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Frontiers in Pharmacology 2022Potassium ion (K) channels are pore-forming transmembrane proteins that control the transport of K ions. Medicinal plants are widely used as complementary therapies for... (Review)
Review
Potassium ion (K) channels are pore-forming transmembrane proteins that control the transport of K ions. Medicinal plants are widely used as complementary therapies for several disorders. Studies have shown that the modulation of K channels is most likely involved in various pharmacological effects of medicinal plants. This review aimed to evaluate the modulatory effects of medicinal plants and their active constituents on K channels under pathological conditions. This systematic review was prepared according to the Preferred Reporting Items for the Systematic Reviews and Meta-analyses (PRISMA) 2020 guideline. Four databases, including PubMed, Web of Science, embase, and Scopus, were searched. We identified 687 studies from these databases, from which we selected 13 studies for the review by using the Population, Intervention, Comparison, Outcomes, Study (PICOS) tool. The results of the 13 selected studies showed a modulatory effect of medicinal plants or their active constituents on ATP-sensitive potassium channels (K), and small (SK) and large (BK) conductance calcium-activated K channels in several pathological conditions such as nociception, brain ischemia, seizure, diabetes, gastric ulcer, myocardial ischemia-reperfusion, and hypertension via possible involvement of the nitric oxide/cyclic GMP pathway and protein kinase. K channels should be considered as significant therapeutic milestones in the treatment of several diseases. We believe that understanding the mechanism behind the interaction of medicinal plants with K channels can facilitate drug development for the treatment of various K channel-related disorders.
PubMed: 35273505
DOI: 10.3389/fphar.2022.831963 -
BMC Endocrine Disorders Nov 2021Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant type of diabetes. Pathogenic variants in fourteen genes are reported as causes of MODY. Its symptoms...
BACKGROUND
Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant type of diabetes. Pathogenic variants in fourteen genes are reported as causes of MODY. Its symptoms overlap with type 1 and type 2 diabetes. Reviews for clinical characteristics, diagnosis and treatments are available but a comprehensive list of genetic variants, is lacking. Therefore this study was designed to collect all the causal variants involved in MODY, reported to date.
METHODS
We searched PubMed from its date of inception to December 2019. The search terms we used included disease names and name of all the known genes involved. The ClinVar database was also searched for causal variants in the known 14 MODY genes.
RESULTS
The record revealed 1647 studies and among them, 326 studies were accessed for full-text. Finally, 239 studies were included, as per our inclusion criteria. A total of 1017 variants were identified through literature review and 74 unpublished variants from Clinvar database. The gene most commonly affected was GCK, followed by HNF1a. The traditional Sanger sequencing was used in 76 % of the cases and 65 % of the studies were conducted in last 10 years. Variants from countries like Jordan, Oman and Tunisia reported that the MODY types prevalent worldwide were not common in their countries.
CONCLUSIONS
We expect that this paper will help clinicians interpret MODY genetics results with greater confidence. Discrepancies in certain middle-eastern countries need to be investigated as other genes or factors, like consanguinity may be involved in developing diabetes.
Topics: Adaptor Proteins, Signal Transducing; Apoptosis Regulatory Proteins; Basic Helix-Loop-Helix Transcription Factors; Diabetes Mellitus, Type 2; Glucokinase; Hepatocyte Nuclear Factor 1-alpha; Hepatocyte Nuclear Factor 1-beta; Hepatocyte Nuclear Factor 4; High-Throughput Nucleotide Sequencing; Homeodomain Proteins; Humans; Insulin; Lipase; Paired Box Transcription Factors; Potassium Channels, Inwardly Rectifying; Repressor Proteins; Sequence Analysis, DNA; Sulfonylurea Receptors; Trans-Activators; src-Family Kinases
PubMed: 34763692
DOI: 10.1186/s12902-021-00891-7 -
Cells Oct 2021A serotonergic dysfunction has been largely postulated as the main cause of depression, mainly due to its effective response to drugs that increase the serotonergic...
