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Frontiers in Bioengineering and... 2020Organ-on-chip (OOC) systems recapitulate key biological processes and responses exhibited by cells, tissues, and organs . Accordingly, these models of both health and... (Review)
Review
Organ-on-chip (OOC) systems recapitulate key biological processes and responses exhibited by cells, tissues, and organs . Accordingly, these models of both health and disease hold great promise for improving fundamental research, drug development, personalized medicine, and testing of pharmaceuticals, food substances, pollutants etc. Cells within the body are exposed to biomechanical stimuli, the nature of which is tissue specific and may change with disease or injury. These biomechanical stimuli regulate cell behavior and can amplify, annul, or even reverse the response to a given biochemical cue or drug candidate. As such, the application of an appropriate physiological or pathological biomechanical environment is essential for the successful recapitulation of behavior in OOC models. Here we review the current range of commercially available OOC platforms which incorporate active biomechanical stimulation. We highlight recent findings demonstrating the importance of including mechanical stimuli in models used for drug development and outline emerging factors which regulate the cellular response to the biomechanical environment. We explore the incorporation of mechanical stimuli in different organ models and identify areas where further research and development is required. Challenges associated with the integration of mechanics alongside other OOC requirements including scaling to increase throughput and diagnostic imaging are discussed. In summary, compelling evidence demonstrates that the incorporation of biomechanical stimuli in these OOC or microphysiological systems is key to fully replicating physiology in health and disease.
PubMed: 33363131
DOI: 10.3389/fbioe.2020.602646 -
IScience Sep 2021Neurons in the visual cortex quickly adapt to constant input, which should lead to perceptual fading within few tens of milliseconds. However, perceptual fading is...
Neurons in the visual cortex quickly adapt to constant input, which should lead to perceptual fading within few tens of milliseconds. However, perceptual fading is rarely observed in everyday perception, possibly because eye movements refresh retinal input. Recently, it has been suggested that amplitudes of large saccadic eye movements are scaled to maximally decorrelate presaccadic and postsaccadic inputs and thus to annul perceptual fading. However, this argument builds on the assumption that adaptation within naturally brief fixation durations is strong enough to survive any visually disruptive saccade and affect perception. We tested this assumption by measuring the effect of luminance adaptation on postsaccadic contrast perception. We found that postsaccadic contrast perception was affected by presaccadic luminance adaptation during brief periods of fixation. This adaptation effect emerges within 100 milliseconds and persists over seconds. These results indicate that adaptation during natural fixation periods can affect perception even after visually disruptive saccades.
PubMed: 34485868
DOI: 10.1016/j.isci.2021.102986 -
Journal of Biosciences Apr 2003The complement system is a potent innate immune mechanism consisting of cascades of proteins which are designed to fight against and annul intrusion of all the foreign... (Review)
Review
The complement system is a potent innate immune mechanism consisting of cascades of proteins which are designed to fight against and annul intrusion of all the foreign pathogens. Although viruses are smaller in size and have relatively simple structure, they are not immune to complement attack. Thus, activation of the complement system can lead to neutralization of cell-free viruses, phagocytosis of C3b-coated viral particles, lysis of virus-infected cells, and generation of inflammatory and specific immune responses. However, to combat host responses and succeed as pathogens, viruses not only have developed/adopted mechanisms to control complement, but also have turned these interactions to their own advantage. Important examples include poxviruses, herpesviruses, retroviruses, paramyxoviruses and picornaviruses. In this review, we provide information on the various complement evasion strategies that viruses have developed to thwart the complement attack of the host. A special emphasis is given on the interactions between the viral proteins that are involved in molecular mimicry and the complement system.
