EXPRESS: Effectiveness of HMG-CoA reductase inhibitors on inflammation and metabolic markers in the US-Mexico border Hispanic population.

HMG-CoA reductase inhibitors (statins) are commonly used for dyslipidemia management to reduce the risk of cardiovascular disease (CVD). High-sensitivity C-reactive protein (hs-CRP) is an emerging systematic low-grade inflammatory marker associated with atherosclerotic CVD development. Despite racial/ethnic disparities in the use and response of statins and the anti-inflammatory effects of statins, the effectiveness of statins on inflammation and metabolic markers is unknown among Hispanics. We performed a retrospective cohort study using 150 adult patients scheduled for an annual physical exam at a family medicine clinic between January 1, 2021, and December 31, 2021. Effect size with a 95% confidence interval (CI) was estimated using adjusted regression analyses. Among 150 patients, 52 (34.67%) received statins. Patients who received statins had significantly reduced median hs-CRP (1.9 vs. 3.2, p=0.007), mean low-density lipoprotein (LDL-C) (101.18 vs. 124.6, p<0.001), and total cholesterol (172.6 vs. 194.5, p<0.001) concentrations compared to those who did not receive statins. In the propensity-scores matched analysis, lower concentrations of log-transformed hs-CRP (regression coefficient [RC], -0.48; 95%CI: -0.89, -0.07), LDL-C (RC, -19.57; 95%CI: -33.04, -6.1), and total cholesterol (RC, -23.47; 95%CI: -38.96, -7.98) were associated with statin use. In addition, hepatic steatosis (adjusted relative risk [aRR]=0.25; 95%CI: 0.08, 0.78, p= 0.017) was significantly lower among patients with the use of statins. Our study suggests that HMG-CoA reductase inhibitors may help reduce inflammation among Hispanic patients with dyslipidemia and hypertension. These findings have useful implications for preventing risk and disparities associated with cardiovascular and other inflammatory-induced diseases among the fastest-growing US Hispanic minorities.

Role of Histone Deacetylase Inhibitor in Diabetic Painful Neuropathy.

Diabetic painful neuropathy (DPN) is one of the most detrimental complications of diabetes. Alterations in neuroinflammatory mediators play significant roles in the development of DPN. Infiltration of the neutrophils and monocyte/macrophages contributes substantial role in the degenerative process of the distal sciatic nerve by forming neutrophil extracellular traps (NETs) under diabetic condition. Citrullination of histones due to increase in protein arginine deiminase (PAD) enzyme activity under hyperglycemia may promote NET formation, which can further increase the cytokine production by activating macrophages and proliferation of neutrophils. This study reveals that the increase in histone deacetylases (HDAC) is crucial in DPN and inhibition of HDAC using HDAC inhibitor (HDACi) FK228 would suppress NETosis and alleviate diabetic nerve degeneration and pain. FK228, also known as romidepsin, is FDA approved for the treatment of cutaneous T-cell lymphoma yet the molecular mechanisms of this drug are not completely understood in DPN. In this study, type 2 diabetic (T2D) mice with pain were treated with HDACi, FK228 1 mg/kg; I.P. 2 × /week for 3 weeks. The results demonstrate that FK228 treatment can alleviate thermal hyperalgesia and mechanical allodynia significantly along with changes in the expression of HDACs in the dorsal root ganglia (DRG) and spinal cord dorsal horn neurons of diabetic animals. The results also indicate that FK228 treatment can alter the expression of neutrophil elastase (NE), extracellular or cell free DNA (cfDNA), citrullinated histone-3 (CitH3), PADI4, growth-associated protein (GAP)-43, and glucose transporter (GLUT)-4. Overall, this study suggests that FK228 could amend the expression of nerve regeneration markers and inflammatory mediators in diabetic animals and may offer an alternative treatment approach for DPN.

Psychological Stress Experienced by First-Year Medical Undergraduates: A Cross-Sectional Study From Eastern India.