A serotonergic dysfunction has been largely postulated as the main cause of depression, mainly due to its effective response to drugs that increase the serotonergic tone, still currently the first therapeutic line in this mood disorder. However, other dysfunctional pathomechanisms are likely involved in the disorder, and this may in part explain why some individuals with depression are resistant to serotonergic therapies. Among these, emerging evidence suggests a role for the astrocytic inward rectifier potassium channel 4.1 (Kir4.1) as an important modulator of neuronal excitability and glutamate metabolism. To discuss the relationship between Kir4.1 dysfunction and depression, a systematic review was performed according to the PRISMA statement. Searches were conducted across PubMed, Scopus, and Web of Science by two independent reviewers. Twelve studies met the inclusion criteria, analyzing Kir4.1 relationships with depression, through in vitro, in vivo, and investigations. Increasing, yet not conclusive, evidence suggests a potential pathogenic role for Kir4.1 upregulation in depression. However, the actual contribution in the diverse subtypes of the disorder and in the comorbid conditions, for example, the epilepsy-depression comorbidity, remain elusive. Further studies are needed to better define the clinical phenotype associated with Kir4.1 dysfunction in humans and the molecular mechanisms by which it contributes to depression and implications for future treatments.
Topics: Antidepressive Agents; Antidepressive Agents, Tricyclic; Astrocytes; Brain-Derived Neurotrophic Factor; Depression; Down-Regulation; Humans; Ketamine; Potassium Channels, Inwardly Rectifying; Selective Serotonin Reuptake Inhibitors; Up-Regulation
PubMed: 34685608
DOI: 10.3390/cells10102628 -
International Journal of Molecular... Oct 2021The Epithelial Sodium Channel/Degenerin (ENaC/DEG) family is a superfamily of sodium-selective channels that play diverse and important physiological roles in a wide...
The Epithelial Sodium Channel/Degenerin (ENaC/DEG) family is a superfamily of sodium-selective channels that play diverse and important physiological roles in a wide variety of animal species. Despite their differences, they share a high homology in the pore region in which the ion discrimination takes place. Although ion selectivity has been studied for decades, the mechanisms underlying this selectivity for trimeric channels, and particularly for the ENaC/DEG family, are still poorly understood. This systematic review follows PRISMA guidelines and aims to determine the main components that govern ion selectivity in the ENaC/DEG family. In total, 27 papers from three online databases were included according to specific exclusion and inclusion criteria. It was found that the G/SxS selectivity filter (glycine/serine, non-conserved residue, serine) and other well conserved residues play a crucial role in ion selectivity. Depending on the ion type, residues with different properties are involved in ion permeability. For lithium against sodium, aromatic residues upstream of the selectivity filter seem to be important, whereas for sodium against potassium, negatively charged residues downstream of the selectivity filter seem to be important. This review provides new perspectives for further studies to unravel the mechanisms of ion selectivity.
Topics: Amiloride; Animals; Epithelial Sodium Channels; Humans; Ion Transport; Lithium; Molecular Dynamics Simulation; Mutagenesis, Site-Directed; Protein Structure, Quaternary; Sodium
PubMed: 34681656
DOI: 10.3390/ijms222010998 -
Journal of Diabetes Research 2021Diabetes mellitus (DM) is a major chronic metabolic disease in the world, and the prevalence has been increasing rapidly in recent years. The channel of K plays an...
OBJECTIVES
Diabetes mellitus (DM) is a major chronic metabolic disease in the world, and the prevalence has been increasing rapidly in recent years. The channel of K plays an important role in the regulation of insulin secretion. The variants in gene encoding the SUR1 subunit of K could cause a variety of phenotypes, including neonatal diabetes mellitus (NDM) and -induced nonneonatal diabetes mellitus (-NNDM). Since the features of -NNDM have not been elucidated, this study is aimed at concluding the genetic features and clinical characteristics.
METHODS
We comprehensively reviewed the literature associated with -NNDM in the following databases: MEDLINE, PubMed, and Web of Science to investigate the features of -NNDM.
RESULTS
Based on a comprehensive literature search, we found that 87 probands with -NNDM carried 71 genetic variant alleles, 24% of whom carried inactivating variants, 24% carried activating variants, and the remaining 52% carried activating or inactivating variants. Nine of these variants were confirmed to be activating or inactivating through functional studies, while four variants (p.R370S, p.E1506K, p.R1418H, and p.R1420H) were confirmed to be inactivating. The phenotypes of -NNDM were variable and could also present with early hyperinsulinemia followed by reduced insulin secretion, progressing to diabetes later. They had a relatively high risk of microvascular complications and low prevalence of nervous disease, which is different from NDM.
