INFLUENCE OF PROBIOTIC SUPPLEMENTATION ON CLIMACTERIC SYMPTOMS IN MENOPAUSAL WOMEN-A MINI REVIEW

Menopause (MP) is a natural physiological event of woman’s life and is defined as the absence of menstrual periods for at least twelve months and loss of function of ovarian. The common symptoms of MP are irregular vaginal bleeding, hot flushes especially in head and chest, night sweats, insomnia, vaginal and urinary symptoms, cognitive dysfunction, increased cancer risk, osteopenia, high blood pressure, diabetes, and cardiovascular diseases. Microbiome has been associated with several health benefits. Probiotic supplementation helps to enhance the quality of microbiome thereby confers the health benefits to the host system. The microbiome, hormone (estrogen) changes, and probiotic intervention are related to the health status of the female reproductive system. The vaginal microbiome (VM) play a critical role in female reproductive health and MP, which can be greatly influenced by probiotics, and other medicine especially antibiotics and hormone therapy. The role of VM in supporting vaginal health is not clear and debatable. Understanding the role of vaginal Lactobacillus could expose the pathogenesis of vaginal dysbiosis, which helps to improve diagnostic and therapeutic strategies for several dysbiosis associated health issues and menopause-related symptoms. Recent studies suggested that the intervention of probiotic preparation with or without nutraceutical formulation (mostly with isoflavones) improve the health status of menopausal women. The mechanism of probiotics mediated health improvement in menopausal women is not yet described clearly. Several controversies are there on the link between probiotic, gut microbiota, vaginal microbiota, and estrogen deficit. The present review summarizes the influence of probiotic supplementation on climacteric symptoms in menopausal women. The literature search was made in Scopus, Google Scholar, PubMed using the keywords “probiotics” and “menopause”. The documents were carefully checked for the relevance to the current manuscript, and the selection was made without any restriction in the year of publication.

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Calcineurin homologous proteins regulate the membrane localization and activity of sodium/proton exchangers in C. elegans

AJP Cell Physiology ◽

10.1152/ajpcell.00291.2015 ◽

2016 ◽

Vol 310 (3) ◽

pp. C233-C242 ◽

Cited By ~ 4

Author(s):

Erik Allman ◽

Qian Wang ◽

Rachel L. Walker ◽

Molly Austen ◽

Maureen A. Peters ◽

...

Keyword(s):

Genetic Model ◽

Expression Patterns ◽

Critical Role ◽

Model Organism ◽

Loss Of Function ◽

Homologous Proteins ◽

Relative Significance ◽

C Elegans ◽

Fluorescent Tags

Calcineurin B homologous proteins (CHP) are N-myristoylated, EF-hand Ca2+-binding proteins that bind to and regulate Na+/H+ exchangers, which occurs through a variety of mechanisms whose relative significance is incompletely understood. Like mammals, Caenorhabditis elegans has three CHP paralogs, but unlike mammals, worms can survive CHP loss-of-function. However, mutants for the CHP ortholog PBO-1 are unfit, and PBO-1 has been shown to be required for proton signaling by the basolateral Na+/H+ exchanger NHX-7 and for proton-coupled intestinal nutrient uptake by the apical Na+/H+ exchanger NHX-2. Here, we have used this genetic model organism to interrogate PBO-1's mechanism of action. Using fluorescent tags to monitor Na+/H+ exchanger trafficking and localization, we found that loss of either PBO-1 binding or activity caused NHX-7 to accumulate in late endosomes/lysosomes. In contrast, NHX-2 was stabilized at the apical membrane by a nonfunctional PBO-1 protein and was only internalized following its complete loss. Additionally, two pbo-1 paralogs were identified, and their expression patterns were analyzed. One of these contributed to the function of the excretory cell, which acts like a kidney in worms, establishing an alternative model for testing the role of this protein in membrane transporter trafficking and regulation. These results lead us to conclude that the role of CHP in Na+/H+ exchanger regulation differs between apical and basolateral transporters. This further emphasizes the importance of proper targeting of Na+/H+ exchangers and the critical role of CHP family proteins in this process.