Background While medical education is vital for producing competent physicians, its rigorous curriculum can harm students' mental well-being. This study focuses on assessing psychological stress in first-year medical students in Eastern India and aims to identify its primary causes. Methods This cross-sectional study involved 125 first-year MBBS students in a tertiary care medical teaching institution in eastern India. They completed the Medical Student Stressor Questionnaire (MSSQ-40) questionnaire to measure stress and provided academic records to be reviewed.  Results Among the 125 students included in the study, male students demonstrated greater academic and interpersonal stress. The findings revealed that a substantial proportion (79%) of the student population experienced high to severe levels of academic stress, followed by 88% who reported moderate to high levels of social-related stress. Furthermore, it was observed that those students who experienced high to severe stress across all six domains tended to perform poorly during the initial half of their academic year. Conclusion The high levels of stress experienced by medical students can have significant implications for their academic performance. However, the nature of our study limits us to only highlight the existence of a correlation between the two. Future studies on the same should be conducted to assess the causal relation between these factors.

Inhibiting Fatty Acid Amide Hydrolase Ameliorates Enteropathy in Diabetic Mice: A Cannabinoid 1 Receptor Mediated Mechanism.

Gastrointestinal (GI) dysmotility in diabetics exhibits fecal incontinence or constipation which affects patients' quality of life. In this study, we aimed to understand the pattern of GI transit in type 1 diabetic (T1D) mice and whether inhibiting endocannabinoid degradation would exhibit therapeutic effect. Whole gut-transit time and fecal-pellet output were measured at 16 week post-diabetes. T1D mice treated with fatty acid amide hydrolase (FAAH) inhibitor URB597 showed reduced fecal output as well as improved gut transit time. Cannabinoid 1 receptor antagonist, AM251 blocked the effects of URB597, which may demonstrate that FAAH inhibitor is a potential remedial strategy for GI dysmotility.

3D Biofabrication of a Cardiac Tissue Construct for Sustained Longevity and Function.

In this study, we developed three-dimensional (3D) printed annular ring-like scaffolds of hydrogel (gelatin-alginate) constructs encapsulated with a mixture of human cardiac AC16 cardiomyocytes (CMs), fibroblasts (CFs), and microvascular endothelial cells (ECs) as cardiac organoid models in preparation for investigating the role of microgravity in cardiovascular disease initiation and development. We studied the mechanical properties of the acellular scaffolds and confirmed their cell compatibility as well as heterocellular coupling for cardiac tissue engineering. Rheological analysis performed on the acellular scaffolds showed the scaffolds to be elastogenic with elastic modulus within the range of a native in vivo heart tissue. The microstructural and physicochemical properties of the scaffolds analyzed through scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy-attenuated total reflectance (ATR-FTIR) confirmed the mechanical and functional stability of the scaffolds for long-term use in in vitro cell culture studies. HL-1 cardiomyocytes bioprinted in these hydrogel scaffolds exhibited contractile functions over a sustained period of culture. Cell mixtures containing CMs, CFs, and ECs encapsulated within the 3D printed hydrogel scaffolds exhibited a significant increase in viability and proliferation over 21 days, as shown by flow cytometry analysis. Moreover, via the expression of specific cardiac biomarkers, cardiac-specific cell functionality was confirmed. Our study depicted the heterocellular cardiac cell interactions, which is extremely important for the maintenance of normal physiology of the cardiac wall in vivo and significantly increased over a period of 21 days in in vitro. This 3D bioprinted "cardiac organoid" model can be adopted to simulate cardiac environments in which cellular crosstalk in diseased pathologies like cardiac atrophy can be studied in vitro and can further be used for drug cytotoxicity screening or underlying disease mechanisms.

Perception of Online Learning Among Undergraduate Medical Students of Eastern India: A Cross-Sectional Study.

Background In 2020 WHO declared the coronavirus disease 2019 (COVID-19) outbreak as a global pandemic. To flatten the curve of infection, a nationwide lockdown was declared by the Indian government. All the schools and colleges were shut for an indefinite period. Like all other streams, medical education also got severely hampered. Adapting themselves to the changing environment, teachers started using different teaching-learning methods and media to get across to the students. The objective of the research was to study the perception of medical students towards online teaching during the COVID pandemic. Methods A descriptive cross-sectional study was conducted by the distribution of a pre-validated online questionnaire to medical students of West Bengal. From the collected data, relevant statistical averages and census domains were calculated. The chi-square test was done and assessed with a p≤0.05 significance level. Results A significant increase was noted in the time spent by students on various online teaching activities (p<0.05). Video tutorials, e.g., YouTube, were ranked as the most effective mode (17.2%), followed by live tutorials via Microsoft Teams, etc. (8.9%). A significant number (30.2%) of students strongly favoured online teaching over face-to-face teaching. Major challenges of online learning cited by students were internet connectivity issues (79.8%) followed by family distraction (37.9 %) and inconvenient timing of the classes (20.1%). Conclusion Our study highlighted the benefits, disadvantages and barriers to online learning from the perspective of undergraduate medical education in India. Even though the online mode of teaching was found to be beneficial in the context of the COVID-19 pandemic, it cannot be used as an absolute substitution for face-to-face teaching in the given context.