CONCLUSIONS
Genetic testing is essential for proper diagnosis and appropriate treatment for patients with -NNDM. And further studies are required to determine the complex mechanism of the variants of -NNDM.
Topics: Animals; Blood Glucose; Diabetes Mellitus; Genetic Predisposition to Disease; Genetic Variation; Humans; Insulin; Phenotype; Sulfonylurea Receptors
PubMed: 34631896
DOI: 10.1155/2021/9479268 -
Disease-a-month : DM Feb 2022
Topics: Epithelium; Humans; Intestines; Magnesium; Magnesium Deficiency; RNA, Messenger; TRPM Cation Channels
PubMed: 34511254
DOI: 10.1016/j.disamonth.2021.101285 -
Archives of Biochemistry and Biophysics Oct 2021Mechanical environments were associated with alterations in bone metabolism. Ion channels present on bone cells are indispensable for bone metabolism and can be directly...
Mechanical environments were associated with alterations in bone metabolism. Ion channels present on bone cells are indispensable for bone metabolism and can be directly or indirectly activated by mechanical stimulation. This review aimed to discuss the literature reporting the mechanical regulatory effects of ion channels on bone cells and bone tissue. An electronic search was conducted in PubMed, Embase and Web of Science. Studies about mechanically induced alteration of bone cells and bone tissue by ion channels were included. Ion channels including TRP family channels, Ca release-activated Ca channels (CRACs), Piezo1/2 channels, purinergic receptors, NMDA receptors, voltage-sensitive calcium channels (VSCCs), TREK2 potassium channels, calcium- and voltage-dependent big conductance potassium (BK) channels, small conductance, calcium-activated potassium (SK) channels and epithelial sodium channels (ENaCs) present on bone cells and bone tissue participate in the mechanical regulation of bone development in addition to contributing to direct or indirect mechanotransduction such as altered membrane potential and ionic flux. Physiological (beneficial) mechanical stimulation could induce the anabolism of bone cells and bone tissue through ion channels, but abnormal (harmful) mechanical stimulation could also induce the catabolism of bone cells and bone tissue through ion channels. Functional expression of ion channels is vital for the mechanotransduction of bone cells. Mechanical activation (opening) of ion channels triggers ion influx and induces the activation of intracellular modulators that can influence bone metabolism. Therefore, mechanosensitive ion channels provide new insights into therapeutic targets for the treatment of bone-related diseases such as osteopenia and aseptic implant loosening.
Topics: Animals; Bone and Bones; Cell Line; Humans; Ion Channels; Mechanotransduction, Cellular; Receptors, Purinergic
PubMed: 34461086
DOI: 10.1016/j.abb.2021.109020 -
Frontiers in Genetics 2021Adverse drug reactions (ADR) are a major clinical problem accounting for significant hospital admission rates, morbidity, mortality, and health care costs. One-third of...
Adverse drug reactions (ADR) are a major clinical problem accounting for significant hospital admission rates, morbidity, mortality, and health care costs. One-third of people with diabetes experience at least one ADR. However, there is notable interindividual heterogeneity resulting in patient harm and unnecessary medical costs. Genomics is at the forefront of research to understand interindividual variability, and there are many genotype-drug response associations in diabetes with inconsistent findings. Here, we conducted a systematic review to comprehensively examine and synthesize the effect of genetic polymorphisms on the incidence of ADRs of oral glucose-lowering drugs in people with type 2 diabetes. A literature search was made to identify articles that included specific results of research on genetic polymorphism and adverse effects associated with oral glucose-lowering drugs. The electronic search was carried out on 3rd October 2020, through Cochrane Library, PubMed, and Web of Science using keywords and MeSH terms. Eighteen articles consisting of 10, 383 subjects were included in this review. Carriers of reduced-function alleles of organic cation transporter 1 (OCT 1, encoded by ) or reduced expression alleles of plasma membrane monoamine transporter (PMAT, encoded by ) or serotonin transporter (SERT, encoded by ) were associated with increased incidence of metformin-related gastrointestinal (GI) adverse effects. These effects were shown to exacerbate by concomitant treatment with gut transporter inhibiting drugs. The CYP2C9 alleles, (rs1799853C>T) and (rs1057910A>C) that are predictive of low enzyme activity were more common in subjects who experienced hypoglycemia after treatment with sulfonylureas. However, there was no significant association between sulfonylurea-related hypoglycemia and genetic variants in the ATP-binding cassette transporter sub-family C member 8 ()Potassium Inwardly Rectifying Channel Subfamily J Member 11 (. Compared to the wild type, the low enzyme activity C allele at CYP2C8 (rs1057910A>C) was associated with less weight gain whereas the C allele at rs6123045 in the gene was significantly associated with edema from rosiglitazone treatment. In spite of limited studies investigating genetics and ADR in diabetes, some convincing results are emerging. Genetic variants in genes encoding drug transporters and metabolizing enzymes are implicated in metformin-related GI adverse effects, and sulfonylurea-induced hypoglycemia, respectively. Further studies to investigate newer antidiabetic drugs such as DPP-4i, GLP-1RA, and SGLT2i are warranted. In addition, pharmacogenetic studies that account for race and ethnic differences are required.
