Currently cancer treatment is in large part non-specific with respect to treatment. Medication is often harsh on patients, whereby they suffer several undesired side effects as a result. Carbon-based ...nanoparticles have attracted attention in recent years due to their ability to act as a platform for the attachment of several drugs and/or ligands. Relatively simple models are often used in cancer research, wherein carbon nanoparticles are conjugated to a ligand that is specific to an overexpressed receptor for imaging and drug delivery in cancer treatment. These carbon nanoparticles confer unique properties to the imaging or delivery vehicle due to their nontoxic nature and their high fluorescence qualities. Chief among the ongoing research within carbon-based nanoparticles emerge carbon dots (C-dots) and carbon nanotubes (CNTs). In this review, the aforementioned carbon nanoparticles will be discussed in their use within doxorubicin and gemcitabine based drug delivery vehicles, as well as the ligand-mediated receptor specific targeted therapy. Further directions of research in current field are also discussed.
Pathogen and danger recognition by the inflammasome activates inflammatory caspases that mediate inflammation and cell death. The cellular inhibitor of apoptosis proteins (cIAPs) function in ...apoptosis and innate immunity, but their role in modulating the inflammasome and the inflammatory caspases is unknown. Here we report that the cIAPs are critical effectors of the inflammasome and are required for efficient caspase-1 activation. cIAP1, cIAP2, and the adaptor protein TRAF2 interacted with caspase-1-containing complexes and mediated the activating nondegradative K63-linked polyubiquitination of caspase-1. Deficiency in cIAP1 (encoded by
Birc2) or cIAP2 (
Birc3) impaired caspase-1 activation after spontaneous or agonist-induced inflammasome assembly, and
Birc2
−/−
or
Birc3
−/−
mice or mice administered with an IAP antagonist had a dampened response to inflammasome agonists and were resistant to peritonitis. Our results describe a role for the cIAPs in innate immunity and further demonstrate the evolutionary conservation between cell death and inflammation mechanisms.
► cIAP1/2 are required for caspase-1 activation by the inflammasome ► cIAP1, cIAP2, and TRAF2 interact with caspase-1 and direct its K63 ubiquitination ►
Birc2
−/− and
Birc3
−/− mice are resistant to inflammasome-dependent peritonitis ► Administration of IAP inhibitor blocks IL-1β production and infiltration of Gr1
+ neutrophils
Abstract Background Kinematic alignment for total knee arthroplasty (TKA) may be one way of improving outcomes. Previous studies have either used patient-specific instrumentation, which adds cost, or ...standard instrumentation, which provides no intraoperative feedback on resection alignment. Hypothesis To determine if computer navigation could reproduce native patient anatomy and simplify ligament balance during TKA whilst giving satisfactory improvements in functional scores at early follow-up. Materials and methods Computer navigation was used for kinematic distal femoral and proximal tibial cuts in 100 consecutive and unselected TKAs. Resections were modified only if measured angles fell outside a pre-defined safe range of combined coronal orientation within ± 3 degrees of neutral and/or independent femoral or tibial cuts within ± 5 degrees. Pre- and postoperative measurements of the hip-knee-ankle (HKA) angle, the lateral distal femoral angle (LDFA) and the medial proximal tibial angle (MPTA) were taken using long-leg standing radiographs. Clinical evaluation was with the WOMAC and KOOS scales. Results Mean follow-up was 2.4 years (range 1.0–3.7, SD 0.8). The mean pre-op LDFA was 2.1 degrees valgus (9.2 valgus to 3.7 varus, SD 2.5) and 1.8 degrees valgus post-op (5.7 valgus to 4.2 varus, SD 2.0) ( P = 0.41). The mean pre-op MPTA was 3.0 degrees varus (10.6 valgus to 10.2 varus, SD 3.2) and 2.4 degrees varus post-op (4.0 valgus to 6.8 varus, SD 2.2) ( P = 0.03). The mean WOMAC score improved from 49.4 (29–85, SD 12.8) to 24.7 (0–73, SD 16.5) ( P < 0.001) and the mean KOOS score from 37.1 (7.2–77.2, SD 13.0) to 65.1 (26.8–100, SD 16) ( P < 0.001). Five knees (5%) required additional ligament release, four with valgus OA and one with varus OA. Two knees (2%) required lateral retinacular release for patellar tracking. Discussion Computer navigation for kinematic TKA provides the operating surgeon with full control and feedback at each step, whilst also allowing partial correction of more extreme anatomy that might be unsuitable for recreation during TKA. This technique helps to preserve ligament isometry and produces satisfactory improvements in functional scores. Level of evidence IV (retrospective case series review).