Changes in Stress-Mediated Markers in a Human Cardiomyocyte Cell Line under Hyperglycemia.

Diabetes is a major risk factor for cardiovascular diseases, especially cardiomyopathy, a condition in which the smooth muscles of the heart become thick and rigid, affecting the functioning of cardiomyocytes, the contractile cells of the heart. Uncontrolled elevated glucose levels over time can result in oxidative stress, which could lead to inflammation and altered epigenetic mechanisms. In the current study, we investigated whether hyperglycemia can modify cardiac function by directly affecting these changes in cardiomyocytes. To evaluate the adverse effect of high glucose, we measured the levels of gap junction protein, connexin 43, which is responsible for modulating cardiac electric activities and Troponin I, a part of the troponin complex in the heart muscles, commonly used as cardiac markers of ischemic heart disease. AC16 human cardiomyocyte cells were used in this study. Under hyperglycemic conditions, these cells demonstrated altered levels of connexin 43 and Troponin-I after 24 h of exposure. We also examined hyperglycemia induced changes in epigenetic markers: H3K9me1, Sirtuin-1 (SIRT1), and histone deacetylase (HDAC)-2 as well as in inflammatory and stress-related mediators, such as heat shock protein (HSP)-60, receptor for advanced glycation end products (RAGE), toll-like receptor (TLR)-4, high mobility group box (HMGB)-1 and CXC chemokine receptor (CXCR)-4. Cardiomyocytes exposed to 25mM glucose resulted in the downregulation of HSP60 and SIRT1 after 48 h. We further examined that hyperglycemia mediated the decrease in the gap junction protein CX43, as well as CXC chemokine receptor CXCR4 which may affect the physiological functions of the cardiomyocytes when exposed to high glucose for 24 and 48 h. Upregulated expression of DNA-binding nuclear protein HMGB1, along with changes in histone methylation marker H3K9me1 have demonstrated hyperglycemia-induced damage to cardiomyocyte at 24 h of exposure. Our study established that 24 to 48 h of hyperglycemic exposure could stimulate stress-mediated inflammatory mediators in cardiomyocytes in vitro. These stress-related changes in hyperglycemia-induced cardiomyocytes may further initiate an increase in injury markers which eventually could alter the epigenetic processes. Therefore, epigenetic and inflammatory mechanisms in conjunction with alterations in a downstream signaling pathway could have a direct effect on the functionality of the cardiomyocytes exposed to high glucose during short and long-term exposures.

Effect of Nutritional Supplementation on Oxidative Stress and Hormonal and Lipid Profiles in PCOS-Affected Females.

Polycystic ovary syndrome (PCOS) affects several reproductive and endocrine features in females and has a poorly understood etiology. Treatment strategies for PCOS are limited and are based primarily on diet and nutrient supplementation. Recent studies have recommended some nutrients such as vitamins, minerals and vitamin-like nutrients for the therapy for PCOS. Therefore, it is claimed that the cause of PCOS could be vitamin or mineral deficiency. This review provides a narrative on the effect of nutritional supplementation on oxidative stress induced in PCOS. Oxidative stress plays a formative role in PCOS pathophysiology. This article reviews oxidative stress, its markers, nutritional supplementation and clinical studies. We also aim to show the effect of nutritional supplementation on genes affecting hormonal and glucose-mediated pathways.

Cardioprotective Effect of Glycyrrhizin on Myocardial Remodeling in Diabetic Rats.