Topics: Animals; CD59 Antigens; Complement System Proteins; Humans; Immune System; Molecular Mimicry; Viral Proteins; Virus Physiological Phenomena
PubMed: 12734404
DOI: 10.1007/BF02970145 -
Frontiers in Oral Health 2023Although treatment modalities for head and neck cancer have evolved considerably over the past decades, survival rates have plateaued. The treatment options remained... (Review)
Review
Although treatment modalities for head and neck cancer have evolved considerably over the past decades, survival rates have plateaued. The treatment options remained limited to definitive surgery, surgery followed by fractionated radiotherapy with optional chemotherapy, and a definitive combination of fractionated radiotherapy and chemotherapy. Lately, immunotherapy has been introduced as the fourth modality of treatment, mainly administered as a single checkpoint inhibitor for recurrent or metastatic disease. While other regimens and combinations of immunotherapy and targeted therapy are being tested in clinical trials, adapting the appropriate regimens to patients and predicting their outcomes have yet to reach the clinical setting. Radiotherapy is mainly regarded as a means to target cancer cells while minimizing the unwanted peripheral effect. Radiotherapy regimens and fractionation are designed to serve this purpose, while the systemic effect of radiation on the immune response is rarely considered a factor while designing treatment. To bridge this gap, this review will highlight the effect of radiotherapy on the tumor microenvironment locally, and the immune response systemically. We will review the methodology to identify potential targets for therapy in the tumor microenvironment and the scientific basis for combining targeted therapy and radiotherapy. We will describe a current experience in preclinical models to test these combinations and propose how challenges in this realm may be faced. We will review new players in targeted therapy and their utilization to drive immunogenic response against head and neck cancer. We will outline the factors contributing to head and neck cancer heterogeneity and their effect on the response to radiotherapy. We will review methods to decipher intertumoral and intratumoral heterogeneity and how these algorithms can predict treatment outcomes. We propose that (a) the sequence of surgery, radiotherapy, chemotherapy, and targeted therapy should be designed not only to annul cancer directly, but to prime the immune response. (b) Fractionation of radiotherapy and the extent of the irradiated field should facilitate systemic immunity to develop. (c) New players in targeted therapy should be evaluated in translational studies toward clinical trials. (d) Head and neck cancer treatment should be personalized according to patients and tumor-specific factors.
PubMed: 37496754
DOI: 10.3389/froh.2023.1180869 -
Stress Biology Aug 2023Vesicle trafficking is an essential cellular process upon which many physiological processes of eukaryotic cells rely. It is usually the 'language' of communication... (Review)
Review
Vesicle trafficking is an essential cellular process upon which many physiological processes of eukaryotic cells rely. It is usually the 'language' of communication among the components of the endomembrane system within a cell, between cells and between a cell and its external environment. Generally, cells have the potential to internalize membrane-bound vesicles from external sources by endocytosis. Plants constantly interact with both mutualistic and pathogenic microbes. A large part of this interaction involves the exchange of transport vesicles between the plant cells and the microbes. Usually, in a pathogenic interaction, the pathogen releases vesicles containing bioactive molecules that can modulate the host immunity when absorbed by the host cells. In response to this attack, the host cells similarly mobilize some vesicles containing pathogenesis-related compounds to the pathogen infection site to destroy the pathogen, prevent it from penetrating the host cell or annul its influence. In fact, vesicle trafficking is involved in nearly all the strategies of phytopathogen attack subsequent plant immune responses. However, this field of plant-pathogen interaction is still at its infancy when narrowed down to plant-fungal pathogen interaction in relation to exchange of transport vesicles. Herein, we summarized some recent and novel findings unveiling the involvement of transport vesicles as a crosstalk in plant-fungal phytopathogen interaction, discussed their significance and identified some knowledge gaps to direct future research in the field. The roles of vesicles trafficking in the development of both organisms are also established.
PubMed: 37676627
DOI: 10.1007/s44154-023-00114-0 -
Vision (Basel, Switzerland) Jun 2022The main purpose of this work is to explore the Gestalt principle of similarity and to demonstrate that the use of this term alone is not sufficient to understand the...
The main purpose of this work is to explore the Gestalt principle of similarity and to demonstrate that the use of this term alone is not sufficient to understand the dynamics of grouping fully and correctly. More generally, this work aims to show that the Gestalt principle of similarity alone is not sufficient for a full understanding of perceptual organization occurring both in the classical and mostly in the new phenomena here presented. Limits and incompleteness of the similarity principle have suggested the basic, more general and stronger role of dissimilarity in perceptual grouping under a large variety of conditions. Dissimilarity was shown as a basic principle of figure-ground segregation, as a tool useful to create at will new groups and visual objects within patterns where they are totally invisible, as an attribute that is able to accentuate different shape components within the same object, as a way to distort shapes and create visual illusions, but also to reduce or annul them and, finally, to decompose, ungroup and reshape single objects. The results demonstrated the necessity to introduce a principle of dissimilarity that is complementary to similarity as already studied by Gestalt psychologists.
