Engineered islet cell clusters transplanted into subcutaneous space are superior to pancreatic islets in diabetes

Pathak, Shiva,Regmi, Shobha,Gupta, Biki,Pham, Tung Thanh,Yong, Chul Soon,Kim, Jong Oh,Yook, Simmyung,Kim, Jae-Ryong,Park, Min Hui,Bae, Young Kyung,Jeong, Jee-Heon Federation of American Societies for Experimental 2017 The FASEB Journal Vol. No.

<P>An alternative route for pancreatic islet transplantation is the subcutaneous space; however, inadequate vascularization in the subcutaneous space limits the availability of oxygen and nutrients to the subcutaneously transplanted islets, which leads to the development of a necrotic core in the islets, thereby causing islet dysfunction. Thus, we aimed to prevent the early apoptosis of pancreatic islets after transplantation into subcutaneous space by preparing islet clusters of appropriate size. We prepared fully functional islet cell clusters (ICCs) by using the hanging-drop technique. We optimized the size of ICCs on the basis of viability and functionality after culture in an hypoxic environment. We transplanted ICCs into the subcutaneous space of diabetic mice and evaluated the viability of the islets at the transplantation site. In an hypoxic environment, ICCs exhibited improved viability and functionality compared with control islets. ICCs, upon transplantation into the hypoxic subcutaneous space of diabetic mice, showed better glycemic control compared with control islets. Live/dead imaging of the islets after retrieval fromthe transplanted area revealed significantly reduced apoptosis in ICCs. Transplantation of ICCsmay be an attractive strategy to prevent islet cell apoptosis that results from nonimmune-mediated physiologic stress at the transplantation site.-Pathak, S., Regmi, S., Gupta, B., Pham, T. T., Yong, C. S., Kim, J. O., Yook, S., Kim, J.-R., Park, M. H., Bae, Y. K., Jeong, J.-H. Engineeredislet cell clusters transplanted into subcutaneous space are superior to pancreatic islets in diabetes.</P>

Narrowband ultraviolet B emission from gadolinium activated Y₃Ga₅O₁₂ nano-garnets

Pathak, M.S.,Singh, N.,Singh, Vijay,Watanabe, S.,Rao, T.K.Gundu,Lee, Jung-Kul Elsevier 2018 Materials research bulletin Vol.97 No.-

<P><B>Abstract</B></P> <P>Gadolinium (Gd<SUP>3+</SUP>) doped Y<SUB>3</SUB>Ga<SUB>5</SUB>O<SUB>12</SUB> nanocrystalline garnet was prepared by nitrate-fuel combustion technique that involves organic fuel glycine. Sample characterization was performed by powder X-ray diffraction and scanning electron microscope. Upon ultraviolet light excitation at 273nm, Y<SUB>3</SUB>Ga<SUB>5</SUB>O<SUB>12</SUB>:Gd<SUP>3+</SUP> sample exhibits a sharp narrowband ultraviolet B emission at 311.9nm. The electron spin resonance spectrum of gadolinium doped Y<SUB>3</SUB>Ga<SUB>5</SUB>O<SUB>12</SUB> samples exhibit resonance signals with the effective g values at <I>g</I> ≈2.0, 2.2 and 5.8. These signals are attributed to Gd<SUP>3+</SUP> ion located in distorted surroundings experiencing a relatively strong crystal field.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A narrowband ultraviolet B emitting nano-garnet was synthesized. </LI> <LI> Narrow band centered at 311.9nm, good for phototherapy application. </LI> <LI> EPR results indicate the possible location of the Gd<SUP>3+</SUP> ion. </LI> <LI> Gd<SUP>3+</SUP> ion is likely to be located at the distorted dodecahedral site. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

COMMON FIXED POINTS OF COMPATIBLE MAPPINGS OF TYPE(A)

Pathak, H.K.,Kang, S.M. The Youngnam Mathematical Society Korea 1995 East Asian mathematical journal Vol.11 No.1

SOME FIXED POINT THEOREMS OF EXPANSION MAPPINGS

Pathak, H.K.,Kang, S.M.,Chang, S.S.,Ryu, J.W. The Youngnam Mathematical Society Korea 1995 East Asian mathematical journal Vol.11 No.1

Synthesis and investigations on correlation between EPR and optical properties of Fe doped Li₂SiO₃

Pathak, M.S.,Gopal, N.O.,Singh, N.,Mohapatra, M.,Rao, J.L.,Lee, Jung-Kul,Singh, Vijay Elsevier 2018 Journal of non-crystalline solids Vol.500 No.-