Myocardial fibrosis is one of the major complications of long-term diabetes. Hyperglycemia induced cardiomyocyte atrophy is a frequent pathophysiological indicator of diabetic heart. The objective of this study was to investigate the cardioprotective effect of glycyrrhizin (GLC) on myocardial damage in diabetic rats and assess the anti-inflammatory and anti-fibrotic effect of GLC. Our study demonstrates that hyperglycemia can elevate cardiac atrophy in diabetic animals. Type 2 diabetic fatty and the lean control rats were evaluated for cardiac damage and inflammation at 8-12 weeks after the development of diabetes. Western blot and immunohistochemical studies revealed that gap junction protein connexin-43 (CX43), cardiac injury marker troponin I, cardiac muscle specific voltage gated sodium channel NaV1.5 were significantly altered in the diabetic heart. Furthermore, oxidative stress mediator receptor for advanced glycation end-products (RAGE), as well as inflammatory mediator phospho-p38 MAPK and chemokine receptor CXCR4 were increased in the diabetic heart whereas the expression of nuclear factor erythroid-2-related factor 2 (Nrf2), the antioxidant proteins that protect against oxidative damage was reduced. We also observed an increase in the expression of the pleiotropic cytokine, transforming growth factor beta (TGF-ß) in the diabetic heart. GLC treatment exhibited a decrease in the expression of phospho-p38 MAPK, RAGE, NaV1.5 and TGF-ß and it also altered the expression of CX43, CXCR4, Nrf2 and troponin I. These observations suggest that GLC possesses cardioprotective effects in diabetic cardiac atrophy and that these effects could be mediated through activation of Nrf2 and inhibition of CXCR4/SDF1 as well as TGF-ß/p38MAPK signaling pathway.

3D Bioprinted Spheroidal Droplets for Engineering the Heterocellular Coupling between Cardiomyocytes and Cardiac Fibroblasts.

Since conventional human cardiac two-dimensional (2D) cell culture and multilayered three-dimensional (3D) models fail in recapitulating cellular complexity and possess inferior translational capacity, we designed and developed a high-throughput scalable 3D bioprinted cardiac spheroidal droplet-organoid model with cardiomyocytes and cardiac fibroblasts that can be used for drug screening or regenerative engineering applications. This study helped establish the parameters for bioprinting and cross-linking a gelatin-alginate-based bioink into 3D spheroidal droplets. A flattened disk-like structure developed in prior studies from our laboratory was used as a control. The microstructural and mechanical stability of the 3D spheroidal droplets was assessed and was found to be ideal for a cardiac scaffold. Adult human cardiac fibroblasts and AC16 cardiomyocytes were mixed in the bioink and bioprinted. Live-dead assay and flow cytometry analysis revealed robust biocompatibility of the 3D spheroidal droplets that supported the growth and proliferation of the cardiac cells in the long-term cultures. Moreover, the heterocellular gap junctional coupling between the cardiomyocytes and cardiac fibroblasts further validated the 3D cardiac spheroidal droplet model.

Methods for histological characterization of cryo-induced myocardial infarction in a rat model.

Ligation of the left anterior descending (LAD) coronary artery has been commonly employed to induce myocardial infarction (MI) in animals; however, it is known to pose setbacks in the form of cardiac arrhythmias and unpredictable areas of necrotic damage. Cryo-infarction is an alternate method that has been adopted to create a reproducible model of a myocardial injury. In this study, Sprague-Dawley rats were subjected to thoracotomy followed by cryo-induced infarction of the heart, while the control-sham group was only subjected to thoracotomy following which the heart was collected from all animals. Tissue sections were stained with hematoxylin and eosin and analyzed to determine cardiac muscle density, fiber length, and fiber curvature. Observations revealed reduced muscle density, cardiac fiber length, and distorted fibers in infarcted tissue sections. Gomori's Trichrome staining was performed on tissue sections to study the effects of post MI on collagen, which showed enhanced intensity of collagen staining indicating fibrosis for the experimental models as compared to the sham models, an established consequence to myocardial injury. Immunohistochemical staining of the tissue sections with DAPI and connexin-43 (Cx-43) revealed that there was reduced DAPI staining and a less pronounced expression of Cx-43 in the experimental samples as compared to the sham samples. Results implied significant cell damage resulting from the cryo-infarction, subsequently disrupting and disaggregating the functional Cx-43 junction in cardiac myocytes, which is essential for normal and healthy cardiac physiology and function. This quantitative histological study of cryo-induced MI in a rat model can aid others attempting to optimize MI models in rats via cryo-injury, to study cardiac disease progression, and to aid in the construction of engineered cardiac tissues.

