Current trends in the therapeutic strategies for diabetes management

Diabetes mellitus is one of the fastest-growing non-communicable diseases. Diabetes mellitus is caused due by the destruction of pancreatic β-cell or due to insulin resistance and characterized by hyperglycemia. Diabetes imposes a very serious economic crisis as the diabetic drug market is growing very rapidly. Even after very path-breaking scientific discoveries, the availability of better healthcare infrastructure, and a rise in literacy rates, the diabetes burden is continuously spreading in various sections all over the world but more especially in low- and middle-income countries. The recent developments in scientific discoveries have given several new generations of antidiabetic medicines such as sulphonylurea, biguanides, thiazolidinedione, α-glucosidase inhibitors. All these drugs have proved a significant reduction in blood glucose level. There are some new classes of hypoglycaemic drugs that have also been developed and reported, such as GLP-1 analogous, DPP-IV inhibitors, amylin inhibitors, and peroxisome proliferator-activated receptors. There are some active molecules and bioactive substances that have been purified from herbs and plants, which add value to the war against diabetes. These phytoconstituents have overturned drug development and lead identification for drugs against diabetes. The review also focuses on some critical areas of diabetes with more focus on statin-based diabetes management approach and stem cell therapy based next generation antidiabetic therapy

Molecular insights on the therapeutic effect of selected flavonoids on diabetic neuropathy

One of the common clinical complications of diabetes is diabetic neuropathy affecting the nervous system. Painful diabetic neuropathy is widespread and highly prevalent. At least 50% of diabetes patients eventually develop diabetic neuropathy. The four main types of diabetic neuropathy are peripheral neuropathy, autonomic neuropathy, proximal neuropathy (diabetic polyradiculopathy), and mononeuropathy (Focal neuropathy). Glucose control remains the common therapy for diabetic neuropathy due to limited knowledge on early biomarkers that are expressed during nerve damage, there-by limiting the cure through pharmacotherapy. Glucose control dramatically reduces the onset of neuropathy in type 1 diabetes but proves to be less effective in type 2 diabetes. Therefore, the focus is on various herbal remedies for prevention and treatment. There is numerous research on the use of anti-convulsants and antidepressants for the management of pain in diabetic neuropathy. Extensive research is being conducted on natural products, including the isolation of pure compounds like flavonoids from plants and their effect on diabetic neuropathy. This review focuses on the use of important flavonoids such as flavanols (e.g., quercetin, rutin, kaempferol, and isorhamnetin), flavanones (e.g., hesperidin, naringenin and class eriodictyol), and flavones (e.g., apigenin, luteolin, tangeretin, chrysin, and diosmin) for the prevention and treatment of diabetic neuropathy. The mechanisms of action of flavonoids against diabetic neuropathy by their antioxidant, anti-inflammation, anti-glycation proper-ties, etc., are also covered in this review article

Biofilm formed on UP and LIP surface (A) CFU, (B) carbohydrate and (C) protein (**p<0.001; *p<0.01).

<p>SEM images of (D) <i>S.aureus</i> adhered on UP and (E) LIP surfaces after 24 hr. AFM images of <i>E.coli</i> on (F) UP and (G) LIP.</p

Antibiofilm Properties of Silver and Gold Incorporated PU, PCLm, PC and PMMA Nanocomposites under Two Shear Conditions

<div><p>Silver and gold nanoparticles (of average size ∼20–27 nm) were incorporated in PU (Polyurethane), PCLm (Polycaprolactam), PC (polycarbonate) and PMMA (Polymethylmethaacrylate) by swelling and casting methods under ambient conditions. In the latter method the nanoparticle would be present not only on the surface, but also inside the polymer. These nanoparticles were prepared initially by using a cosolvent, THF. PU and PCLm were dissolved and swollen with THF. PC and PMMA were dissolved in CHCl₃ and here the cosolvent, THF, acted as an intermediate between water and CHCl₃. FTIR indicated that the interaction between the polymer and the nanoparticle was through the functional group in the polymer. The formation of <i>E.coli</i> biofilm on these nanocomposites under low (in a Drip flow biofilm reactor) and high shear (in a Shaker) conditions indicated that the biofilm growth was higher (twice) in the former than in the latter (ratio of shear force = 15). A positive correlation between the contact angle (of the virgin surface) and the number of colonies, carbohydrate and protein attached on it were observed. Ag nanocomposites exhibited better antibiofilm properties than Au. Bacterial attachment was highest on PC and least on PU nanocomposite. Casting method appeared to be better than swelling method in reducing the attachment (by a factor of 2). Composites reduced growth of organisms by six orders of magnitude, and protein and carbohydrate by 2–5 times. This study indicates that these nanocomposites may be suitable for implant applications.</p></div

