Microglia, the resident immune cells of the brain, are increasingly implicated in the regulation of brain health and disease. Microglia perform multiple functions in the central nervous system, ...including surveillance, phagocytosis and release of a variety of soluble factors. Importantly, a majority of their functions are closely related to changes in their metabolism. This natural inter-dependency between core microglial properties and metabolism offers a unique opportunity to modulate microglial activities via nutritional or metabolic interventions. In this review, we examine the existing scientific literature to synthesize the hypothesis that microglial phagocytosis of amyloid beta (Aβ) aggregates in Alzheimer's disease (AD) can be selectively enhanced via metabolic interventions. We first review the basics of microglial metabolism and the effects of common metabolites, such as glucose, lipids, ketone bodies, glutamine, pyruvate and lactate, on microglial inflammatory and phagocytic properties. Next, we examine the evidence for dysregulation of microglial metabolism in AD. This is followed by a review of in vivo studies on metabolic manipulation of microglial functions to ascertain their therapeutic potential in AD. Finally, we discuss the effects of metabolic factors on microglial phagocytosis of healthy synapses, a pathological process that also contributes to the progression of AD. We conclude by enlisting the current challenges that need to be addressed before strategies to harness microglial phagocytosis to clear pathological protein deposits in AD and other neurodegenerative disorders can be widely adopted.
Environmental factors can change phenotypes in exposed individuals and offspring and involve the germline, likely via biological signals in the periphery that communicate with germ cells. Here, using ...a mouse model of paternal exposure to traumatic stress, we identify circulating factors involving peroxisome proliferator‐activated receptor (PPAR) pathways in the effects of exposure to the germline. We show that exposure alters metabolic functions and pathways, particularly lipid‐derived metabolites, in exposed fathers and their offspring. We collected data in a human cohort exposed to childhood trauma and observed similar metabolic alterations in circulation, suggesting conserved effects. Chronic injection of serum from trauma‐exposed males into controls recapitulates metabolic phenotypes in the offspring. We identify lipid‐activated nuclear receptors PPARs as potential mediators of the effects from father to offspring. Pharmacological PPAR activation in vivo reproduces metabolic dysfunctions in the offspring and grand‐offspring of injected males and affects the sperm transcriptome in fathers and sons. In germ‐like cells in vitro, both serum and PPAR agonist induce PPAR activation. Together, these results highlight the role of circulating factors as potential communication vectors between the periphery and the germline.
Synopsis
Exposure of mice to traumatic stress in early life leads to phenotypic changes that are transmitted to the progeny via mechanisms that remain poorly characterized. In vivo and in vitro findings from mice and humans implicate serum‐induced peroxisome proliferating‐activated receptor (PPAR) signaling in transmission of environmentally‐induced paternal traits via germline.
Lipid metabolism pathways are altered in plasma of adult male mice exposed to postnatal trauma and their adult offspring
Lipid metabolism is also altered in plasma and saliva of human orphan children.
Serum from mice with postnatal trauma activates PPAR nuclear receptors in spermatogonial cells in vitro.
Pharmacological PPAR activation in vivo recapitulates trauma‐induced metabolic phenotypes in adult mice and their offspring and sperm RNA alterations in fathers.
Injection of serum from trauma‐exposed males into control males recapitulates metabolic symptoms in their offspring.
In mice and humans, exposure to postnatal trauma triggers metabolic changes later in life, which are paternally transmitted to the offspring via PPAR nuclear receptor signaling activated by serum factors.
doi: https://doi.org/10.12669/pjms.38.7.6880
How to cite this:Jawaid SA, Jawaid M. Another landmark achievement by Pakistan Journal of Medical Sciences and the future challenges. Pak J Med Sci. ...2022;38(7):1727-1729. doi: https://doi.org/10.12669/pjms.38.7.6880
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
doi: https://doi.org/10.12669/pjms.38.7.6920
How to cite this:Jawaid SA. Publication audit & ever increasing problems faced by editors of Biomedical Journals. Pak J Med Sci. 2022;38(7):---. doi: ...https://doi.org/10.12669/pjms.38.7.6920
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Chemical sensors based on solution‐processed 2D nanomaterials represent an extremely attractive approach toward scalable and low‐cost devices. Through the implementation of real‐time impedance ...spectroscopy and development of a three‐element circuit model, redox exfoliated MoS2 nanoflakes demonstrate an ultrasensitive empirical detection limit of NO2 gas at 1 ppb, with an extrapolated ultimate detection limit approaching 63 ppt. This sensor construct reveals a more than three orders of magnitude improvement from conventional direct current sensing approaches as the traditionally dominant interflake interactions are bypassed in favor of selectively extracting intraflake doping effects. This same approach allows for an all solution‐processed, flexible 2D sensor to be fabricated on a polyimide substrate using a combination of graphene contacts and drop‐casted MoS2 nanoflakes, exhibiting similar sensitivity limits. Finally, a thermal annealing strategy is used to explore the tunability of the nanoflake interactions and subsequent circuit model fit, with a demonstrated sensitivity improvement of 2× with thermal annealing at 200 °C.
The implementation of a real‐time impedance spectroscopy approach results in ultrasensitive molecular sensors based on solution processed 2D nanomaterials. Through bypassing traditionally dominant interflake interactions and selectively extracting intraflake doping effects, detection of NO2 down to 1 ppb is readily achievable with an ultimate limit of detection of 63 ppt.
Many types of metal and semiconductor nanoparticles (NPs) are created via colloidal synthetic methods, which renders the materials hydrophobic. Such NPs are dispersed in water through surface organic ...cap exchange or by amphiphilic polymer encapsulation; often, water solubility is achieved via the presence of carboxylic acid functionalities on the solubilizing agents. While this renders the material water-soluble, subsequent functionalization of the systems can be very difficult. The most obvious method to derivatize carboxylic acid coated NPs is to conjugate chemical and biological moieties containing amine functionality to the NP surface using the water-soluble activator 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). However, the excess use of this reagent appears to cause complete and permanent precipitation of the NPs. We report here our method on the chemical and biological functionalization of a variety of semiconductor nanoparticle systems using novel carbodiimide reagents. These reagents do not cause precipitation even at high loading levels and can be used to efficiently functionalize carboxylic acid coated NPs.
doi: https://doi.org/10.12669/pjms.40.4.9346
How to cite this: Sattar K, Jawaid SA. From Challenges to Solutions: Mapping the Landscape of Medical Professionalism and Ethics in Pakistan. Pak J Med ...Sci. 2024;40(4):557-558. doi: https://doi.org/10.12669/pjms.40.4.9346
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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