PubMed: 35893756
DOI: 10.3390/vision6030039 -
PloS One 2021In sub-Saharan Africa growing season precipitation is affected by climate change. Due to this, in Cameroon, it is uncertain how some crops are vulnerable to growing...
In sub-Saharan Africa growing season precipitation is affected by climate change. Due to this, in Cameroon, it is uncertain how some crops are vulnerable to growing season precipitation. Here, an assessment of the vulnerability of maize, millet, and rice to growing season precipitation is carried out at a national scale and validated at four sub-national scales/sites. The data collected were historical yield, precipitation, and adaptive capacity data for the period 1961-2019 for the national scale analysis and 1991-2016 for the sub-national scale analysis. The crop yield data were collected for maize, millet, and rice from FAOSTAT and the global yield gap atlas to assess the sensitivity both nationally and sub-nationally. Historical data on mean crop growing season and mean annul precipitation were collected from a collaborative database of UNDP/Oxford University and the climate portal of the World Bank to assess the exposure both nationally and sub-nationally. To assess adaptive capacity, literacy, and poverty rate proxies for both the national and regional scales were collected from KNOEMA and the African Development Bank. These data were analyzed using a vulnerability index that is based on sensitivity, exposure, and adaptive capacity. The national scale results show that millet has the lowest vulnerability index while rice has the highest. An inverse relationship between vulnerability and adaptive capacity is observed. Rice has the lowest adaptive capacity and the highest vulnerability index. Sub-nationally, this work has shown that northern maize is the most vulnerable crop followed by western highland rice. This work underscores the fact that at different scales, crops are differentially vulnerable due to variations in precipitation, temperature, soils, access to farm inputs, exposure to crop pest and variations in literacy and poverty rates. Therefore, caution should be taken when transitioning from one scale to another to avoid generalization. Despite these differences, in the sub-national scale, western highland rice is observed as the second most vulnerable crop, an observation similar to the national scale observation.
Topics: Cameroon; Climate Change; Crop Production; Crops, Agricultural; Millets; Oryza; Rain; Seasons; Socioeconomic Factors; Zea mays
PubMed: 34106980
DOI: 10.1371/journal.pone.0252335 -
Veterinary World Dec 2020Gentamicin (GM) is one of the most effective antibiotics for severe, life-threatening Gram-negative infections. Nevertheless, its clinical use has been restrained...
BACKGROUND AND AIM
Gentamicin (GM) is one of the most effective antibiotics for severe, life-threatening Gram-negative infections. Nevertheless, its clinical use has been restrained because of its nephrotoxic potential. Royal jelly (RJ) and aliskiren (ALK) can individually prevent such toxic effects. The aim of this study was to explore the protective effects of a combination treatment of RJ and ALK on GM-mediated nephrotoxicity.
MATERIALS AND METHODS
Thirty-two adult female. Wistar rats were divided equally into four groups: (I) Receiving normal saline; (II) GM (100 mg/kg, intraperitoneal [i.p.] injection); GM (100 mg/kg, i.p. injection) plus ALK (50 mg/kg, i.p. injection); and (IV) GM (100 mg/kg, i.p. injection) plus ALK (50 mg/kg, i.p. injection) in combination with RJ (150 mg/kg, orally). All treatments were administered daily for 10 days. The blood levels of creatinine, urea, uric acid, albumin, and total protein were measured. Then, the animals were sacrificed, and the kidneys were taken for histopathology.
RESULTS
Compared to normal control rats, GM-injected rats showed significantly (p<0.001) higher serum concentrations of uric acid, urea, and creatinine as well as evidently (p<0.001) lower blood levels of albumin and total protein. Moreover, GM administration was associated with significant renal histopathological changes. All these alterations were considerably (p<0.05) improved in GM-injected rats receiving ALK compared to rats receiving GM alone. However, when RJ was given in combination with ALK to GM-injected rats, it lessened the beneficial nephroprotective effects of both agents.
