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  1. Article: DNA methylation in the pathogenesis of type 2 diabetes.

    Kaimala, Suneesh / Ansari, Suraiya Anjum / Emerald, Bright Starling

    Vitamins and hormones

    2022  Volume 122, Page(s) 147–169

    Abstract: Type 2 diabetes (T2D) is a metabolic disease characterized by the development of β-cell dysfunction with hepatic, muscular and adipose tissue insulin resistance. Although the molecular mechanisms leading to its development are not entirely known, ... ...

    Abstract Type 2 diabetes (T2D) is a metabolic disease characterized by the development of β-cell dysfunction with hepatic, muscular and adipose tissue insulin resistance. Although the molecular mechanisms leading to its development are not entirely known, investigations of its causes reveal a multifactorial contribution to its development and progression in most cases. In addition, regulatory interactions mediated by epigenetic modifications such as DNA methylation, histone tail modifications and regulatory RNAs have been found to play a significant role in the etiology of T2D. In this chapter, we discuss the role of DNA methylation and its dynamics in the development of the pathological features of T2D.
    MeSH term(s) Humans ; DNA Methylation ; Diabetes Mellitus, Type 2/genetics ; Epigenesis, Genetic ; Adipose Tissue
    Language English
    Publishing date 2022-12-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 201161-x
    ISSN 2162-2620 ; 0083-6729
    ISSN (online) 2162-2620
    ISSN 0083-6729
    DOI 10.1016/bs.vh.2022.11.002
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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.238: Show issues Location:
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  2. Article ; Online: A pilot study: effect of irisin on trabecular bone in a streptozotocin-induced animal model of type 1 diabetic osteopathy utilizing a micro-CT.

    Mohsin, Sahar / Brock, Fiona / Kaimala, Suneesh / Greenwood, Charlene / Sulaiman, Mohsin / Rogers, Keith / Adeghate, Ernest

    PeerJ

    2023  Volume 11, Page(s) e16278

    Abstract: Background: Osteoporosis is a significant co-morbidity of type 1 diabetes mellitus (DM1) leading to increased fracture risk. Exercise-induced hormone 'irisin' in low dosage has been shown to have a beneficial effect on bone metabolism by increasing ... ...

    Abstract Background: Osteoporosis is a significant co-morbidity of type 1 diabetes mellitus (DM1) leading to increased fracture risk. Exercise-induced hormone 'irisin' in low dosage has been shown to have a beneficial effect on bone metabolism by increasing osteoblast differentiation and reducing osteoclast maturation, and inhibiting apoptosis and inflammation. We investigated the role of irisin in treating diabetic osteopathy by observing its effect on trabecular bone.
    Methods: DM1 was induced by intraperitoneal injection of streptozotocin 60 mg/kg body weight. Irisin in low dosage (5 µg twice a week for 6 weeks I/P) was injected into half of the control and 4-week diabetic male Wistar rats. Animals were sacrificed six months after induction of diabetes. The trabecular bone in the femoral head and neck was analyzed using a micro-CT technique. Bone turnover markers were measured using ELISA, Western blot, and RT-PCR techniques.
    Results: It was found that DM1 deteriorates the trabecular bone microstructure by increasing trabecular separation (Tb-Sp) and decreasing trabecular thickness (Tb-Th), bone volume fraction (BV/TV), and bone mineral density (BMD). Irisin treatment positively affects bone quality by increasing trabecular number
    Conclusions: This is the first pilot study to our knowledge that shows that a low dose of irisin marginally improves the trabecular bone in DM1 and is an effective peptide in reducing sclerostin levels.
    MeSH term(s) Rats ; Animals ; Male ; X-Ray Microtomography ; Fibronectins ; Pilot Projects ; Streptozocin ; Osteocalcin ; Diabetes Mellitus, Type 1/drug therapy ; Cancellous Bone/diagnostic imaging ; Rats, Wistar ; Models, Animal
    Chemical Substances Fibronectins ; Streptozocin (5W494URQ81) ; Osteocalcin (104982-03-8)
    Language English
    Publishing date 2023-10-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2703241-3
    ISSN 2167-8359 ; 2167-8359
    ISSN (online) 2167-8359
    ISSN 2167-8359
    DOI 10.7717/peerj.16278
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  3. Article ; Online: Epigenetic modifications in pancreas development, diabetes, and therapeutics.