PubMed: 34194474
DOI: 10.3389/fgene.2021.675053 -
Systems Biology in Reproductive Medicine Aug 2021Recent evidence suggests that gamete-imprinted genes play a role in embryo and placenta development and growth. This systematic review aimed to evaluate whether altered...
Recent evidence suggests that gamete-imprinted genes play a role in embryo and placenta development and growth. This systematic review aimed to evaluate whether altered methylation of sperm-imprinted genes associates with sperm DNA fragmentation (SDF), pregnancy loss rate and assisted reproductive technique (ART) outcome. To accomplish this, Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases were used for search strategy from each database inception until December 2020. Specific keywords were used. Studies satisfying the PECOS (Population, Exposure, Comparison/Comparator, Outcomes, Study design) model were retrieved. Ten studies could be included in the qualitative analysis. A significant association was reported between increased SDF rate and aberrant methylation of / and genes by two studies. A significantly lower methylation was found in patients with idiopathic recurrent pregnancy loss (RPL) and in infertile patients compared to fertile men. Methylation of /, and / were similar in patients with RPL and controls. The ART outcome was similar in patients with aberrant and normal methylation of /, and . By contrast, a study showed an association between altered GLT2 methylation and more inferior ART results. If further confirmed by well-sized studies, these data might be helpful to identify possible epigenetic predictors of ART outcome. Particularly, aberrant methylation of and genes might represent interesting targets that deserve further investigation.
Topics: Abortion, Habitual; DNA Methylation; Female; Genomic Imprinting; Humans; KCNQ1 Potassium Channel; Male; Pregnancy; RNA, Long Noncoding; Reproductive Techniques, Assisted; Spermatozoa
PubMed: 34080930
DOI: 10.1080/19396368.2021.1909667 -
Diabetes/metabolism Research and Reviews Nov 2021More than 1000 variants of the ATP-binding cassette transporter subfamily C member 8 (ABCC8) gene have been reported in neonatal diabetes mellitus. Up to now only 55... (Review)
Review
More than 1000 variants of the ATP-binding cassette transporter subfamily C member 8 (ABCC8) gene have been reported in neonatal diabetes mellitus. Up to now only 55 ABCC8 variants were associated with Maturity-Onset Diabetes of the Young 12 (MODY12). We present a c.3544C>T p.(Arg1182Trp) ABCC8 variant in a 35-year-old women who had pronounced microvascular diabetic complications and a charcot arthropathy necessitating a lower limb amputation. The unusual severity of the disease course prompted us to perform a systematic review of all genetic variants in MODY12. The present mutation has mostly been associated with neonatal diabetes and in only three papers reporting a MODY12. The 55 MODY12 variants show a large clinical heterogeneity, even in relatives with the same mutation, ranging from mild impaired glucose tolerance to severe insulin-dependent diabetes mellitus. HbA1c at diagnosis ranged from 5% to 14% and age at diagnosis ranged from 2 to 53 years. However, several case reports lack documentation of diabetic complications. Hence, more detailed reports remain necessary to improve insight in MODY12 pathophysiology and outcome. In this article current data regarding therapeutic management are provided, and key points to consider for the individual patient affected by MODY12 are presented.
Topics: Adult; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Humans; Infant, Newborn; Middle Aged; Mutation; Sulfonylurea Receptors
PubMed: 34014594
DOI: 10.1002/dmrr.3459