Chinese Herbal Fumigation Steam Therapy and Acupuncture in the Treatment of Knee Osteoarthritis: A Three-armed, Randomized, Controlled Trial.

Context: Knee osteoarthritis is a common form of joint disease found in humans and one of the leading causes of disability globally. Knee osteoarthritis (KOA) is responsible for a higher number of disabilities than any other medical condition affecting activities of daily living (ADL). To date no definitive, conventional medical protocol is available to deal with KOA. Objectives: The study intended to clinically investigate whether the benefits of acupuncture in the treatment of KOA) could be augmented by the addition of Chinese herbal fumigation steam therapy (CHFST) to the treatment protocol and to what degree it had benefits. Design: The research team designed a three-armed, randomized, controlled trial. The sample size was determined by analysis of power; for a sample size of 42, the power was 83.5%; the effect size was 0.5; and the α was 0.05. Setting: The setting was the traumatology department in the Chinese Medicine Branch of Taipei City Joint Hospital in Kun Ming, Taiwan. Participants: Participants were 45 males and females between the ages of 35 and 75, who were patients in the traumatology department and who were suffering from bilateral knee osteoarthritis. Three participants were lost to follow-up. Interventions: Participants were randomly assigned to one of three groups, each with 15 participants; (1) the control group, who received acupuncture only; (2) the normal CHFST group, an intervention group who received acupuncture plus a normal dose of CHFST; and (3) the one-sixteenth CHFST group, an intervention group who received acupuncture plus one-sixteenth of a normal dose of CHFST. Participants underwent biweekly treatments for four consecutive weeks. Outcomes Measures: The primary outcome measures included a visual analog scale (VAS) to assess variations in pain intensity and a goniometer measure for range of motion (ROM). Results: The addition of CHFST to acupuncture in the treatment of KOA significantly reduced pain (P = .0017) for the normal CHFST group compared to the control group and the one-sixteenth CHFST group. Chinese medical interventions overall for all groups showed a decrease in pain and increases in ROM, and health related quality of life (HrQoL). Conclusions: CHFST, in conjunction with acupuncture, showed promise in the treatment of KOA in reducing pain, increasing ROM, and improving quality of life (QoL).

Highly efficient and tumor-selective nanoparticles for dual-targeted immunogene therapy against cancer.

While immunotherapy holds great promise for combating cancer, the limited efficacy due to an immunosuppressive tumor microenvironment and systemic toxicity hinder the broader application of cancer immunotherapy. Here, we report a combinatorial immunotherapy approach that uses a highly efficient and tumor-selective gene carrier to improve anticancer efficacy and circumvent the systemic toxicity. In this study, we engineered tumor-targeted lipid-dendrimer-calcium-phosphate (TT-LDCP) nanoparticles (NPs) with thymine-functionalized dendrimers that exhibit not only enhanced gene delivery capacity but also immune adjuvant properties by activating the stimulator of interferon genes (STING)-cGAS pathway. TT-LDCP NPs delivered siRNA against immune checkpoint ligand PD-L1 and immunostimulatory IL-2-encoding plasmid DNA to hepatocellular carcinoma (HCC), increased tumoral infiltration and activation of CD8+ T cells, augmented the efficacy of cancer vaccine immunotherapy, and suppressed HCC progression. Our work presents nanotechnology-enabled dual delivery of siRNA and plasmid DNA that selectively targets and reprograms the immunosuppressive tumor microenvironment to improve cancer immunotherapy.

Identification of Substituted Naphthotriazolediones as Novel Tryptophan 2,3-Dioxygenase (TDO) Inhibitors through Structure-Based Virtual Screening.

A structure-based virtual screening strategy, comprising homology modeling, ligand-support binding site optimization, virtual screening, and structure clustering analysis, was developed and used to identify novel tryptophan 2,3-dioxygenase (TDO) inhibitors. Compound 1 (IC50 = 711 nM), selected by virtual screening, showed inhibitory activity toward TDO and was subjected to structural modifications and molecular docking studies. This resulted in the identification of a potent TDO selective inhibitor (11e, IC50 = 30 nM), making it a potential compound for further investigation as a cancer therapeutic and other TDO-related targeted therapy.

In-situ formation and assembly of gold nanoparticles by gum arabic as efficient photothermal agent for killing cancer cells.

Gold nanoparticles (AuNPs) have been established to sufficiently eradicate tumors by means of heat production for photothermal therapy. However, the translation of the AuNPs from bench to the clinic still remains to be solved until realizing high bioclearance after treatment. Herein, we developed a simple strategy for simultaneous formation and assembly of small-size gold nanoparticles (Au-SNPs) to form a novel nanocomposite in the presence of gum arabic (GA) by synchrotron X-ray irradiation in an aqueous solution within 5 min. GA, a porous polysaccharide, can not only provide a confined space in which to produce uniform Au-SNPs (1.6 ± 0.7 nm in diameter), but can also facilitate the formation of Au-SNPs@GA (diameter ≈ 40 nm) after irradiating synchrotron X-rays. Specifically, the Au-SNPs@GA possesses high thermal stability and a strong photothermal effect for killing cancer cells. Importantly, a bioclearance study demonstrated that the Au-SNPs@GA can be gradually excreted by the renal and hepatobiliary system, which might be due to the breakdown and oxidation of GA under irradiating synchrotron X-rays. Thus, the novel gold nanocomposite can be promising photothermal agents for cancer treatment at the therapeutic level, minimizing toxicity concerns regarding long-term accumulation in vivo.