    Kaimala, Suneesh / Kumar, Challagandla Anil / Allouh, Mohammed Z / Ansari, Suraiya Anjum / Emerald, Bright Starling

    Medicinal research reviews

    2022  Volume 42, Issue 3, Page(s) 1343–1371

    Abstract: A recent International Diabetes Federation report suggests that more than 463 million people between 20 and 79 years have diabetes. Of the 20 million women affected by hyperglycemia during pregnancy, 84% have gestational diabetes. In addition, more than ... ...

    Abstract A recent International Diabetes Federation report suggests that more than 463 million people between 20 and 79 years have diabetes. Of the 20 million women affected by hyperglycemia during pregnancy, 84% have gestational diabetes. In addition, more than 1.1 million children or adolescents are affected by type 1 diabetes. Factors contributing to the increase in diabetes prevalence are complex and include contributions from genetic, environmental, and epigenetic factors. However, molecular regulatory mechanisms influencing the progression of an individual towards increased susceptibility to metabolic diseases such as diabetes are not fully understood. Recent studies suggest that the pathogenesis of diabetes involves epigenetic changes, resulting in a persistently dysregulated metabolic phenotype. This review summarizes the role of epigenetic mechanisms, mainly DNA methylation and histone modifications, in the development of the pancreas, their contribution to the development of diabetes, and the potential employment of epigenetic modulators in diabetes treatment.
    MeSH term(s) Adolescent ; DNA Methylation/genetics ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/therapy ; Epigenesis, Genetic ; Female ; Humans ; Pancreas ; Phenotype ; Pregnancy
    Language English
    Publishing date 2022-01-04
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 603210-2
    ISSN 1098-1128 ; 0198-6325
    ISSN (online) 1098-1128
    ISSN 0198-6325
    DOI 10.1002/med.21878
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1764: Show issues Location:
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  4. Article ; Online: An evolutionarily conserved non-coding element in casein locus acts as transcriptional repressor.

    Kaimala, Suneesh / Kumar, Satish

    Gene

    2015  Volume 554, Issue 1, Page(s) 75–80

    Abstract: In mammals, the casein locus consists of stretches of non-coding DNA, the functions of most of which are unknown. These regions are believed to harbour elements responsible for spatio-temporally regulated expression of genes in this locus and so far, ... ...

    Abstract In mammals, the casein locus consists of stretches of non-coding DNA, the functions of most of which are unknown. These regions are believed to harbour elements responsible for spatio-temporally regulated expression of genes in this locus and so far, only a few such elements have been identified. In this study, we report a novel regulatory element in the casein locus. Comparative analysis of genomic DNA sequences of casein loci from different mammals identified a 147bp long evolutionarily conserved region (ECR) upstream of Odam, a gene in this locus. The ECR was found in close proximity of Odam gene in all the mammals examined. In-silico analysis predicted the ECR as a potential regulatory element. Functional analysis in different cell lines identified it as a unidirectional repressor element. From our findings we speculate that the ECR may be involved in the repression of the Odam expression in the mammary gland during lactation.
    MeSH term(s) Animals ; Binding Sites ; Caseins/genetics ; Cattle ; Cell Line ; Conserved Sequence ; Evolution, Molecular ; Female ; Gene Expression Regulation ; Humans ; Mammary Glands, Animal/metabolism ; Mice ; Promoter Regions, Genetic ; Rats ; Regulatory Sequences, Nucleic Acid ; Species Specificity ; Transcription Factors/metabolism ; Transcription, Genetic
    Chemical Substances Caseins ; Transcription Factors
    Language English
    Publishing date 2015-01-01
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 391792-7
    ISSN 1879-0038 ; 0378-1119
    ISSN (online) 1879-0038
    ISSN 0378-1119
    DOI 10.1016/j.gene.2014.10.026
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1357: Show issues Location:
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  5. Article: An evolutionarily conserved non-coding element in casein locus acts as transcriptional repressor

