Plasmon Coupling in Gold Nanoparticle Clusters for Highly Efficient Photothermal Therapy.

Plasmonic nanomaterials with strong absorption at near-infrared frequencies are promising photothermal therapy agents (PTAs). The pursuit of high photothermal conversion efficiency has been the central focus of this research field. Here, we report the development of plasmonic nanoparticle clusters (PNCs) as highly efficient PTAs and provide a semiquantitative approach for calculating their resonant frequency and absorption efficiency by combining the effective medium approximation (EMA) theory and full-wave electrodynamic simulations. Guided by the theoretical prediction, we further develop a universal strategy of space-confined seeded growth to prepare various PNCs. Under optimized growth conditions, we achieve a record photothermal conversion efficiency of up to ∼84% for gold-based PNCs, which is attributed to the collective plasmon-coupling-induced near-unity absorption efficiency. We further demonstrate the extraordinary photothermal therapy performance of the optimized PNCs in in vivo application. Our work demonstrates the high feasibility and efficacy of PNCs as nanoscale PTAs.

The RNA-binding protein GRSF1 promotes hepatocarcinogenesis via competitively binding to YY1 mRNA with miR-30e-5p.

BACKGROUND: Dysregulation of RNA binding protein (RBP) expression has been confirmed to be causally linked with tumorigenesis. The detailed biological effect and underlying mechanisms of the RBP GRSF1 in hepatocellular carcinoma (HCC) remain unclear. METHODS: HCC cells with stable knockdown of GRSF1 were established using two sh-RNA-encoding lentiviruses. The functions of GRSF1 in HCC were explored using MTT, colony formation, flow cytometry, and Transwell assays and a xenograft model. Transcriptomic sequencing in GRSF1-deficient MHCC-97H cells was carried out to identify the downstream effector of GRSF1. The regulatory mechanisms among GRSF1, YY1 and miR-30e-5p were investigated via RNA immunoprecipitation, luciferase, RNA pull-down and ChIP assays. Several in vivo assays were used to assess the selectivity of the small-molecule compound VE-821 in HCC and to confirm the absence of general toxicity in animal models. RESULTS: GRSF1 was frequently increased in HCC tissue and cells and was associated with worse clinical outcomes. GRSF1 functions as a novel oncogenic RBP by enhancing YY1 mRNA stability, and the GUUU motifs within the YY1 3`UTR 2663-2847 were the specific binding motifs for GRSF1. YY1 feedback promoted GRSF1 expression by binding to the GRSF1 promoter. In addition, YY1 was a critical target of miR-30e-5p, which was confirmed in this study to inhibit HCC hepatocarcinogenesis. GRSF1 and miR-30e-5p competitively regulated YY1 by binding to its 3`UTR 2663-2847 region. Finally, we identified that VE-821 blocked HCC progression by inhibiting the GRSF1/YY1 pathway. CONCLUSION: This study revealed the interaction network among GRSF1, YY1 and miR-30e-5p, providing new insight into HCC pathogenesis, and indicated that VE821 may serve as a novel agent with potential for HCC treatment through inhibition of the GRSF1/YY1 axis.

Three-dimensional crossbar arrays of self-rectifying Si/SiO2/Si memristors.

Memristors are promising building blocks for the next-generation memory and neuromorphic computing systems. Most memristors use materials that are incompatible with the silicon dominant complementary metal-oxide-semiconductor technology, and require external selectors in order for large memristor arrays to function properly. Here we demonstrate a fully foundry-compatible, all-silicon-based and self-rectifying memristor that negates the need for external selectors in large arrays. With a p-Si/SiO2/n-Si structure, our memristor exhibits repeatable unipolar resistance switching behaviour (105 rectifying ratio, 104 ON/OFF) and excellent retention at 300 °C. We further build three-dimensinal crossbar arrays (up to five layers of 100 nm memristors) using fluid-supported silicon membranes, and experimentally confirm the successful suppression of both intra- and inter-layer sneak path currents through the built-in diodes. The current work opens up opportunities for low-cost mass production of three-dimensional memristor arrays on large silicon and flexible substrates without increasing circuit complexity.

Effect of acupuncture on Deqi traits and pain intensity in primary dysmenorrhea: analysis of data from a larger randomized controlled trial.

