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IBRO Neuroscience Reports Dec 2022The environment has been implicated to be a strong determinant of brain health with higher risk of neurodegeneration. The drastic rise in the prevalence of... (Review)
Review
The environment has been implicated to be a strong determinant of brain health with higher risk of neurodegeneration. The drastic rise in the prevalence of neurodegenerative diseases (NDDs) including Alzheimer's disease (AD), Parkinson's disease (PD), autism spectrum disorder (ASD), multiple sclerosis (MS) etc., supports the idea that environmental factors may play a major role in NDDs aetiology. Nickel is one of the listed environmental metals reported to pose a serious threat to human health. This paper reported available studies on nickel level in NDDs covering both animal and human studies. Different databases were searched for articles reporting the main neurotoxicity mechanisms and the concentration of nickel in fluids and tissues of NDDs patients compared to controls. Data were extracted and synthesized by ensuring the articles were related to nickel and NDDs. Various mechanisms were reported as oxidative stress, disturbances in mitochondrial membrane potential, trace elements homeostasis destabilization, etc. Nickel was found elevated in biological fluids as blood, serum/plasma and CSF and in the brain of NDDs, as a consequence of unintentional exposure thorough nickel-contaminated air, food, water, and skin contact. In addition, after exposure to nickel, the concentration of markers of lipid peroxidation were increased, while some antioxidant defence systems decreased. Thus, the reduction in the exposure to nickel contaminant may hold a promise in reducing the incidence of NDDs.
PubMed: 35989698
DOI: 10.1016/j.ibneur.2022.07.005 -
Psychiatria Polska Apr 2022Currently, we observe a huge number of publications describing the role of glycine transporter (GlyT1) inhibitors in schizophrenia treatment. The concept of application... (Review)
Review
Currently, we observe a huge number of publications describing the role of glycine transporter (GlyT1) inhibitors in schizophrenia treatment. The concept of application for these drugs derives from the glutamatergic theory of schizophrenia. This theory explains psychotic disturbances as the consequence of NMDA receptor functioning defect. The role of the mentioned receptor depends mostly on the presence of cofactors. One such cofactor is the simplest aminoacid, glycine. This amino acid affects the glycine-binding site, located on the NR1 subunit of NMDAR and enables activation of the receptor. Substances enhancing the access of glycine to the receptor could hypothetically improve neuroplasticity. Higher efficacy of these neuroplastic processes may protect from cognitive deterioration and negative symptoms in the course of schizophrenia. In this article we present a systematic review of current literature on the topic of GlyT1 inhibitors in schizophrenia treatment (the state of literature as of November 2019). Firstly, we described the preclinical reasons for glycine enhancement use. Next, we used CINAHL, EMBASE, EMCARE, Medline, PsycINFO, PubMed and Google Scholar databases to extract and analyze evidence from clinical trials. GlyT1 inhibitors seem to have a potential in searching for novel substances in the treatment of negative symptoms, but their capacity to reduce cognitive deficits is not evidenced. So far, the clinical efficacy of several substances was proven, including N-methylglycine (sarcosine), bitopertin and derivatives obtained with chemical synthesis. Some of these substances demonstrate a beneficial clinical effect, but the number of published reports in this area is disproportionate to the value of evidence.
Topics: Glycine; Glycine Plasma Membrane Transport Proteins; Humans; Receptors, N-Methyl-D-Aspartate; Sarcosine; Schizophrenia
PubMed: 35988070
DOI: 10.12740/PP/OnlineFirst/126661 -
Frontiers in Plant Science 2022Root hairs are tubular outgrowths of epidermal cells that increase the root surface area and thereby make the root more efficient at absorbing water and nutrients. Their...
Root hairs are tubular outgrowths of epidermal cells that increase the root surface area and thereby make the root more efficient at absorbing water and nutrients. Their expansion is limited to the root hair apex, where growth is reported to take place in a pulsating manner. These growth pulses coincide with oscillations of the apoplastic and cytosolic pH in a similar way as has been reported for pollen tubes. Likewise, the concentrations of apoplastic reactive oxygen species (ROS) and cytoplasmic Ca oscillate with the same periodicity as growth. Whereas ROS appear to control cell wall extensibility and opening of Ca channels, the role of protons as a growth signal in root hairs is less clear and may differ from that in pollen tubes where plasma membrane H-ATPases have been shown to sustain growth. In this review, we outline our current understanding of how pH contributes to root hair development.
PubMed: 35968128
DOI: 10.3389/fpls.2022.949672 -
Frontiers in Immunology 2022Inflammatory arthritis is an inflammatory disease that involves the joints and surrounding tissues. Synovial hyperplasia often presents when joints become inflamed due...