    Kaimala, Suneesh / Satish Kumar

    Gene. 2015 Jan. 01, v. 554

    2015  

    Abstract: In mammals, the casein locus consists of stretches of non-coding DNA, the functions of most of which are unknown. These regions are believed to harbour elements responsible for spatio-temporally regulated expression of genes in this locus and so far, ... ...

    Abstract In mammals, the casein locus consists of stretches of non-coding DNA, the functions of most of which are unknown. These regions are believed to harbour elements responsible for spatio-temporally regulated expression of genes in this locus and so far, only a few such elements have been identified. In this study, we report a novel regulatory element in the casein locus. Comparative analysis of genomic DNA sequences of casein loci from different mammals identified a 147bp long evolutionarily conserved region (ECR) upstream of Odam, a gene in this locus. The ECR was found in close proximity of Odam gene in all the mammals examined. In-silico analysis predicted the ECR as a potential regulatory element. Functional analysis in different cell lines identified it as a unidirectional repressor element. From our findings we speculate that the ECR may be involved in the repression of the Odam expression in the mammary gland during lactation.
    Keywords casein ; gene expression ; genes ; genomics ; intergenic DNA ; lactation ; loci ; mammals ; mammary glands ; nucleotide sequences ; repressor proteins
    Language English
    Dates of publication 2015-0101
    Size p. 75-80.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 391792-7
    ISSN 1879-0038 ; 0378-1119
    ISSN (online) 1879-0038
    ISSN 0378-1119
    DOI 10.1016/j.gene.2014.10.026
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    In stock of ZB MED Bonn / Germany

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  6. Article ; Online: In vivo Labeling of Bone Microdamage in an Animal Model of Type 1 Diabetes Mellitus.

    Mohsin, Sahar / Kaimala, Suneesh / AlTamimi, Eman Khamis Yousef / Tariq, Saeed / Adeghate, Ernest

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 16994

    Abstract: Type 1 diabetes mellitus (DM1) is linked to a decrease in bone strength. Bone strength entails both bone mineral density and bone quality. Limited data are available regarding diabetes-induced microdamage, which can severely influence bone quality. This ... ...

    Abstract Type 1 diabetes mellitus (DM1) is linked to a decrease in bone strength. Bone strength entails both bone mineral density and bone quality. Limited data are available regarding diabetes-induced microdamage, which can severely influence bone quality. This study has investigated bone microdamage as a measure of bone quality in an animal model of DM1. Microdamage in the neck of the femur was labelled in vivo using multiple fluorochromes at 4, 12 and 24 weeks after the onset of DM1. Microcracks were quantified and their morphology analyzed using microscopy techniques. The mean length of microcracks at 24 weeks, and crack numerical and surface densities were significantly higher (p < 0.05) 4 weeks after the onset of DM1 when compared with control. Diffuse damage density was highest at 12 weeks after the onset of DM1. The arrangement of the collagen fibrils became progressively more irregular from 4 to 24 weeks of DM. This is the first study to analyze microdamage in vivo at different time points of DM1. DM1is associated with microcracks from the early stage, however bone microstructure shows toughening mechanisms that arrest their growth but disease progression further deteriorates bone quality resulting in longer microcracks which may increase fracture risk.
    MeSH term(s) Animals ; Bone Density ; Bone and Bones/metabolism ; Bone and Bones/physiopathology ; Bone and Bones/ultrastructure ; Compressive Strength ; Diabetes Mellitus, Experimental/physiopathology ; Diabetes Mellitus, Type 1/physiopathology ; Disease Models, Animal ; Fluorescent Dyes/metabolism ; Fractures, Bone/diagnosis ; Fractures, Bone/metabolism ; Fractures, Bone/physiopathology ; Male ; Microscopy, Confocal ; Microscopy, Electron, Transmission ; Rats, Wistar ; Stress, Mechanical ; Time Factors
    Chemical Substances Fluorescent Dyes
    Language English
    Publishing date 2019-11-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-53487-6
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  7. Article ; Online: Type 2 Diabetes Mellitus Increases the Risk to Hip Fracture in Postmenopausal Osteoporosis by Deteriorating the Trabecular Bone Microarchitecture and Bone Mass.

