Type 2 diabetic neuropathy with special reference to mitochondrial role and its effective management

Diabetic neuropathy denotes to a group of nerve disorders caused by diabetes. It may occur in both type 1 and type 2 diabetes patients. Mitochondria are essential for energy production as well as intermediary metabolism and equally important in the action of insulin on its targeted tissue. Recently, mitochondrial dysfunctions have been recognized as a cause of diabetes. Hyperglycemia enhances the activity of mitochondrial electron transport chain, leading to mitochondrial hyperpolarisation and elevates the reactive oxygen species (ROS) production. Increased electron availability causes partial reduction of oxygen to superoxide in the proximal electron transport chain which subsequently induces neurodegeneration in diabetes. Currently there is no satisfactory pharmacotherapy for painful diabetic neuropathy. This review summarizes mitochondrial role in type 2 diabetic neuropathy, diagnostic challenges, general treatments and benefits of alternative approach for effective management

Structural, Morphological and Optical Properties of Perfume Atomizer Spray Pyrolysis CdO Thin Films: Effect of Solution Volume

CdO films have been deposited on glass substrates with different solution volume (30, 40 and 50 mL) at 200°C using perfume atomizers spray pyrolysis method. X-ray diffraction studies shows that the prepared thin film had cubic and polycrystalline nature. Scanning electron microscope shows the influence of solution volume on surface morphology of the CdO thin film. Optical studies show that in these films the electronic transition is of the direct transition type. The optical energy gap for the films of as deposited are vary from 2.12 to 2.00 eV with solution volume. Photoluminescence results analysis confirmed that the dependence of optical energy gap on solution volume. The Hall measurements were carried out and the results were discussed

A cell-surface autoantibody targets zinc transporter-8 (ZnT8) for in vivo B-cell imaging and islet-specific therapies

Type 1 diabetes (T1D) is a disease in which autoimmune attack is directed to the insulin-producing b-cell in the pancreatic islet. Autoantigens on the b-cell surface membrane are specific markers for molecular recognition and targets for engagement by autoreactive B lymphocytes, which produce islet cell surface autoantibody (ICSA) upon activation. Here, we report the cloning of an ICSA (mAb43) that recognizes a major T1D autoantigen, ZnT8, with a subnanomolar binding affinity and conformation specificity. We demonstrate that cell-surface binding of mAb43 protects the extracellular epitope of ZnT8 against immunolabeling by serum ICSA from a patient with T1D. Further, mAb43 exhibits in vitro and ex vivo specificity for islet cells, mirroring the exquisite specificity of islet autoimmunity in T1D. Systemic administration of mAb43 yields a pancreas-specific biodistribution in mice and islet homing of a mAb43-linked imaging payload through the pancreatic vasculature, thereby validating the in vivo specificity of mAb43. Identifying ZnT8 as a major antigenic target of ICSA allows for research into the molecular recognition and engagement of autoreactive B cells in the chronic phase of T1D progression. The in vivo islet specificity of mAb43 could be further exploited to develop in vivo imaging and islet-specific immunotherapies.</p

Cell-surface ZnT8 antibody prevents and reverses autoimmune diabetes in mice

Type 1 diabetes (T1D) is an autoimmune disease where pathogenic lymphocytes target autoantigens expressed in the pancreatic islets, leading to the destruction of insulin-producing β-cells. Zinc transporter 8 (ZnT8) is a major autoantigen abundantly present on the β-cell surface. This unique molecular target offers the potential to shield β-cells against autoimmune attacks in T1D. Our previous work showed that a monoclonal antibody (mAb43) against cell-surface ZnT8 can home in on the pancreatic islets and prevent autoantibodies from recognizing β-cells. This study demonstrates that mAb43 binds to exocytotic sites on the β-cell surface, masking the antigenic exposure of ZnT8 and insulin following glucose-stimulated insulin secretion. In vivo administration of mAb43 to nonobese diabetic (NOD) mice selectively increased the proportion of regulatory T-cells (Tregs) in the islet, resulting in complete and sustained protection against T1D onset as well as reversal of new-onset diabetes. The mAb43-induced self-tolerance was reversible after treatment cessation and exhibited no adverse effects during long-term monitoring. Our findings suggest that mAb43 masking of the antigenic exposure of β-cells suppresses the immunological cascade from B-cell antigen presentation to T-cell mediated β-cell destruction, providing a novel islet-targeted and antigen-specific immunotherapy to prevent and reverse clinical T1D.</p

Ocimum sanctum Linn. A reservoir plant for therapeutic applications: An overview

The medicinal plants are widely used by the traditional medicinal practitioners for curing various diseases in their day to day practice. In traditional system of medicine, different parts (leaves, stem, flower, root, seeds and even whole plant) of Ocimum sanctum Linn. have been recommended for the treatment of bronchitis, malaria, diarrhea, dysentery, skin disease, arthritis, eye diseases, insect bites and so on. The O. sanctum L. has also been suggested to possess anti-fertility, anticancer, antidiabetic, antifungal, antimicrobial, cardioprotective, analgesic, antispasmodic and adaptogenic actions. Eugenol (1-hydroxy-2-methoxy-4-allylbenzene), the active constituents present in O. sanctum L. have been found to be largely responsible for the therapeutic potentials. The pharmacological studies reported in the present review confirm the therapeutic value of O. sanctum L. The results of the above studies support the use of this plant for human and animal disease therapy and reinforce the importance of the ethno-botanical approach as a potential source of bioactive substances