The primary malignancy of liver, known as hepatocellular carcinoma (HCC), comprises 9% of all hepatobiliary carcinomas. A steady rise has also been observed in adenocarcinoma (ADC) of the liver and ampullary carcinoma (AMC), ascending to 0.5% of gastrointestinal malignancies. Hepatobiliary carcinomas consist of 13% of all cancer occurrences worldwide. Purinergic receptor-based signaling holds the therapeutic potential based on its role in cell proliferation of several carcinomas. An altered ATP concentration in nanomoles may lead towards crucial changes in cancer growth patterns in liver tissue. A total of 40 tissue samples were collected (20 samples of HCC, 10 samples of ADC, and 10 samples of AMC) from patients that underwent surgery. P2X4 and P2X7 receptors exhibited significantly increased expression in HCC, ADC, and AMC samples as compared with the control tissue samples. While ADC and AMC samples showed higher expression of P2X4 and P2X7 than the control, statistically, HCC samples exhibited the most significant expression of both P2X4 and P2X7 receptors than control tissues. It may be inferred that higher expression of P2X4 and P2X7 receptors is significantly associated with the upregulated cellular stress leading to inflammation and it is plausible that both these receptors may be used in diagnostic, prognostic, and therapeutic tools for carcinoma studies in the future.
The sudden emergence of infectious pathogens such as Zika virus (ZIKV) holds global health concerns. Recent dissemination of ZIKV from Pacific to Americas with an upsurge of congenital anomalies and Guillain Barre Syndrome (GBS) in adults has created an alarming situation. High-throughput studies are in progress to understand ZIKV's mode of pathogenesis and mechanism of immune escape, yet the pathogenesis remains obscure. Mainly ZIKV's envelope (E) protein and nonstructural proteins (mainly NS1 and NS5) manipulate host cell to support viral immune escape by modulation of the interferon pathway and complement antagonism. The development of direct therapeutics for ZIKV infection is required to overcome the rapidly evolving viral threat. Currently, the existing strategies for ZIKV treatment are only supportive. Although, there is no prophylactic or therapeutic vaccine presently available, however, recent efforts have brought up ZIKV vaccines into clinical trial phase 1. This review presents the highlights of recent advances in understanding immune evasion strategies adapted by ZIKV and existing therapies against the virus.
The cellular microenvironment is influenced explicitly by the extracellular matrix (ECM), the main tissue support biomaterial, as a decisive factor for tissue growth patterns. The recent emergence of hepatic microphysiological systems (MPS) provide the basic physiological emulation of the human liver for drug screening. However, engineering microfluidic devices with standardized surface coatings of ECM may improve MPS-based organ-specific emulation for improved drug screening. The influence of surface coatings of different ECM types on tissue development needs to be optimized. Additionally, an intensity-based image processing tool and transepithelial electrical resistance (TEER) sensor may assist in the analysis of tissue formation capacity under the influence of different ECM types. The current study highlights the role of ECM coatings for improved tissue formation, implying the additional role of image processing and TEER sensors. We studied hepatic tissue formation under the influence of multiple concentrations of Matrigel, collagen, fibronectin, and poly-L-lysine. Based on experimental data, a mathematical model was developed, and ECM concentrations were validated for better tissue development. TEER sensor and image processing data were used to evaluate the development of a hepatic MPS for human liver physiology modeling. Image analysis data for tissue formation was further strengthened by metabolic quantification of albumin, urea, and cytochrome P450. Standardized ECM type for MPS may improve clinical relevance for modeling hepatic tissue microenvironment, and image processing possibly enhance the tissue analysis of the MPS.
Renal ischemic-reperfusion injury decreases the chances
of long-term
kidney graft survival and may lead to the loss of a transplanted kidney.
During organ excision, the cycle of warm ischemia from the donor and
cold ischemia is due to storage in a cold medium after revascularization
following organ transplantation. The reperfusion of the kidney graft
activates several pathways that generate reactive oxygen species,
forming a hypoxic-reperfusion injury. Animal models are generally
used to model and investigate renal hypoxic-reperfusion injury. However,
these models face ethical concerns and present a lack of robustness
and intraspecies genetic variations, among other limitations. We introduce
a microfluidics-based renal hypoxic-reperfusion (RHR) injury-on-chip
model to overcome current limitations. Primary human renal proximal
tubular epithelial cells and primary human endothelial cells were
cultured on the apical and basal sides of a porous membrane. Hypoxic
and normoxic cell culture media were used to create the RHR injury-on-chip
model. The disease model was validated by estimating various specific
hypoxic biomarkers of RHR. Furthermore, retinol, ascorbic acid, and
combinational doses were tested to devise a therapeutic solution for
RHR. We found that combinational vitamin therapy can decrease the
chances of RHR injury. The proposed RHR injury-on-chip model can serve
as an alternative to animal testing for injury investigation and the
identification of new therapies.
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