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Continuing Medical Education via Telemedicine and Sustainable Improvements to Health

International Journal of Telemedicine and Applications ◽

10.1155/2016/2424709 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6

Author(s):

Fuhmei Wang

Keyword(s):

Medical Education ◽

Health Status ◽

Panel Data ◽

Continuing Medical Education ◽

Quantitative Relationship ◽

Ordinary Least Squares ◽

Learning Processes ◽

Health Improvement ◽

Optimal Learning

Background.This research aims to investigate the quantitative relationship between telemedicine and online continuing medical education (CME) and to find the optimal CME lectures to be delivered via telemedicine to improve the population’s health status.Objective.This study examines the following:(1)What factors foster learning processes in CME via telemedicine?(2)What is the possible role of online CME in health improvement? And(3)How optimal learning processes can be integrated with various health services?Methods.By applying telemedicine experiences in Taiwan over the period 1995–2004, this study uses panel data and the method of ordinary least squares to embed an adequate set of phenomena affecting the provision of online CME lectures versus health status.Results.Analytical results find that a nonlinear online CME-health nexus exists. Increases in the provision of online CME lectures are associated with health improvements. However, after the optimum has been reached, greater provision of online CME lectures may be associated with decreasing population health.Conclusion.Health attainment could be partially viewed as being determined by the achievement of the appropriately providing online CME lectures. This study has evaluated the population’s health outcomes and responded to the currently inadequate provision of online CME lectures via telemedicine.

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Heterozygous variants in KCNC2 cause a broad spectrum of epilepsy phenotypes associated with characteristic functional alterations

10.1101/2021.05.21.21257099 ◽

2021 ◽

Author(s):

Niklas Schwarz ◽

Simone Seiffert ◽

Manuela Pendziwiat ◽

Annika Rademacher ◽

Tobias Bruenger ◽

...

Keyword(s):

Functional Analysis ◽

De Novo ◽

Critical Role ◽

Specific Response ◽

Loss Of Function ◽

Causative Gene ◽

Characteristic Functional ◽

Research Collaborations ◽

The Brain

Background KCNC2 encodes a member of the shaw-related voltage-gated potassium channel family (KV3.2), which are important for sustained high-frequency firing and optimized energy efficiency of action potentials in the brain. Methods Individuals with KCNC2 variants detected by exome sequencing were selected for clinical, further genetic and functional analysis. The cases were referred through clinical and research collaborations in our study. Four de novo variants were examined electrophysiologically in Xenopus laevis oocytes. Results We identified novel KCNC2 variants in 27 patients with various forms of epilepsy. Functional analysis demonstrated gain-of-function in severe and loss-of-function in milder phenotypes as the underlying pathomechanisms with specific response to valproic acid. Conclusion These findings implicate KCNC2 as a novel causative gene for epilepsy emphasizing the critical role of KV3.2 in the regulation of brain excitability with an interesting genotype-phenotype correlation and a potential concept for precision medicine.

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DUSP12 regulates the tumorigenesis and prognosis of hepatocellular carcinoma

PeerJ ◽

10.7717/peerj.11929 ◽

2021 ◽

Vol 9 ◽

pp. e11929

Author(s):

