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Diabetes risk assessment among squatter settlements in Pakistan: A cross-sectional study

Ishaque A, Shahzad F, Muhammad FH, Usman Y, Ishaque Z

Malays Fam Physician, 2016;11(2-3):9-15.
PMID: 28461852

INTRODUCTION: Diabetes mellitus (DM) has evolved as a major public health concern worldwide, as its prevalence is increasing exponentially. Pakistan now ranks seventh among the countries with the highest burden of DM. It is expected to become one of the major causes of morbidity within the next 25 years. Therefore, finding an effective way to identify individuals at risk of developing diabetes is a necessity. The Finnish Diabetes Risk Score (FINDRISC) has proved to be an effective noninvasive screening tool for identifying individuals at risk for developing diabetes. The objective of this study was to determine the frequency of individuals who are at risk for developing DM and their risk of developing DM over the next 10 years using the FINDRISC tool.
METHODS: A cross-sectional survey was conducted on 241 adults. The data were collected using the FINDRISC questionnaire followed by calculation of a summated score and analysis to determine the association between the risk factors under study and the risk of developing diabetes.
RESULTS: Out of 241 study participants, 137 (56.8%) were men and 104 (43.1%) were women. Our study showed that 129 (53.5%) participants had low risk, 68 (28.2%) had slightly elevated risk, 27 (11.2%) had moderate risk and 17 (7%) had high risk of developing DM.
CONCLUSION: The general population should be educated about the importance of healthy lifestyle, with special emphases on maintaining an ideal body mass index and a low-risk waist circumference, along with daily fruit and vegetable intake and physical activity of at least 30 min/day.
Alpha terpineol directs bone marrow mesenchymal stem cells toward neuronal lineage through regulation of wnt signaling pathway

Ishaque A, Salim A, Simjee SU, Khan I, Adli DSH

Cell Biochem Funct, 2023 Mar;41(2):223-233.
PMID: 36651266 DOI: 10.1002/cbf.3775

Central nervous system anomalies give rise to neuropathological consequences with immense damage to the neuronal tissues. Cell based therapeutics have the potential to manage several neuropathologies whereby the differentiated cells are explored for neuronal regeneration. The current study analyzes the effect of a bioactive compound, alpha terpineol (AT) on the differentiation of rat bone marrow derived mesenchymal stem cells (BM-MSCs) toward neuronal lineage, and explores regulation of differentiation process through the study of Wnt pathway mediators. BM-MSCs were cultured and characterized based on their surface markers and tri-lineage differentiation. Safe dose of AT as optimized by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium bromide assay, was used for the treatment of MSCs. Treated cells were analyzed for the neuronal, astroglial and germ layer transition markers at the gene and protein levels, by quantitative polymerase chain reaction and immunocytochemistry, respectively. Temporal expression of Wnt pathway genes was assessed during the course of neuronal differentiation. AT treated group showed significant upregulation of neuron specific (NSE, MAP2, Tau, Nestin, and NefL) and astroglial (GFAP) genes with positive expression of late neuronal markers. Germ layer transition analysis showed the overexpression of ectodermal markers (NCAM, Nestin, and Pax6), whereas endodermal (AFP, MixL1, and Sox17), and mesodermal (Mesp1 and T Brachyury) markers were also found to be upregulated. Wnt signaling pathway was activated during the initial phase (30 min) of differentiation, which later was downregulated at 1, 3, and 5 h. AT efficiently induces neuronal differentiation of BM-MSCs by regulating Wnt signaling. Overexpression of both early and late neuronal markers indicate their neuro-progenitor state and thus can be utilized as a promising approach in cellular therapeutics to treat various neurodegenerative ailments. In addition, exploration of the molecular pathways may be helpful to understand the mechanism of cell-based neuronal regeneration.
Effect of lawsone-preconditioned mesenchymal stem cells on the regeneration of pancreatic β cells in Type 1 diabetic rats