    Mohsin, Sahar / Kaimala, Suneesh / Sunny, Jens Jolly / Adeghate, Ernest / Brown, Eric Mensah

    Journal of diabetes research

    2019  Volume 2019, Page(s) 3876957

    Abstract: T2DM is linked to an increase in the fracture rate as compared to the nondiabetic population even with normal or raised bone mineral density (BMD). Hence, bone quality plays an important role in the pathogenesis of skeletal fragility due to T2DM. This ... ...

    Abstract T2DM is linked to an increase in the fracture rate as compared to the nondiabetic population even with normal or raised bone mineral density (BMD). Hence, bone quality plays an important role in the pathogenesis of skeletal fragility due to T2DM. This study analyzed the changes in the trabecular bone microstructure due to T2DM at various time points in ovariectomized and nonovariectomized rats. Animals were divided into four groups: (I) control (sham), (II) diabetic (sham), (III) ovariectomized, and (IV) ovariectomized with diabetes. The trabecular microarchitecture of the femoral head was characterized using a micro-CT. The differences between the groups were analyzed at 8, 10, and 14 weeks of the onset of T2DM using a two-way analysis of variance and by post hoc multiple comparisons. The diabetic group with and without ovariectomies demonstrated a significant increase in trabecular separation and a decrease in bone volume fraction, trabecular number, and thickness. BMD decreased in ovariectomized diabetic animals at 14 weeks of the onset of T2DM. No significant change was found in connectivity density and degree of anisotropy among groups. The structural model index suggested a change towards a weaker rod-like microstructure in diabetic animals. The data obtained suggested that T2DM affects the trabecular structure within a rat's femoral heads negatively and changes are most significant at a longer duration of T2DM, increasing the risk to hip fractures.
    MeSH term(s) Animals ; Bone Density ; Cancellous Bone/diagnostic imaging ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Type 2/epidemiology ; Diabetes Mellitus, Type 2/metabolism ; Female ; Femur Head/diagnostic imaging ; Hip Fractures/epidemiology ; Humans ; Osteoporosis/diagnostic imaging ; Osteoporosis, Postmenopausal/epidemiology ; Osteoporotic Fractures/epidemiology ; Ovariectomy ; Postmenopause ; Rats ; Risk Factors ; X-Ray Microtomography
    Language English
    Publishing date 2019-11-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 2711897-6
    ISSN 2314-6753 ; 2314-6745
    ISSN (online) 2314-6753
    ISSN 2314-6745
    DOI 10.1155/2019/3876957
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  8. Article ; Online: Mammary gland stem cells: more puzzles than explanations.

    Kaimala, Suneesh / Bisana, Swathi / Kumar, Satish

    Journal of biosciences

    2012  Volume 37, Issue 2, Page(s) 349–358

    Abstract: Mammary gland stem cells (MaSC) have not been identified in spite of extensive research spanning over several decades. This has been primarily due to the complexity of mammary gland structure and its development, cell heterogeneity in the mammary gland ... ...