Inflammatory arthritis is an inflammatory disease that involves the joints and surrounding tissues. Synovial hyperplasia often presents when joints become inflamed due to immune cell infiltration. Synovial membrane is an important as well as a highly specific component of the joint, and its lesions can lead to degeneration of the joint surface, causing pain and joint disability or affecting the patients' quality of life in severe cases. Synovial macrophages (SMs) are one of the cellular components of the synovial membrane, which not only retain the function of macrophages to engulf foreign bodies in the joint cavity, but also interact with synovial fibroblasts (SFs), T cells, B cells, and other inflammatory cells to promote the production of a variety of pro-inflammatory cytokines and chemokines, such as TNF-α, IL-1β, IL-8, and IL-6, which are involved in the pathogenic process of inflammatory arthritis. SMs from different tissue sources have differently differentiated potentials and functional expressions. This article provides a summary on studies pertaining to SMs in inflammatory arthritis, and explores their role in its treatment, in order to highlight novel treatment modalities for the disease.
Topics: Arthritis, Rheumatoid; Humans; Joints; Macrophages; Quality of Life; Synovial Membrane
PubMed: 35958604
DOI: 10.3389/fimmu.2022.905356 -
Experimental and Therapeutic Medicine Sep 2022The gallbladder undergoes different types of pathologies, ranging from inflammatory to preneoplasia and finally to malignant lesions. Gallbladder carcinoma can be highly...
The gallbladder undergoes different types of pathologies, ranging from inflammatory to preneoplasia and finally to malignant lesions. Gallbladder carcinoma can be highly invasive, and it is known that chronic inflammation of the gallbladder can lead to preneoplastic abnormalities and subsequently malignant phenotypes. Gallbladder neoplasia has a low incidence but is associated with a very poor prognosis. An early diagnosis is therefore extremely important in order to improve the prognosis of patients. Immunohistochemical markers of the mucin family can distinguish between different types of gallbladder lesions. Mucins are glycoproteins that can be attached to threonine residues that are -glycosylated (due to the hydroxyl group of this amino acid). Mucins are divided into two types: those that bind to the membrane, such as MUC1, and those that form gels or are secreted, such as MUC5AC. Various alterations in mucin expression have been revealed to be associated with the development of neoplasia, as they modulate cell growth, karyokinetic transformation, dedifferentiation, adhesion, invasion and immune surveillance. p53 is a tumor suppressor gene and is linked to the development of different types of neoplasia. The incidence of the p53 gene is variable in the pathophysiology of gallbladder cancer. Several studies have revealed an incidence of ~50% of the p53 gene in gallbladder tumors. Studying the immunohistochemical profile of mucins and the presence of different gene mutations in neoplastic lesions of the gallbladder and surrounding mucosa may contribute to the understanding of the pathophysiology of the disease and the mechanisms involved in tumor development, allowing the identification of patients at increased risk of developing neoplasia, thus leading to improved management.
PubMed: 35949333
DOI: 10.3892/etm.2022.11541 -
Molecular Psychiatry Aug 2023The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin... (Meta-Analysis)
Meta-Analysis
The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research. PubMed, EMBASE and PsycINFO were searched using terms appropriate to each area of research, from their inception until December 2020. Systematic reviews, meta-analyses and large data-set analyses in the following areas were identified: serotonin and serotonin metabolite, 5-HIAA, concentrations in body fluids; serotonin 5-HT receptor binding; serotonin transporter (SERT) levels measured by imaging or at post-mortem; tryptophan depletion studies; SERT gene associations and SERT gene-environment interactions. Studies of depression associated with physical conditions and specific subtypes of depression (e.g. bipolar depression) were excluded. Two independent reviewers extracted the data and assessed the quality of included studies using the AMSTAR-2, an adapted AMSTAR-2, or the STREGA for a large genetic study. The certainty of study results was assessed using a modified version of the GRADE. We did not synthesise results of individual meta-analyses because they included overlapping studies. The review was registered with PROSPERO (CRD42020207203). 17 studies were included: 12 systematic reviews and meta-analyses, 1 collaborative meta-analysis, 1 meta-analysis of large cohort studies, 1 systematic review and narrative synthesis, 1 genetic association study and 1 umbrella review. Quality of reviews was variable with some genetic studies of high quality. Two meta-analyses of overlapping studies examining the serotonin metabolite, 5-HIAA, showed no association with depression (largest n = 1002). One meta-analysis of cohort studies of plasma serotonin showed no relationship with depression, and evidence that lowered serotonin concentration was associated with antidepressant use (n = 1869). Two meta-analyses of overlapping studies examining the 5-HT receptor (largest n = 561), and three meta-analyses of overlapping studies examining SERT binding (largest n = 1845) showed weak and inconsistent evidence of reduced binding in some areas, which would be consistent with increased synaptic availability of serotonin in people with depression, if this was the original, causal abnormaly. However, effects of prior antidepressant use were not reliably excluded. One meta-analysis of tryptophan depletion studies found no effect in most healthy volunteers (n = 566), but weak evidence of an effect in those with a family history of depression (n = 75). Another systematic review (n = 342) and a sample of ten subsequent studies (n = 407) found no effect in volunteers. No systematic review of tryptophan depletion studies has been performed since 2007. The two largest and highest quality studies of the SERT gene, one genetic association study (n = 115,257) and one collaborative meta-analysis (n = 43,165), revealed no evidence of an association with depression, or of an interaction between genotype, stress and depression. The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.