Gaoda Ju ◽

Tianhao Zhou ◽

Rui Zhang ◽

Xiaozao Pan ◽

Bing Xue ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

T Cells ◽

Immune Cells ◽

Malignant Tumors ◽

Critical Role ◽

Normal Liver ◽

Functional Enrichment ◽

Loss Of Function ◽

Liver Tissues

Background Dual specificity protein phosphatase (DUSP)12 is an atypical member of the protein tyrosine phosphatase family, which are overexpressed in multiple types of malignant tumors. This protein family protect cells from apoptosis and promotes the proliferation and motility of cells. However, the pathological role of DUSP12 in hepatocellular carcinoma (HCC) is incompletely understood. Methods We analyzed mRNA expression of DUSP12 between HCC and normal liver tissues using multiple online databases, and explored the status of DUSP12 mutants using the cBioPortal database. The correlation between DUSP12 expression and tumor-infiltrating immune cells was demonstrated using the Tumor Immune Estimation Resource database and the Tumor and Immune System Interaction Database. Loss of function assay was utilized to evaluate the role of DUSP12 in HCC progression. Results DUSP12 had higher expression along with mRNA amplification in HCC tissues compared with those in normal liver tissues, which suggested that higher DUSP12 expression predicted shorter overall survival. Analyses of functional enrichment of differentially expressed genes suggested that DUSP12 regulated HCC tumorigenesis, and that knockdown of DUSP12 expression by short hairpin (sh)RNA decreased the proliferation and migration of HCC cells. Besides, DUSP12 expression was positively associated with the infiltration of cluster of differentiation (CD)4+ T cells (especially CD4+ regulatory T cells), macrophages, neutrophils and dendritic cells. DUSP12 expression was positively associated with immune-checkpoint moieties, and was downregulated in a C3 immune-subgroup of HCC (which had the longest survival). Conclusion These data suggest that DUSP12 may have a critical role in the tumorigenesis, infiltration of immune cells, and prognosis of HCC.

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General Health Benefits of Pranayama W.S.R. to Effects on Respiratory System: An Ayurveda Review

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v10i1-s.3894 ◽

2020 ◽

Vol 10 (1-s) ◽

pp. 215-217

Author(s):

Yogeshwar Ashok Tikle

Keyword(s):

Health Status ◽

Respiratory System ◽

General Health ◽

Health Benefits ◽

Respiratory Control ◽

Spiritual Health ◽

Therapeutic Measure ◽

Pathological Conditions ◽

Three Stages

Pranayama is traditional techniques practicing from ancient time of Indian civilization; it establishes balances of body, mind and spiritual health. Pranayama used for various purposes such as; maintaining health status & beauty, delaying age and as therapeutic measure against many pathological conditions. Pranayama involves three stages of respiratory practice; Puraka (inhalation), Kumbhaka (retention) and Rechaka (exhalation). These stages when practices with respiratory control then offer several health benefits. Pranayama improves circulatory process of body, boost respiratory system and helps in pathological conditions like; asthma and rhinitis. Present article summarizes role of Pranayama on respiratory system and related diseases. Keywords: Pranayama, Respiratory System, Puraka, Kumbhaka and Rechaka.

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Critical Role of E1623 Residue in S3-S4 Loop of Nav1.1 Channel and Correlation Between Nature of Substitution and Functional Alteration

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.797628 ◽

2022 ◽

Vol 14 ◽

Author(s):

Tao Su ◽

Meng-Long Chen ◽

Li-Hong Liu ◽

Hen Meng ◽

Bin Tang ◽

...

Keyword(s):

Current Density ◽

Genetic Disorders ◽

Critical Role ◽

Missense Variant ◽

Loss Of Function ◽

Channel Conductance ◽

Peak Current Density ◽

Functional Changes ◽

Functional Alteration

Objective: An overwhelming majority of the genetic variants associated with genetic disorders are missense. The association between the nature of substitution and the functional alteration, which is critical in determining the pathogenicity of variants, remains largely unknown. With a novel missense variant (E1623A) identified from two epileptic cases, which occurs in the extracellular S3-S4 loop of Nav1.1, we studied functional changes of all latent mutations at residue E1623, aiming to understand the relationship between substitution nature and functional alteration.Methods: Six latent mutants with amino acid substitutions at E1623 were generated, followed by measurements of their electrophysiological alterations. Different computational analyses were used to parameterize the residue alterations.Results: Structural modeling indicated that the E1623 was located in the peripheral region far from the central pore, and contributed to the tight turn of the S3-S4 loop. The E1623 residue exhibited low functional tolerance to the substitutions with the most remarkable loss-of-function found in E1623A, including reduced current density, less steady-state availability of activation and inactivation, and slower recovery from fast inactivation. Correlation analysis between electrophysiological parameters and the parameterized physicochemical properties of different residues suggested that hydrophilicity of side-chain at E1623 might be a crucial contributor for voltage-dependent kinetics. However, none of the established algorithms on the physicochemical variations of residues could well predict changes in the channel conductance property indicated by peak current density.Significance: The results established the important role of the extracellular S3-S4 loop in Nav1.1 channel gating and proposed a possible effect of local conformational loop flexibility on channel conductance and kinetics. Site-specific knowledge of protein will be a fundamental task for future bioinformatics.