    Abstract Mammary gland stem cells (MaSC) have not been identified in spite of extensive research spanning over several decades. This has been primarily due to the complexity of mammary gland structure and its development, cell heterogeneity in the mammary gland and the insufficient knowledge about MaSC markers. At present, Lin (-) CD29 (i) CD49f (i) CD24 (+/mod) Sca- 1 (-) cells of the mammary gland have been reported to be enriched with MaSCs. We suggest that the inclusion of stem cell markers like Oct4, Sox2, Nanog and the mammary gland differentiation marker BRCA-1 may further narrow down the search for MaSCs. In addition, we have discussed some of the other unresolved puzzles on the mammary gland stem cells, such as their similarities and/or differences with mammary cancer stem cells, use of milk as source of mammary stem cells and the possibility of in vitro differentiation of embryonic stem (ES) cells into functional mammary gland structures in this review. Nevertheless, it is the lack of identity for a MaSC that is curtailing the advances in some of the above and other related areas.
    MeSH term(s) Animals ; Cell Differentiation/physiology ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Female ; Humans ; Mammary Glands, Animal/cytology ; Mammary Glands, Animal/metabolism ; Mammary Glands, Human/cytology ; Mammary Glands, Human/metabolism ; Mice ; Neoplastic Stem Cells/cytology ; Neoplastic Stem Cells/metabolism ; Stem Cells/cytology ; Stem Cells/metabolism
    Language English
    Publishing date 2012-05-13
    Publishing country India
    Document type Journal Article ; Review
    ZDB-ID 756157-x
    ISSN 0973-7138 ; 0250-5991
    ISSN (online) 0973-7138
    ISSN 0250-5991
    DOI 10.1007/s12038-012-9200-z
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1907: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  9. Article: Mammary gland stem cells: More puzzles than explanations

    Kaimala, Suneesh / Bisana, Swathi / Kumar, Satish

    Journal of biosciences. 2012 June, v. 37, no. 2

    2012  

    Abstract: Mammary gland stem cells (MaSC) have not been identified in spite of extensive research spanning over several decades. This has been primarily due to the complexity of mammary gland structure and its development, cell heterogeneity in the mammary gland ... ...

    Abstract Mammary gland stem cells (MaSC) have not been identified in spite of extensive research spanning over several decades. This has been primarily due to the complexity of mammary gland structure and its development, cell heterogeneity in the mammary gland and the insufficient knowledge about MaSC markers. At present, Lin–CD29hiCD49fhiCD24+/modSca-1– cells of the mammary gland have been reported to be enriched with MaSCs. We suggest that the inclusion of stem cell markers like Oct4, Sox2, Nanog and the mammary gland differentiation marker BRCA-1 may further narrow down the search for MaSCs. In addition, we have discussed some of the other unresolved puzzles on the mammary gland stem cells, such as their similarities and/or differences with mammary cancer stem cells, use of milk as source of mammary stem cells and the possibility of in vitro differentiation of embryonic stem (ES) cells into functional mammary gland structures in this review. Nevertheless, it is the lack of identity for a MaSC that is curtailing the advances in some of the above and other related areas.
    Keywords cell differentiation ; mammary glands ; milk ; neoplasms ; stem cells
    Language English
    Dates of publication 2012-06
    Size p. 349-358.
    Publishing place Springer-Verlag
    Document type Article
    ZDB-ID 756157-x
    ISSN 0973-7138 ; 0250-5991
    ISSN (online) 0973-7138
    ISSN 0250-5991
    DOI 10.1007/s12038-012-9200-z
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  10. Article: Attenuated Bacteria as Immunotherapeutic Tools for Cancer Treatment.

    Kaimala, Suneesh / Al-Sbiei, Ashraf / Cabral-Marques, Otavio / Fernandez-Cabezudo, Maria J / Al-Ramadi, Basel K

    Frontiers in oncology

    2018  Volume 8, Page(s) 136

    Abstract: The use of attenuated bacteria as cancer therapeutic tools has garnered increasing scientific interest over the past 10 years. This is largely due to the development of bacterial strains that maintain good anti-tumor efficacy, but with reduced potential ... ...

    Abstract The use of attenuated bacteria as cancer therapeutic tools has garnered increasing scientific interest over the past 10 years. This is largely due to the development of bacterial strains that maintain good anti-tumor efficacy, but with reduced potential to cause toxicities to the host. Because of its ability to replicate in viable as well as necrotic tissue, cancer therapy using attenuated strains of facultative anaerobic bacteria, such as
    Language English
    Publishing date 2018-05-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2018.00136
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