Fluorocarbon Modified Chitosan to Enable Transdermal Immunotherapy for Melanoma Treatment.

Despite the rapid development of the immune checkpoint blockade (ICB) in melanoma treatment, the immunosuppressive tumor microenvironment (TME) still hinders the efficacy of immunotherapy. Recently, using agonists to modulate the TME have presented promising clinical responses in combination with ICB therapies. However, local intratumoral injection as the commonly used administration route for immune agonists would lead to low patient compliance. Herein, it is demonstrated that fluorocarbon modified chitosan (FCS) can self-assemble with immune adjuvant polyriboinosinic:polyribocytidylic acid (poly(I:C)), forming nanoparticles that can penetrate through cutaneous barriers to enable transdermal delivery. FCS/poly(I:C) can efficiently activate various types of cells presented on the transdermal route (through the skin into the TME), leading to IRF3-mediated IFN-ß induction in the activated cells for tumor repression. Furthermore, transdermal FCS/poly(I:C) treatment can significantly magnify the efficacy of the programmed cell death protein 1 (PD-1) blockade in melanoma treatment through activating the immunosuppressive TME. This study approach offered an attractive transdermal approach in combined with ICB therapy for combined immunotherapy, particularly suitable for melanoma treatment.

Turning Waste into Wealth: A Potent Sono-Immune Strategy Based on Microcystis.

Currently, sonodynamic therapy (SDT) has limited therapeutic outcomes and immune responses, highlighting the urgent need for enhanced strategies that can stimulate robust and long-lasting antitumor effects. Microcystis, a notorious microalga, reveals the possibility of mediating SDT owing to the presence of gas vesicles (GVs) and phycocyanin (PC). Herein, a nontoxic strain of Microcystis elabens (labeled Me) is developed as a novel agent for SDT because it generates O2 under red light (RL) illumination, while GVs and PC act as cavitation nuclei and sonosensitizers, respectively. Moreover, algal debris is released after ultrasound (US) irradiation, which primes the Toll-like receptor pathway to initiate a cascade of immune responses. This sono-immune strategy inhibits CT26 colon tumor growth largely by promoting dendritic cell (DC) maturation and cytotoxic T-cell activation. After combination with the immune checkpoint blockade (ICB), the therapeutic outcome is further amplified, accompanied by satisfactory abscopal and immune memory effects; the similar potency is proven in the "cold" 4T1 triple-negative breast tumor. In addition, Me exhibits good biosafety without significant acute or chronic toxicity. Briefly, this study turns waste into wealth by introducing sono-immunotherapy based on Microcystis that achieved encouraging therapeutic effects on cancer, which is expected to be translated into the clinic.

Deacetylation mechanism and potential reversal strategy of long QT syndrome on hERG K+ channel under hypoxia.

Clinically, hypoxia is a major risk factor for long QT syndrome (LQTS), which is associated with many diseases, such as myocardial ischemia. LQTS can be caused by the deficiency of hERG, a potassium ion channel that plays a key role in cardiac repolarization. Modifications such as acetylation of histones or non-histone proteins can affect the protein expression. In the present study, we explored the mechanism underlying hypoxia-induced LQTS and a potential reversal strategy. Experiments were performed under hypoxia to determine transcriptional and post-transcriptional expression changes. We used real-time PCR, chromatin immunoprecipitation assay, and western blotting to determine the histones acetylation in the hERG gene and the mechanism. Molecular docking, western blotting, IP, and patch -clamp assay were performed to determine the acetylation and ubiquitination levels of hERG protein and the mechanism. hERG mRNA and protein expression were found to decrease under hypoxia. The histone deacetylation level increased under hypoxia at both H3K27 and H4 of the hERG gene. HDAC1 and HDAC2 are the key enzymes for the mechanism. HDAC6 directly interacts with hERG. The acetylation level of hERG decreased and the ubiquitination level of hERG increased under hypoxia. The inhibitors of HDAC1, HDAC2, and HDAC6 could reverse the reduction of hERG mRNA and hERG protein expression under hypoxia. In conclusion, deacetylation of hERG gene-associated histones and hERG protein might be the mechanisms for LQTS in patients with hypoxia, and the inhibition of HDAC1, HDAC2, and HDAC6 might be a promising reversal strategy for reducing hERG expression under different pathological conditions.

[Polymorphisms analysis of mitochondrial DNA in coding area].

OBJECTIVE: To analyze mitochondrial DNA (mtDNA) polymorphisms in coding area and provide a theoretical basis for applying in forensic science. METHODS: The primers of 8162F/8483R and 13070F/13299R were designed according to the Anderson's sequence. Using PCR-sequencing method to detect polymorphisms of mtDNA nt8162-8483 and nt13070-13299. RESULTS: The lengths of the amplicons were 322 bp and 230 bp respectively. There were 24 mitochondrial haplotypes defined by 21 variable positions in both regions. The gene diversity was estimated at 0.751 1, and the probability of two randomly selected individuals having identical mtDNA types was 0.256 4. CONCLUSION: The polymorphic sites within mtDNA coding area can be useful in combination with mtDNA control region in order to increase the discrimination power.

Med-vest: A wearable sensory platform.

Sickle cell disease is a genetic mutation that causes sickling of the red blood cells, affecting between 90,000 and 100,000 Americans. Researchers must develop methods of data acquisition capable of maximizing both the amount of data being collected and types of data being collected to form the most accurate diagnosis and treatment for patients. Popular data acquisition forms are the use of mobile phones, sensory systems, and wearable technology. In this paper, we attempt to bridge the gap between the three, combining a wearable sensory system with the computation and communication power of mobile phones. We propose the application of sickle cell disease as a structure around which to design a textile-based data acquisition system.

Multi-channel LED light source for fluorescent agent aided minimally invasive surgery.

Cancer is one of the most common and deadly diseases around the world. Amongst all the different treatments of cancer such as surgery, chemotherapy and radiation therapy, surgical resection is the most effective. Successful surgeries greatly rely on the detection of the accurate tumor size and location, which can be enhanced by contrast agents. Commercial endoscope light sources, however, offer only white light illumination. In this paper, we present the development of a LED endoscope light source that provides 2 light channels plus white light to help surgeons to detect a clear tumor margin during minimally invasive surgeries. By exciting indocyanine green (ICG) and 5-Aminolaevulinic acid (ALA)-induced protoporphyrin IX (PPIX), the light source is intended to give the user a visible image of the tumor margin. This light source is also portable, easy to use and costs less than $300 to build.