<P><B>Abstract</B></P> <P>Iron doped lithium metasilicate sample was synthesized using a combustion technique and characterized by XRD (X ray diffraction), SEM (scanning electron microscopy), FTIR (Fourier transform infrared spectroscopy), optical, and EPR (electron paramagnetic resonance) analyses. The phase purity of the combustion synthesized products was confirmed by XRD analysis. SEM data suggested the formation of a porous compound by virtue of the entrapment of the gases that evolved during the sample synthesis. FTIR data confirmed the formation of SiO bonds in the system. Optical data confirmed the existence of both divalent and trivalent iron in the system. Characteristic absorption bands in the region 215–270 nm and 535–620 nm were observed due to the presence of Fe<SUP>3+</SUP> in Oh and Td geometry respectively. On the other hand, the presence of bands at 967 and 1442 nm suggested the stabilisation of Fe<SUP>2+</SUP> also in both Oh and Td geometries, respectively. The divalent iron being a non-Kramer ion, could not be observed by EPR. However, strong temperature-dependent EPR signals were observed in the sample owing to Fe<SUP>3+</SUP>. By analyzing the EPR data, super-paramagnetic type of behaviour was observed in the system. Furthermore, the relaxation times along with other EPR spectroscopic parameters were estimated for the system.</P>

High sensitivity charge detection and dephasing in edge state interferometer

Pathak, P.K.,Lee, Y.,Kang, K. North-Holland 2010 Physica E, Low-dimensional systems & nanostructure Vol.42 No.4

We present an interferometry model of high sensitivity and high efficiency charge detectors in the integer quantum Hall regime. We show that the charge sensitivity in Fabry-Perot interferometer is higher than a Mach-Zehnder interferometer due to multiple reflections of electrons at quantum point contacts. We report the possibility of tuning Fabry-Perot interferometer for quantum limited detection for two quantum point contacts having different reflection probabilities. For systems with one quantum point contact and with two point contacts, we discuss improvement in sensitivity using electrons in spin entangled singlet pairs, injected through identically biased input terminals.

WEAK COMPATIBLE MAPPINGS OF TYPE (A) AND COMMON FIXED POINTS IN MENGER SPACES

Pathak, H.K.,Kang, S.M.,Baek, J.H. Korean Mathematical Society 1995 대한수학회논문집 Vol.10 No.1

The notion of probabilistic metric spaces (or statistical metric spaces) was introduced and studied by Menger [19] which is a generalization of metric space, and the study of these spaces was expanede rapidly with the pioneering works of Schweizer-Sklar [25]-[26]. The theory of probabilistic metric spaces is of fundamental importance in probabilistic function analysis. For the detailed discussions of these spaces and their applications, we refer to [9], [10], [28], [30]-[32], [36] and [39].

Narrowband ultraviolet B emitting Gd doped CaAl₂O₄ phosphors – An ESR and photoluminescence study

Pathak, M.S.,Singh, N.,Singh, Vijay,Watanabe, S.,Gundu Rao, T.K.,Seshadri, M.,Lee, Jung-Kul Elsevier 2018 Journal of luminescence Vol.204 No.-

<P><B>Abstract</B></P> <P>Phosphors with the composition Ca<SUB>1-x</SUB>Gd<SUB>x</SUB>Al<SUB>2</SUB>O<SUB>4</SUB> (x = 0.0025–0.09) were synthesized by a simple combustion route in a short time. The formation of the as-prepared combustion products was confirmed by the X-ray diffraction analysis, indicating the formation of a monoclinic phase. The PL spectroscopy assessment shows that with increasing Gd<SUP>3+</SUP> concentration, the ultraviolet emission from Gd<SUP>3+</SUP> at 314 nm (<SUP>6</SUP>P<SUB>7/2</SUB>→<SUP>8</SUP>S<SUB>7/2</SUB>) progressively enhanced. The Gd<SUP>3+</SUP>-doped CaAl<SUB>2</SUB>O<SUB>4</SUB> displays electron spin resonance signals with the effective g values at <I>g</I> ≈ 1.95, 2.9, and 3.7. Additional lines were also observed at the approximate g values of ~2.2 and 5.3. Gd<SUP>3+</SUP> ion located in the distorted surroundings and experiencing relatively strong crystal field, give rise to low field lines. Distorted surroundings in the present system may result from the nearness of the charge compensator oxygen vacancies.</P>

Polymeric microsphere-facilitated site-specific delivery of quercetin prevents senescence of pancreatic islets <i>in vivo</i> and improves transplantation outcomes in mouse model of diabetes

Pathak, Shiva,Regmi, Shobha,Nguyen, Tiep Tien,Gupta, Biki,Gautam, Milan,Yong, Chul Soon,Kim, Jong Oh,Son, Youlim,Kim, Jae-Ryong,Park, Min Hui,Bae, Young Kyung,Park, So Young,Jeong, Daewon,Yook, Simmyu Elsevier 2018 ACTA BIOMATERIALIA Vol.75 No.-