Antibiofilm Properties of Interfacially Active Lipase Immobilized Porous Polycaprolactam Prepared by LB Technique

<div><p>Porous biomaterial is the preferred implant due to the interconnectivity of the pores. Chances of infection due to biofilm are also high in these biomaterials because of the presence of pores. Although biofilm in implants contributes to 80% of human infections <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096152#pone.0096152-Rmling1" target="_blank">[1]</a>, there are no commercially available natural therapeutics against it. In the current study, glutaraldehyde cross linked lipase was transferred onto a activated porous polycaprolactam surface using Langmuir-Blodgett deposition technique, and its thermostability, slimicidal, antibacterial, biocompatibility and surface properties were studied. There was a 20% increase in the activity of the covalently crosslinked lipase when compared to its free form. This immobilized surface was thermostable and retained activity and stability until 100°C. There was a 2 and 7 times reduction in carbohydrate and 9 and 5 times reduction in biofilm protein of <i>Staphylococcus aureus</i> and <i>Escherichia coli</i> respectively on lipase immobilized polycaprolactam (LIP) when compared to uncoated polycaprolactam (UP). The number of live bacterial colonies on LIP was four times less than on UP. Lipase acted on the cell wall of the bacteria leading to its death, which was confirmed from AFM, fluorescence microscopic images and amount of lactate dehydrogenase released. LIP allowed proliferation of more than 90% of 3T3 cells indicating that it was biocompatible. The fact that LIP exhibits antimicrobial property at the air-water interface to hydrophobic as well as hydrophilic bacteria along with lack of cytotoxicity makes it an ideal biomaterial for biofilm prevention in implants.</p></div

Changes in FTIR spectra of lipase immobilized on polycaprolactam (LIP) as a function of temperature.

<p>Changes in FTIR spectra of lipase immobilized on polycaprolactam (LIP) as a function of temperature.</p

Protein content of (A) <i>Acinetobacter</i> sp. and (B) <i>S</i>.<i>aureus</i> biofilms formed on bare, CC and PCC polymers after 24 hours of incubation (**p<0.01).

<p>Protein content of (A) <i>Acinetobacter</i> sp. and (B) <i>S</i>.<i>aureus</i> biofilms formed on bare, CC and PCC polymers after 24 hours of incubation (**p<0.01).</p

Design of a Papain Immobilized Antimicrobial Food Package with Curcumin as a Crosslinker

<div><p>Contamination of food products by spoilage and pathogenic microorganisms during post process handling is one of the major causes for food spoilage and food borne illnesses. The present green sustainable approach describes the covalent immobilization of papain to LDPE (low density polyethylene), HDPE (high density polyethylene), LLDPE (linear low density polyethylene) and PCL (polycaprolactam) with curcumin as the photocrosslinker. About 50% of curcumin and 82-92% of papain were successfully immobilized on these polymers. After 30 days, the free enzyme retained 87% of its original activity, while the immobilized enzyme retained more than 90% of its activity on these polymers. Papain crosslinked to LLDPE exhibited the best antibiofilm properties against <i>Acinetobacter</i> sp. KC119137.1 and <i>Staphylococcus aureus</i> NCIM 5021 when compared to the other three polymers, because of the highest amount of enzyme immobilized on this surface. Papain acts by damaging the cell membrane. The enzyme is able to reduce the amount of carbohydrate and protein contents in the biofilms formed by these organisms. Meat wrapped with the modified LDPE and stored at 4°C showed 9 log reduction of these organisms at the end of the seventh day when compared to samples wrapped with the bare polymer. This method of crosslinking can be used on polymers with or without functional groups and can be adopted to bind any type of antimicrobial agent.</p></div

Fluorescence microscopic images of <i>E.coli</i> and <i>S.aureus</i> formed on UP (A & C) and LIP (B & D) surfaces respectively after 24 h of incubation.

<p>Green dots represent live and red colour represents dead cells.</p

Population (Log CFU/cm²) of (A) <i>Acinetobacter</i> sp. and (B) <i>S</i>.<i>aureus</i> biofilms formed on bare, CC and PCC polymers after 24 hours of incubation (*p<0.5,***p<0.001).

<p>Population (Log CFU/cm²) of (A) <i>Acinetobacter</i> sp. and (B) <i>S</i>.<i>aureus</i> biofilms formed on bare, CC and PCC polymers after 24 hours of incubation (*p<0.5,***p<0.001).</p