Rapid physical uterine clearance is paramount for fertility. Mares that are unable to clear the by-products of insemination or foaling quickly may develop post-mating-induced or acute endometritis. ...If endometritis is not promptly resolved, the infection can become chronic. Endometritis can be difficult to identify because clinical signs, ultrasonographic and laboratory findings can vary between uterine pathogens. Some micro-organisms are associated with an influx of neutrophils and fluid into the uterine lumen while others are associated with only heavy debris on cytological specimens. Identifying the inciting cause may require more than swabbing the endometrium. Culturing endometrial biopsy tissue or uterine fluids are more sensitive methods for identifying Escherichia coli than culture swab while endometrial cytology identifies twice as many mares with acute inflammation than uterine culture swab. While post-mating-induced endometritis is classically treated with uterine irrigation and ecbolics and acute endometritis is treated with either systemic or intra-uterine antibiotics, these therapies are not always effective in resolving chronic uterine inflammation or infections. Mucolytics can be used to break up mucus produced by an irritated endometrium, steroids can modulate the inflammatory response associated with insemination and buffered chelating agents can remove biofilm, a protective mechanism used primarily by gram-negative organisms and yeast to evade the host immune response.
Considerable efforts have been made to synthesize and characterize protein-nanoparticle conjugates (protein-NPs) for their promising applications in bionanotechnology. However, protein concentration ...determination in the protein-NPs has so far not been reported. In this Letter, we present a simple and nondestructive approach to quantify the protein concentration in the protein-NPs aqueous solution using circular dichroism (CD) spectroscopy. Carbon dots (∼4 nm), gold nanoparticles (∼10 nm), and polyethylene glycol (PEG, molecular weight ∼3000) were either physically mixed or covalently conjugated (not in the case of gold nanoparticles) with proteins (human transferrin, human serum albumin, and ovalbumin). We were able to quantify the protein concentration in the protein-nanoparticle conjugates using a calibration curve from the CD spectra.
Breast cancer (BC) is the most common malignancy in women worldwide, and one of the deadliest after lung cancer. Currently, standard methods for cancer therapy including BC are surgery followed by ...chemotherapy or radiotherapy. However, both chemotherapy and radiotherapy often fail to treat BC due to the side effects that these therapies incur in normal tissues and organs. In recent years, various nanoparticles (NPs) have been discovered and synthesized to be able to selectively target tumor cells without causing any harm to the healthy cells or organs. Therefore, NPs-mediated targeted drug delivery systems (DDS) have become a promising technique to treat BC. In addition to their selectivity to target tumor cells and reduce side effects, NPs have other unique properties which make them desirable for cancer treatment such as low toxicity, good compatibility, ease of preparation, high photoluminescence (PL) for bioimaging in vivo, and high loadability of drugs due to their tunable surface functionalities. In this study, we summarize with a critical analysis of the most recent therapeutic studies involving various NPs-mediated DDS as alternatives for the traditional treatment approaches for BC. It will shed light on the significance of NPs-mediated DDS and serve as a guide to seeking for the ideal methodology for future targeted drug delivery for an efficient BC treatment.
