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Cancer immunotherapy evolved as a new treatment modality to eradicate tumor cells and has gained in popularity after its successful clinical transition. By activating antigen-presenting cells (APCs), and thus, inducing innate or adaptive immune responses, immunoadjuvants have become promising tools for cancer immunotherapy. Different types of immunoadjuvants such as toll-like receptor (TLR) agonists, exosomes, and metallic and plant-derived immunoadjuvants have been studied for their immunological effects. However, the clinical use of immunoadjuvants is limited by short response rates and various side-effects. The rapid progress made in the development of nanoparticle systems as immunoadjuvant carrier vehicles has provided potential carriers for cancer immunotherapy. In this review article, we describe different types of immunoadjuvants, their limitations, modes of action, and the reasons for their clinical adoption. In addition, we review recent progress made in the nanoparticle-based immunoadjuvant field and on the combined use of nanoparticle-based immunoadjuvants and chemotherapy, phototherapy, radiation therapy, and immune checkpoint inhibitor-based therapy. STATEMENT OF SIGNIFICANCE Cancer immunotherapy emerged as a new hope for treating malignant tumors. Different types of immunoadjuvants serve as an important tool for cancer immunotherapy by activating an innate or adaptive immune response. Limitation of free immunoadjuvant has paved the path for the development of nanoparticle-based immunoadjuvant therapy with the hope of prolonging the therapeutic efficacy. This review highlights the recent advancement made in nanoparticle-based immunoadjuvant therapy in modulating the adaptive and innate immune system. The application of the combinatorial approach of chemotherapy, phototherapy, radiation therapy adds synergy in nanoparticle-based immunoadjuvant therapy. It will broaden the reader's understanding on the recent progress made in immunotherapy with the aid of immunoadjuvant-based nanosystem.Polyetheretherketone has been widely used for bone defect repair, whereas failures may happen due to implant loosening and infection. Thus, PEEK implant with multi-function (osteogenesis, angiogenesis, and bacteria-killing) is essential to solve this problem. Herein, copper oxide microspheres (µCuO) decorated with silver nanoparticles (nAg) were constructed on porous PEEK surface via silk fibroin. In vitro studies highlighted the pH controlled release ability of this coating. It liberated a high dose of Cu2+ and Ag+ at low pH environment (pH 5.0), leading to 99.99% killing of planktonic bacteria and complete eradication of sessile bacteria, avoiding biofilm formation. Under physiological environment (pH 7.4), a lower amount of leaked metal ions induced promoted ALP production, collagen secretion, and calcium deposition, as well as NO production, which indicated potentiated osteogenesis and angiogenesis. In vivo results displayed the highest new bone volume around, and the appearance of new bone inside porous structure of, PEEK implant with this coating in rabbit tibia, signified the abilities of this coating to promote bone regeneration and osseointegration. Our study established solid support for implants with this coating to be a successful bone defect repair solution. STATEMENT OF SIGNIFICANCE In this study, CuO/Ag micro/nano particles were incorporated into the porous surface of PEEK through polydopamine and silk fibroin layers. selleck chemical The design of this coating conferred pH-controlled release behavior to Cu2+ and Ag+. High dose of metal ions were released at pH 5.0, which presented synergistic antibacterial ability and killed 99.99% of planktonic bacteria. Low concentration of metal ions were controlled by this coating at physiological environment, which potentiated osteodifferentiation of Ad-MSC in vitro and led to complete integration of implant with bone tissue in vivo.Solobacterium moorei is a strict anaerobic gram-positive rod. It is found in the human microbiota in different parts of the body, but it also appears to be an opportunistic pathogen in some infectious processes. We describe six cases of severe infections identified in 2016 in which S. moorei was isolated alone or in mixed culture involving other anaerobes or both aerobic and anaerobic bacteria. Three cases were associated with the oral cavity, including a middle ear infection, a wound infection after total laryngectomy, and a mandibular abscess as a result of bisphosphonate therapy. In the other three patients, the sites of infection had no connections with the oral cavity and included chronic osteomyelitis of the tibia, a superinfection of cutaneous tuberculosis associated with hidradenitis suppurativa, and the isolation of S. moorei from the blood culture of a cachectic man with several comorbidities. Based on our findings, S. moorei does not appear to be that virulent of a bacterium; except for the case with bacteraemia, S. moorei was recovered as a co-pathogen in patients with several immunosuppressive predisposing factors. We highlight the finding that the routine use of MALDI-TOF MS in microbiology laboratories can in a timely and detailed manner identify members of mixed infections involving different anaerobic bacteria that may be rare and difficult-to-culture and identify species, such as S. moorei.
The use of triple therapy with inhaled corticosteroids, long-acting beta-agonist and long-acting antimuscarinics has been shown to be beneficial in COPD patients who continue to have symptoms and exacerbations, despite receiving dual bronchodilator combinations. This study assessed the real-world effectiveness and safety of once-daily, fixed-dose combination of Tiotropium/Formoterol/Ciclesonide (TFC) (18 mcg/12 mcg/400 mcg) via dry powder inhaler (DPI) or metered dose inhaler (MDI) in patients with COPD.
In this 24-week, open-label, prospective, non-comparative, multicentre, real-world study, COPD patients requiring triple therapy as judged by their physician, were enrolled. The primary endpoint was mean change from baseline in pre-dose Forced Expiratory Volume in 1s (FEV
) at week 24. Pre and post-dose (30min) FEV
, Forced Vital capacity (FVC), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) score and safety were also evaluated. A post-hoc analysis was conducted to evaluate the efficacy of the triple drug combination among smoker and non-smoker COPD patients.
My Website: https://www.selleckchem.com/products/alkbh5-inhibitor-1-compound-3.html
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