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Determinating the role of the E3 Ubiquitin Ligase Ariadne 2 in mammalian systemss

Clinical & Investigative Medicine ◽

10.25011/cim.v30i4.2863 ◽

2007 ◽

Vol 30 (4) ◽

pp. 87

Author(s):

A. E. Lin ◽

A. Wakeham ◽

A. You-Ten ◽

G. Wood ◽

T. W. Mak

Keyword(s):

Function Analysis ◽

Critical Role ◽

Ring Finger ◽

E3 Ligase ◽

Signalling Pathways ◽

Loss Of Function ◽

In Vivo Models

Ubiquitination is a eukaryotic process of selective proteolysis, where a highly conserved ubiquitin protein is selectively added as a chain to the targeted to a protein for degradation. In recent years, the process of ubiquitination has been shown to be a critical mechanism that can affect essential signalling pathways, including apoptosis, cell cycle arrest and induction of the inflammatory response. Thus, alterations in the ubiquitination process can alter signalling pathways pivotal to numerous disease pathologies. This is clearly demonstrated in perturbations of ubiquitination in the NFκB giving rise to cancer and other immunological disease processes. To gain insight into pathways that require regulation by ubiquitination, our lab has directed focus on the highly conserved E3 ligase, Ariadne 2. Ariadne 2 is characterized as a putative RING finger E3 ligase and is part of the family of highly conserved RBR (RING-B-Box-RING) superfamily. The role of Ariadne 2 has been well studied in Drosophila melanogaster, however, little is known of the function of Ariadne 2 in mammalian systems. Therefore, the main objectives of the project are as follows: To determine the biological role of Ariadne 2, the role of Ariadne 2 in development and differentiation, and the consequences of in vivo loss of Ariadne 2 expression. We are currently investigating the role of Ariadne 2 as an E3 ligase and its involvement in the immune response. To date, we have shown that Ariadne 2 is ubiquitously expressed, especially in the brain, heart, spleen and thymus. For in vivo loss of function analysis, mice were generated by homologous recombination to be deficient for Ariadne 2. These deficient mice die prematurely soon after birth, suggesting a critical role for Ariadne 2 in development and survival. We are currently focusing on the role of Ariadne 2 in development and it’s role in immune pathologies, in particular, spontaneous autoimmunity, using both in vitro studies and in vivo models.

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MAB21L1 loss of function causes a syndromic neurodevelopmental disorder with distinctive cerebellar, ocular, craniofacial and genital features (COFG syndrome)

Journal of Medical Genetics ◽

10.1136/jmedgenet-2018-105623 ◽

2018 ◽

Vol 56 (5) ◽

pp. 332-339 ◽

Cited By ~ 1

Author(s):

Abolfazl Rad ◽

Umut Altunoglu ◽

Rebecca Miller ◽

Reza Maroofian ◽

Kiely N James ◽

...

Keyword(s):

Neurodevelopmental Disorder ◽

Critical Role ◽

Missense Variant ◽

Corneal Dystrophy ◽

Reproductive Organs ◽

Homozygosity Mapping ◽

Facial Dysmorphism ◽

Cerebellar Hypoplasia ◽

Loss Of Function

BackgroundPutative nucleotidyltransferase MAB21L1 is a member of an evolutionarily well-conserved family of the male abnormal 21 (MAB21)-like proteins. Little is known about the biochemical function of the protein; however, prior studies have shown essential roles for several aspects of embryonic development including the eye, midbrain, neural tube and reproductive organs.ObjectiveA homozygous truncating variant in MAB21L1 has recently been described in a male affected by intellectual disability, scrotal agenesis, ophthalmological anomalies, cerebellar hypoplasia and facial dysmorphism. We employed a combination of exome sequencing and homozygosity mapping to identify the underlying genetic cause in subjects with similar phenotypic features descending from five unrelated consanguineous families.ResultsWe identified four homozygous MAB21L1 loss of function variants (p.Glu281fs*20, p.Arg287Glufs*14 p.Tyr280* and p.Ser93Serfs*48) and one missense variant (p.Gln233Pro) in 10 affected individuals from 5 consanguineous families with a distinctive autosomal recessive neurodevelopmental syndrome. Cardinal features of this syndrome include a characteristic facial gestalt, corneal dystrophy, hairy nipples, underdeveloped labioscrotal folds and scrotum/scrotal agenesis as well as cerebellar hypoplasia with ataxia and variable microcephaly.ConclusionThis report defines an ultrarare but clinically recognisable Cerebello-Oculo-Facio-Genital syndrome associated with recessive MAB21L1 variants. Additionally, our findings further support the critical role of MAB21L1 in cerebellum, lens, genitalia and as craniofacial morphogenesis.