Topics: Humans; Depression; Serotonin; Receptor, Serotonin, 5-HT1A; Tryptophan; Hydroxyindoleacetic Acid; Antidepressive Agents; Serotonin Plasma Membrane Transport Proteins
PubMed: 35854107
DOI: 10.1038/s41380-022-01661-0 -
Frontiers in Plant Science 2022Vegetables are a distinct collection of plant-based foods that vary in nutritional diversity and form an important part of the healthy diet of the human being. Besides...
Vegetables are a distinct collection of plant-based foods that vary in nutritional diversity and form an important part of the healthy diet of the human being. Besides providing basic nutrition, they have great potential for boosting human health. The balanced consumption of vegetables is highly recommended for supplementing the human body with better nutrition density, dietary fiber, minerals, vitamins, and bioactive compounds. However, the production and quality of fresh vegetables are influenced directly or indirectly by exposure to high temperatures or heat stress (HS). A decline in quality traits and harvestable yield are the most common effects of HS among vegetable crops. Heat-induced morphological damage, such as poor vegetative growth, leaf tip burning, and rib discoloration in leafy vegetables and sunburn, decreased fruit size, fruit/pod abortion, and unfilled fruit/pods in beans, are common, often rendering vegetable cultivation unprofitable. Further studies to trace down the possible physiological and biochemical effects associated with crop failure reveal that the key factors include membrane damage, photosynthetic inhibition, oxidative stress, and damage to reproductive tissues, which may be the key factors governing heat-induced crop failure. The reproductive stage of plants has extensively been studied for HS-induced abnormalities. Plant reproduction is more sensitive to HS than the vegetative stages, and affects various reproductive processes like pollen germination, pollen load, pollen tube growth, stigma receptivity, ovule fertility and, seed filling, resulting in poorer yields. Hence, sound and robust adaptation and mitigation strategies are needed to overcome the adverse impacts of HS at the morphological, physiological, and biochemical levels to ensure the productivity and quality of vegetable crops. Physiological traits such as the stay-green trait, canopy temperature depression, cell membrane thermostability, chlorophyll fluorescence, relative water content, increased reproductive fertility, fruit numbers, and fruit size are important for developing better yielding heat-tolerant varieties/cultivars. Moreover, various molecular approaches such as omics, molecular breeding, and transgenics, have been proved to be useful in enhancing/incorporating tolerance and can be potential tools for developing heat-tolerant varieties/cultivars. Further, these approaches will provide insights into the physiological and molecular mechanisms that govern thermotolerance and pave the way for engineering "designer" vegetable crops for better health and nutritional security. Besides these approaches, agronomic methods are also important for adaptation, escape and mitigation of HS protect and improve yields.
PubMed: 35837452
DOI: 10.3389/fpls.2022.878498 -
International Journal of Molecular... Jun 2022Extensive angiogenesis is a characteristic feature in the synovial tissue of rheumatoid arthritis (RA) from a very early stage of the disease onward and constitutes a... (Review)
Review
Extensive angiogenesis is a characteristic feature in the synovial tissue of rheumatoid arthritis (RA) from a very early stage of the disease onward and constitutes a crucial event for the development of the proliferative synovium. This process is markedly intensified in patients with prolonged disease duration, high disease activity, disease severity, and significant inflammatory cell infiltration. Angiogenesis is therefore an interesting target for the development of new therapeutic approaches as well as disease monitoring strategies in RA. To this end, nuclear imaging modalities represent valuable non-invasive tools that can selectively target molecular markers of angiogenesis and accurately and quantitatively track molecular changes in multiple joints simultaneously. This systematic review summarizes the imaging markers used for single photon emission computed tomography (SPECT) and/or positron emission tomography (PET) approaches, targeting pathways and mediators involved in synovial neo-angiogenesis in RA.