BACKGROUND: Deqi is a central concept in traditional Chinese acupuncture. We performed a secondary analysis on data from a larger randomized controlled trial (RCT) in order to assess the effect of acupuncture on deqi traits and pain intensity in primary dysmenorrhea. METHODS: A total of 60 primary dysmenorrhea patients were enrolled and randomly assigned to one of three treatment groups. Acupuncture was given at SP6, GB39 or nonacupoint. Subjective pain was measured by a 100-mm visual analogue scale (VAS) before and after acupuncture. The Massachusetts General Hospital acupuncture sensation scales (MASS) with minor modification was used to rate deqi sensations during acupuncture. RESULTS: The results showed that VAS scores of pain after acupuncture were significantly decreased comparing to before acupuncture treatment in all three groups (P = 0.000). However, no significant differences were found among three groups at the beginning or end of acupuncture treatment (P = 0.928, P = 0.419). CONCLUSIONS: There was no statistical difference among three groups in terms of intensity of deqi feeling. The types of sensation were similar across the groups with only minor differences among them. TRIAL REGISTRATION NUMBER: Controlled-Trials.com ISRCTN24863192.

Effects of deqi on autonomic balance in adult tinnitus patients: study design of a randomized controlled trial.

Background. Recent reports suggest that a proportion of tinnitus patients suffer from mental illness. Autonomic nervous system plays a useful role in tinnitus therapy since electrical vagal nerve stimulation (VNS) has been frequently used to alleviate tinnitus-induced depression in clinic. heart rate variability (HRV), which is reflective of autonomic nervous system function, has been proved to be modulated by acupuncture. In the present study, we aim to compare the effect of deqi sensation on heart rate variability in adult tinnitus patients. Methods. Thirty participants are randomly assigned to verum acupuncture (creating deqi) or shallow acupuncture (not creating deqi) at Baihui (Du-20), Shenting (Du-24), Tinghui (GB-2), Waiguan (SJ-5), and Zulinqi (GB-41) for 3 weeks. The primary outcome measure is heart rate variability, which is measured at the first acupuncture, as well as the last acupuncture. Discussion. Completion of this trial will help to identify the role of deqi sensation in acupuncture effect for tinnitus and reveal an autonomic modulation mechanism for acupuncture effect. Trial Registration. This trial is registered with International Standard Randomised Controlled Trial Number ISRCTN58013563.

Acupuncture at local and distant points for tinnitus: study protocol for a randomized controlled trial.

BACKGROUND: Tinnitus is the perception of a sound in the absence of an objective physical source. Up to now, there is no generally accepted view how these phantom sounds come about, and also no efficient treatment. Patients are turning to complementary or alternative medical therapies, such as acupuncture. Based on the theory of traditional Chinese medicine, acupoints located on both the adjacent and distal area of the disease can be needled to treat disease. Furthermore, the way of combining acupoints is for strengthening the curative effect. We aim to evaluate the efficacy of acupuncture at local points in combination with distal points in subjective tinnitus patients. METHOD: This trial is a randomized, single-blind, controlled study. A total of 112 participants will be randomly assigned to one of four treatment groups receiving acupuncture treatment for 4 weeks. The primary outcome measure is subjective tinnitus loudness and annoyance perception, which is graded using the Visual Analogue Scale (VAS). The assessment is at baseline (before treatment initiation), 4 weeks after the first acupuncture session, and 8 weeks after the first acupuncture session. DISCUSSION: Completion of this trial will help to identify whether acupuncture at local acupoints in combination with distal acupoints may be more effective than needling points separately. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number Register: ISRCTN29230777.

[The study of anti-tumor effect of Tetrandrine combined with Nedaplatin on human liver cancer cell line 7402].

OBJECTIVE: To study the anti-tumor effect of Tetrandrine (Tet) combined with Nedaplatin (Nap) on the human liver cancer cell line 7402, and explore its mechanism. METHODS: Human liver cancer line 7402 was treated by Tet and Nap in various concentrations respectively or in combination in vitro,and then the cell growth was assayed by MTT method, periodic return changes were observed by aridine orange (AO)-/ethidiumbromide (EB) fluorescent staining, DNA gel eledtophoresis and flow cytometry, and the expression of apoptosis-related genes were analyzed by immunohistochemical staining method. RESULTS: Compared with Tet or Nap individual drug groups, Tet combined with Nap obviously increased the inhibitatory rate and apoptosis rate of the human liver cancer cell line 7402. The cell cycle distribution was altered and ratio of S phase and G2/M phase cell increased following the treatment with Tet combined with Nap, with Bcl-2 gene expression down-regulated, and BAX gene expression up-regulated. CONCLUSION: Tet combined with Nap can obviously increase apoptosis-inducing effect, and its mechanism may be regulating cell cycle and increasing apoptosis-inducing effect which is regulated by several genes.