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An overview on the interplay between nutraceuticals and gut microbiota

PeerJ ◽

10.7717/peerj.4465 ◽

2018 ◽

Vol 6 ◽

pp. e4465 ◽

Cited By ~ 11

Author(s):

Adrian Catinean ◽

Maria Adriana Neag ◽

Dana Maria Muntean ◽

Ioana Corina Bocsan ◽

Anca Dana Buzoianu

Keyword(s):

Health Status ◽

Side Effects ◽

Alternative Therapy ◽

Animal Experiments ◽

Health Benefits ◽

Health Benefit ◽

Synthetic Drugs

BackgroundNowadays, growing attention was being given to the alternative ways to prevent or treat diseases. Nutraceuticals are used increasingly for this purpose. Many of these are being used as alternative therapy. Classic therapy with synthetic drugs, although very effective, has many side effects. The term “nutraceuticals” refers to the link between the nutritional and pharmaceutical domains. Also, lately, many studies have been done to investigate the role of microbiota in maintaining health. There is the hypothesis that some of the health benefits of nutraceuticals are due to their ability to change the microbiota. The aim of this review was to emphasize the link between the most commonly used nutraceuticals, the microbiota and the health benefits.MethodsWe selected the articles in PubMed, published up to July 2017, that provided information about most used nutraceuticals, microbiota and health benefits. In this review, we incorporate evidence from various types of studies, including observational,in vitroandin vivo, clinical studies or animal experiments.ResultsThe results demonstrate that many nutraceuticals change the composition of microbiota and can interfere with health status of the patients.DiscussionThere is evidence which sustains the importance of nutraceuticals in people’s health through microbiota but further studies are needed to complete the assessment of nutraceuticals in health benefit as a consequence of microbiota’s changing.

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Domain-Specific Response of Imprinted Genes to Reduced DNMT1

Molecular and Cellular Biology ◽

10.1128/mcb.01278-09 ◽

2010 ◽

Vol 30 (16) ◽

pp. 3916-3928 ◽

Cited By ~ 32

Author(s):

Jamie R. Weaver ◽

Garnik Sarkisian ◽

Christopher Krapp ◽

Jesse Mager ◽

Mellissa R. W. Mann ◽

...

Keyword(s):

Dna Methylation ◽

Dna Methyltransferase ◽

Critical Role ◽

Imprinted Genes ◽

Specific Response ◽

Loss Of Function ◽

Partial Loss ◽

Domain Specific ◽

Parent Of Origin

ABSTRACT Imprinted genes are expressed in a monoallelic, parent-of-origin-specific manner. Clusters of imprinted genes are regulated by imprinting control regions (ICRs) characterized by DNA methylation of one allele. This methylation is critical for imprinting; a reduction in the DNA methyltransferase DNMT1 causes a widespread loss of imprinting. To better understand the role of DNA methylation in the regulation of imprinting, we characterized the effects of Dnmt1 mutations on the expression of a panel of imprinted genes in the embryo and placenta. We found striking differences among imprinted domains. The Igf2 and Peg3 domains showed imprinting perturbations with both null and partial loss-of-function mutations, and both domains had pairs of coordinately regulated genes with opposite responses to loss of DNMT1 function, suggesting these domains employ similar regulatory mechanisms. Genes in the Kcnq1 domain were less sensitive to the absence of DNMT1. Cdkn1c exhibited imprinting perturbations only in null mutants, while Kcnq1 and Ascl2 were largely unaffected by a loss of DNMT1 function. These results emphasize the critical role for DNA methylation in imprinting and reveal the different ways it controls gene expression.

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