Topics: Arthritis, Rheumatoid; Biomarkers; Humans; Molecular Imaging; Neovascularization, Pathologic; Positron-Emission Tomography; Synovial Membrane
PubMed: 35806074
DOI: 10.3390/ijms23137071 -
Frontiers in Neuroscience 2022Neurodegenerative diseases (NDs) are generally considered proteinopathies but whereas this may initiate disease in familial cases, onset in sporadic diseases may...
Neurodegenerative diseases (NDs) are generally considered proteinopathies but whereas this may initiate disease in familial cases, onset in sporadic diseases may originate from a gradually disrupted organellar homeostasis. Herein, endolysosomal abnormalities, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and altered lipid metabolism are commonly observed in early preclinical stages of major NDs, including Parkinson's disease (PD) and Alzheimer's disease (AD). Among the multitude of underlying defective molecular mechanisms that have been suggested in the past decades, dysregulation of inter-organellar communication through the so-called membrane contact sites (MCSs) is becoming increasingly apparent. Although MCSs exist between almost every other type of subcellular organelle, to date, most focus has been put on defective communication between the ER and mitochondria in NDs, given these compartments are critical in neuronal survival. Contributions of other MCSs, notably those with endolysosomes and lipid droplets are emerging, supported as well by genetic studies, identifying genes functionally involved in lysosomal homeostasis. In this review, we summarize the molecular identity of the organelle interactome in yeast and mammalian cells, and critically evaluate the evidence supporting the contribution of disturbed MCSs to the general disrupted inter-organellar homeostasis in NDs, taking PD and AD as major examples.
PubMed: 35801175
DOI: 10.3389/fnins.2022.900338 -
Frontiers in Medicine 2022We evaluated the visual outcomes and complications of "endothelium-out" and "endothelium-in" Descemet membrane endothelial keratoplasty (DMEK) graft insertion techniques.
BACKGROUND
We evaluated the visual outcomes and complications of "endothelium-out" and "endothelium-in" Descemet membrane endothelial keratoplasty (DMEK) graft insertion techniques.
MATERIALS AND METHODS
Electronic searches were conducted in CENTRAL, Cochrane databases, PubMed, EMBASE, ClinicalTrials.gov. Study designs included clinical trials, comparative observational studies, and large case series (≥25 eyes). PRISMA guidelines were used for abstracting data and synthesis. Random-effects models were employed for meta-analyses.
RESULTS
21,323 eyes (95 studies) were included. Eighty-six studies reported on "endothelium-out" techniques; eight studies reported on "endothelium-in" techniques. One study compared "endothelium-out" to "endothelium-in" techniques. Eighteen "endothelium-out" studies reported that 42.5-85% of eyes achieved best-corrected visual acuity (BCVA) ≥20/25 at 6 months; pooled proportion of eyes achieving BCVA ≥20/25 at 6 months was 58.7% (95% CI 49.4-67.7%,15 studies). Three "endothelium-in" studies reported that 44.7-87.5% of eyes achieved BCVA of ≥20/25 at 6 months; pooled proportion of eyes achieving BCVA ≥20/25 at 6 months was 62.4% (95% CI 33.9-86.9%). Pooled mean endothelial cell loss was lower in the studies (28.1 ± 1.3%, 7 studies) compared to studies (36.3 ± 6.9%,10 studies) at 6 months ( = 0.018). Graft re-bubbling rates were higher in the "endothelium-out" studies (26.2%, 95% CI 21.9-30.9%, 74 studies) compared to "endothelium-in" studies (16.5%, 95% CI 8.5-26.4%, 6 studies), although statistical significance was not reached ( = 0.440). Primary graft failure rates were comparable between the two groups ( = 0.552). Quality of evidence was considered low and significant heterogeneity existed amongst the studies.
CONCLUSION
Reported rates of endothelial cell loss were lower in "endothelium-in" DMEK studies at 6 months compared to "endothelium-out" studies. Outcomes of "endothelium-in" techniques were otherwise comparable to those reported in "endothelium-out" studies. Given the technical challenges encountered in "endothelium-out" procedures, surgeons may consider "endothelium-in" techniques designed for easier intra-operative DMEK graft unfolding. "Endothelium-in" studies evaluating outcomes at longer time points are required before conclusive comparisons between the two techniques can be drawn.
PubMed: 35775001
DOI: 10.3389/fmed.2022.868533