CONCLUSION
The combination treatment of RJ and ALK is not desirable for GM-induced nephrotoxicity. Further studies are crucial to accurately explore the precise mechanism of RJ antagonistic interaction with ALK.
PubMed: 33487984
DOI: 10.14202/vetworld.2020.2658-2662 -
Open Medicine (Warsaw, Poland) 2022Lung cancer (LC) is a prevailing primary tumor in the lung. lncRNA non-coding RNA activated by DNA damage (NORAD) is a popular target in human cancers. This experiment...
Lung cancer (LC) is a prevailing primary tumor in the lung. lncRNA non-coding RNA activated by DNA damage (NORAD) is a popular target in human cancers. This experiment is designed to probe the mechanism of lncRNA in LC progression. NORAD expression in normal lung epithelial cells and LC cells was examined and then silenced to assess its effect on LC cell proliferation, invasion, and migration. Subcellular localization of NORAD was analyzed through online databases and then corroborated by fractionation of nuclear and cytoplasmic RNA assay. The target binding relations between NORAD and miR-28-3p and between miR-28-3p and E2F2 were verified. Eventually, LC cells with NORAD silencing were transfected with miR-28-3p inhibitor or pcDNA3.1-E2F2 to measure LC cell proliferation, invasion, and migration. NORAD was overexpressed in LC cells and NORAD knockout led to suppressed LC cell proliferation, invasion, and migration. Besides, NORAD targeted miR-28-3p and miR-28-3p targeted E2F2 transcription. Inhibiting miR-28-3p or overexpressing E2F2 could both annul the inhibitory role of si-NORAD in LC cell proliferation, invasion, and migration. Generally, our findings demonstrated that NORAD competitively bound to miR-28-3p with E2F2, to promote LC cell progression.
PubMed: 36245705
DOI: 10.1515/med-2022-0538 -
The Journal of Neuroscience : the... Jul 2023Fear learning allows us to identify and anticipate aversive events and adapt our behavior accordingly. This is often thought to rely on associative learning mechanisms...
Fear learning allows us to identify and anticipate aversive events and adapt our behavior accordingly. This is often thought to rely on associative learning mechanisms where an initially neutral conditioned stimulus (CS) is repeatedly paired with an aversive unconditioned stimulus (US), eventually leading to the CS also being perceived as aversive and threatening. Importantly, however, humans also show verbal fear learning. Namely, they have the ability to change their responses to stimuli rapidly through verbal instructions about CS-US pairings. Past research on the link between experience-based and verbal fear learning indicated that verbal instructions about a reversal of CS-US pairings can fully override the effects of previously experienced CS-US pairings, as measured through fear ratings, skin conductance, and fear-potentiated startle. However, it remains an open question whether such instructions can also annul learned CS representations in the brain. Here, we used a fear reversal paradigm (female and male participants) in conjunction with representational similarity analysis of fMRI data to test whether verbal instructions fully override the effects of experienced CS-US pairings in fear-related brain regions or not. Previous research suggests that only the right amygdala should show lingering representations of previously experienced threat ("pavlovian trace"). Unexpectedly, we found evidence for the residual effect of prior CS-US experience to be much more widespread than anticipated, in the amygdala but also cortical regions like the dorsal anterior cingulate or dorsolateral prefrontal cortex. This finding shines a new light on the interaction of different fear learning mechanisms, at times with unexpected consequences. Humans are able to learn about aversive stimuli both from experience (i.e., repeated pairings of conditioned stimulus (CS) and unconditioned stimulus (US; pavlovian conditioning), and from verbal instructions about stimulus pairings. Understanding how experience-based and verbal learning processes interact is key for understanding the cognitive and neural underpinnings of fear learning. We tested whether prior aversive experiences (CS-US pairings) affected subsequent verbal learning, searching for lingering threat signals after verbal instructions reversed a CS from being threatening to being safe. While past research suggested such threat signals can only be found in the amygdala, we found evidence to be much more widespread, including the medial and lateral PFC. This highlights how experience-based and verbal learning processes interact to support adaptive behavior.
Topics: Humans; Male; Female; Conditioning, Classical; Fear; Conditioning, Operant; Brain; Learning
PubMed: 37414559
DOI: 10.1523/JNEUROSCI.0665-22.2023