Masnoon J, Ishaque A, Khan I, Salim A, Kabir N

Cell Biochem Funct, 2023 Oct;41(7):833-844.
PMID: 37814478 DOI: 10.1002/cbf.3833

Diabetes is one of the major health issues globally. Type 1 diabetes mellitus develops due to the destruction of pancreatic β cells. Mesenchymal stem cells (MSCs) having remarkable self-renewal and differentiation potential, can regenerate β cells. MSCs preconditioned with bioactive small molecules possess enhanced biological features and therapeutic potential under in vivo environment. Interestingly, compounds of naphthoquinone class possess antidiabetic and anti-inflammatory properties, and can be explored as potential candidates for preconditioning MSCs. This study analyzed the effect of lawsone-preconditioned human umbilical cord MSCs (hUMSCs) on the regeneration of β cells in the streptozotocin (STZ)-induced Type 1 diabetes (T1D) rats. hUMSCs were isolated and characterized for the presence of surface markers. MSCs were preconditioned with optimized concentration of lawsone. T1D rat model was established by injecting 50 mg/kg of STZ intraperitoneally. Untreated and lawsone-preconditioned hUMSCs were transplanted into the diabetic rats via tail vein. Fasting blood sugar and body weight were monitored regularly for 4 weeks. Pancreas was harvested and β cell regeneration was evaluated by hematoxylin and eosin staining, and gene expression analysis. Immunohistochemistry was also done to assess the insulin expression. Lawsone-preconditioned hUMSCs showed better anti-hyperglycemic effect in comparison with untreated hUMSCs. Histological analysis presented the regeneration of islets of Langerhans with upregulated expression of βcell genes and reduced expression of inflammatory markers. Immunohistochemistry revealed strong insulin expression in the preconditioned hUMSCs compared with the untreated hUMSCs. It is concluded from the present study that lawsone-preconditioned hMSCs were able to exhibit pronounced anti-hyperglycemic effect in vivo compared with hUMSCs alone.
Fulltext Overexpression of OLIG2 and MYT1L Transcription Factors Enhance the Differentiation Potential of Human Mesenchymal Stem Cells into Oligodendrocytes

Fahim I, Ishaque A, Ramzan F, Shamsuddin SABA, Ali A, Salim A, et al.

Curr Issues Mol Biol, 2023 May 07;45(5):4100-4123.
PMID: 37232730 DOI: 10.3390/cimb45050261

BACKGROUND: Demyelinating diseases represent a broad spectrum of disorders and are characterized by the loss of specialized glial cells (oligodendrocytes), which eventually leads to neuronal degeneration. Stem cell-based regenerative approaches provide therapeutic options to regenerate demyelination-induced neurodegeneration.
OBJECTIVES: The current study aims to explore the role of oligodendrocyte-specific transcription factors (OLIG2 and MYT1L) under suitable media composition to facilitate human umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) differentiation toward oligodendrocyte for their potential use to treat demyelinating disorders.
METHODOLOGY: hUC-MSCs were isolated, cultured, and characterized based on their morphological and phenotypic characteristics. hUC-MSCs were transfected with OLIG2 and MYT1L transcription factors individually and in synergistic (OLIG2 + MYT1L) groups using a lipofectamine-based transfection method and incubated under two different media compositions (normal and oligo induction media). Transfected hUC-MSCs were assessed for lineage specification and differentiation using qPCR. Differentiation was also analyzed via immunocytochemistry by determining the expression of oligodendrocyte-specific proteins.
RESULTS: All the transfected groups showed significant upregulation of GFAP and OLIG2 with downregulation of NES, demonstrating the MSC commitment toward the glial lineage. Transfected groups also presented significant overexpression of oligodendrocyte-specific markers (SOX10, NKX2.2, GALC, CNP, CSPG4, MBP, and PLP1). Immunocytochemical analysis showed intense expression of OLIG2, MYT1L, and NG2 proteins in both normal and oligo induction media after 3 and 7 days.
CONCLUSIONS: The study concludes that OLIG2 and MYT1L have the potential to differentiate hUC-MSCs into oligodendrocyte-like cells, which is greatly facilitated by the oligo induction medium. The study may serve as a promising cell-based therapeutic strategy against demyelination-induced neuronal degeneration.