<P><B>Abstract</B></P> <P>Attenuation of senescence progression may be attractive way to preserve the functionality of pancreatic islets (PI) after transplantation. In this study, we developed a model for <I>in vitro</I> induction of premature senescence in rat PI and showed the effectiveness of quercetin (QU) to prevent the senescence. To provide targeted-delivery of QU to the PI after transplantation, we prepared the hybrid clusters (HC) of islet single cells (ISC) and QU-loaded polymeric microspheres (QU; ∼7.55 ng HC<SUP>−1</SUP>). Long-term culture of the HC revealed reduced levels of reactive oxygen species and decreased expression of senescence-associated beta galactosidase, Rb, p53, p16, and p21 compared to that of the control islets. Transplantation of HC into subcutaneous space of the immune-deficient mice produced better glycemic control compared to the control islets or the ICC-transplanted mice. SA-β-Gal staining of the <I>in vivo</I> transplanted HC sample showed lower intensity compared to that of the control islets or the islet cell clusters. Thus, <I>in situ</I> delivery of therapeutic agent may be a promising approach to improve therapeutic outcomes in cell therapy.</P> <P><B>Statement of Significance</B></P> <P>In this study, we aimed to improve outcomes in islet transplantation using <I>in situ</I> delivery of quercetin to pancreatic islets, using polymeric microspheres. We prepared prolonged release-type microspheres and constructed hybrid clusters of pancreatic islets and the microspheres using hanging drop method. The presence of quercetin in the cellular microenvironment attenuated the progression of senescence in the pancreatic islets in a long-term <I>in vitro</I> culture. Moreover, transplantation of the hybrid clusters in the diabetic mice produced better glycemic control compared to that of the control islets. In addition, quercetin delayed the progression of senescence in the pancreatic islets after <I>in vivo</I> transplantation. Thus, local delivery of antioxidants like quercetin may be an attractive way to improve outcomes in cell therapy.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Quercetin prevents senescence of pancreatic islets <I>in vitro</I>. </LI> <LI> PLGA microspheres provide quercetin into the cellular microenvironment. </LI> <LI> Transplantation of the hybrid clusters produces better glycemic control. </LI> <LI> Hybrid clusters of cells and microspheres exhibit reduction of senescence. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Influence of Dietary Supplementation of Condensed Tannins through Leaf Meal Mixture on Intake, Nutrient Utilization and Performance of Haemonchus contortus Infected Sheep

Pathak, A.K.,Dutta, Narayan,Banerjee, P.S.,Pattanaik, A.K.,Sharma, K. Asian Australasian Association of Animal Productio 2013 Animal Bioscience Vol.26 No.10

The study assessed the effect of dietary supplementation of leaf meal mixture (LMM) containing condensed tannins (CT) on feed intake, nutrient utilization and performance of sheep infected with Haemonchus contortus. Eighteen adult sheep of similar age and body weight ($25.03{\pm}1.52$) were included in this study and out of these, 12 sheep were infected with single dose of infective third stage larvae of H. contortus at 2,000 larvae per sheep. The experimental sheep were allocated in three different groups' i.e. negative control (NC; no infection), control (C; H. contortus infected) and treatment (T; H. contortus infected+CT at 1.5% of the DM through LMM) and the experiment was conducted for a period of 90 d. The intake of dry matter (DM), organic matter (OM) and digestibility of DM, OM, neutral detergent fibre (NDF) and acid detergent fibre (ADF) were comparable among three animal groups. However, digestibility of crude protein (CP) and ether extract (EE) were significantly (p<0.05) higher in NC group as compared to both C and T groups. Nitrogen (N) retention (g/d or % of N intake) was significantly (p = 0.038) lower in C group as compared to T and NC groups. Daily intake (g/kg $W^{0.75}$) of digestible crude protein (DCP), digestible organic matter (DOM) and total digestible nutrient (TDN) did not differ significantly (p<0.05) in the three groups. Haemoglobin (Hb) and packed cell volume (PCV) were significantly (p<0.001) higher in treatment group as compared to control. The level of Hb and PCV reduced (p<0.001) after 30 days of experimental feeding. CT significantly (p<0.001) reduced serum urea in T group as compared to NC and C groups. Serum proteins differed significantly (p<0.01) among the three groups. The activity of serum enzymes AST, ALT, ALP and LDH were also statistically non significant (p<0.05) among treatments. The weight of abomasal lymph nodes (ALN) in T group was higher (p<0.05) than in C group. Treatment group had lower (p<0.05) total worms and fecal egg count compared to control group. It may be concluded that dietary supplementation of CT through LMM significantly improved the N retention, and inhibited the different developmental stages of Haemonchus contortus in experimental sheep.