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Endometritis, a major cause of mare infertility arising from failure to remove bacteria, spermatozoa and inflammatory exudate post-breeding, is often undiagnosed. Defects in genital anatomy, ...myometrial contractions, lymphatic drainage, mucociliary clearance, cervical function, plus vascular degeneration and inflamm-ageing underlie susceptibility to endometritis. Diagnosis is made through detecting uterine fluid, vaginitis, vaginal discharge, short inter-oestrous intervals, inflammatory uterine cytology and positive uterine culture. However, these signs may be absent in subclinical cases. Hypersecretion of an irritating, watery, neutrophilic exudate underlies classic, easy-to-detect streptococcal endometritis. In contrast, biofilm production, tenacious exudate and focal infection may characterize subclinical endometritis, commonly caused by Gram-negative organisms, fungi and staphylococci. Signs of subclinical endometritis include excessive oedema post-mating and a white line between endometrial folds on ultrasound. In addition, cultures of uterine biopsy tissue or of small volume uterine lavage are twice as sensitive as guarded swabs in detecting Gram-negative organisms, while uterine cytology is twice as sensitive as culture in detecting endometritis. Uterine biopsy may detect deep inflammatory and degenerative changes, such as disruption of the elastic fibres of uterine vessels (elastosis), while endoscopy reveals focal lesions invisible on ultrasound. Mares with subclinical endometritis require careful monitoring by ultrasound post-breeding. Treatments that may be added to traditional therapies, such as post-breeding uterine lavage, oxytocin and intrauterine antibiotics, include lavage 1-h before mating, carbetocin, cloprostenol, cervical dilators, systemic antibiotics, intrauterine chelators (EDTA-Tris), mucolytics (DMSO, kerosene, N-acetylcysteine), corticosteroids (prednisolone, dexamethasone) and immunomodulators (cell wall extracts of Mycobacterium phlei and Propionibacterium acnes).
In this study, top-down syntheses of carbon dots (CDs) from four different carbon precursors, namely, carbon nano powders, graphite, graphene, and carbon nanotubes, were carried out. Systematic study ...demonstrated that the optical properties and surface functionalities of the CDs were quite similar and mainly influenced by the synthesis method, while the sizes, morphologies, chemical compositions, and core structures of the CDs were heavily influenced by the carbon precursors. On the basis of these studies, the formation processes and structural models of these four top-down CDs were proposed. The cell cytotoxicity and photothermal conversion efficiency of these CDs were also carefully evaluated, demonstrating their potential applications in photothermal therapy.
Bone tissue engineering (BTE) has received significant attention due to its enormous potential in treating critical‐sized bone defects and related diseases. Traditional materials such as metals, ...ceramics, and polymers have been widely applied as BTE scaffolds; however, their clinical applications have been rather limited due to various considerations. Recently, carbon‐based nanomaterials attract significant interests for their applications as BTE scaffolds due to their superior properties, including excellent mechanical strength, large surface area, tunable surface functionalities, high biocompatibility as well as abundant and inexpensive nature. In this article, recent studies and advancements on the use of carbon‐based nanomaterials with different dimensions such as graphene and its derivatives, carbon nanotubes, and carbon dots, for BTE are reviewed. Current challenges of carbon‐based nanomaterials for BTE and future trends in BTE scaffolds development are also highlighted and discussed.
Carbon‐based nanomaterials demonstrate enormous potential in bone tissue engineering (BTE) to treat critical‐sized bone defects due to their superior properties. Recent advancements of different dimensional carbon‐based nanomaterials (i.e., graphene oxide, carbon nanotubes, and carbon dots) in BTE are presented. Current challenges of BTE applications with carbon‐based nanomaterials and future trends of BTE are also highlighted and discussed.
Inflammatory caspases are essential effectors of inflammation and cell death. Here, we investigated their roles in colitis and colorectal cancer and report a bimodal regulation of intestinal ...homeostasis, inflammation and tumorigenesis by caspases-1 and −12.
Casp1
−/− mice exhibited defects in mucosal tissue repair and succumbed rapidly after dextran sulfate sodium administration. This phenotype was rescued by administration of exogenous interleukin-18 and was partially reproduced in mice deficient in the inflammasome adaptor ASC.
Casp12
−/− mice, in which the inflammasome is derepressed, were resistant to acute colitis and showed signs of enhanced repair. Together with their increased inflammatory response, the enhanced repair response of
Casp12
−/− mice rendered them more susceptible to colorectal cancer induced by azoxymethane (AOM)+DSS. Taken together, our results indicate that the inflammatory caspases are critical in the induction of inflammation in the gut after injury, which is necessary for tissue repair and maintenance of immune tolerance.
► Caspase-1 is critical for intestinal epithelial cell regeneration and tissue repair ► IL-18 production by the epithelium mediates caspase-1's cytoprotective effects ► The inflammasome adaptor ASC does not mediate caspase-1 functions in the gut ► Loss of caspase-12 predisposes to colitis-associated colorectal cancer
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