Role of Minerals and Trace Elements in Diabetes and Insulin Resistance.

Minerals and trace elements are micronutrients that are essential to the human body but present only in traceable amounts. Nonetheless, they exhibit well-defined biochemical functions. Deficiencies in these micronutrients are related to widespread human health problems. This review article is focused on some of these minerals and trace element deficiencies and their consequences in diabetes and insulin resistance. The levels of trace elements vary considerably among different populations, contingent on the composition of the diet. In several Asian countries, large proportions of the population are affected by a number of micronutrient deficiencies. Local differences in selenium, zinc, copper, iron, chromium and iodine in the diet occur in both developed and developing countries, largely due to malnutrition and dependence on indigenous nutrition. These overall deficiencies and, in a few cases, excess of essential trace elements may lead to imbalances in glucose homeostasis and insulin resistance. The most extensive problems affecting one billion people or more worldwide are associated with inadequate supply of a number of minerals and trace elements including iodine, selenium, zinc, calcium, chromium, cobalt, iron, boron and magnesium. This review comprises various randomized controlled trials, cohort and case-controlled studies, and observational and laboratory-based studies with substantial outcomes of micronutrient deficiencies on diabetes and insulin resistance in diverse racial inhabitants from parts of Asia, Africa, and North America. Changes in these micronutrient levels in the serum and urine of subjects may indicate the trajectory toward metabolic changes, oxidative stress and provide disease-relevant information.

High-Mobility Group Box 1 Protein Signaling in Painful Diabetic Neuropathy.

Diabetes is a global epidemic and more than 50% diabetic patients are also diagnosed with neuropathy, which greatly affects the quality of life of the patients. Available treatments are not always successful due to the limited efficacy and complications, such as addiction and dependency. Studies have implicated that high mobility group box1 (HMGB1) protein plays a crucial role in neuroinflammation and the development of neuropathic conditions. HMGB1 is a proinflammatory cytokine that can be released from necrotic cells in passive form or in response to inflammatory signals as an active form. HMGB1 is the ligand for the receptor for advanced glycation end products (RAGE), and toll-like receptors, (TLR)-2 and TLR4, which also indirectly activates C-X-C chemokine receptor type 4 (CXCR4). We investigated whether blocking of HMGB1 can reduce pain and inflammation in diabetic neuropathic animals to further understand the role of HMGB1 in diabetic neuropathy. Type 2 diabetic rats and mice were treated with natural inhibitor of HMGB1, glycyrrhizin (GLC) for five days/week for four weeks at a dose of 50 mg/kg per day by intraperitoneal injection. The animals were divided into three categories: naïve control, diabetic alone, diabetic with GLC treatment. All of the behavioral analyses were conducted before and after the treatment. The expression of inflammatory markers and changes in histone acetylation in the peripheral nervous system were measured by immunohistochemistry and Western blot analysis after the completion of the treatment. Our study revealed that TLR4, HMGB1, CXCR4, and Nod-like receptor protein 3 (NLRP3) levels were increased in the spinal and dorsal root ganglia (DRG) neurons of Type 2 diabetic mice and rats with painful neuropathy. GLC treatment inhibited the increases in TLR4, NLRP3, and CXCR4 expressions and improved the mechanical and thermal pain threshold in these animals. Immunohistochemical studies revealed that hyperglycemia mediated inflammation influenced HMGB1 acetylation and its release from the neurons. It also altered histone 3 acetylation in the microglial cells. The inhibition of HMGB1 by GLC prevented the release of HMGB1 as well as H3K9 acetylation. These findings indicate that the interruption of HMGB1 mediated inflammation could ameliorate diabetic neuropathy and might exhibit a unique target for the treatment.

The applicability of furfuryl-gelatin as a novel bioink for tissue engineering applications.

Three-dimensional bioprinting is an innovative technique in tissue engineering, to create layer-by-layer structures, required for mimicking body tissues. However, synthetic bioinks do not generally possess high printability and biocompatibility at the same time. So, there is an urgent need for naturally derived bioinks that can exhibit such optimized properties. We used furfuryl-gelatin as a novel, visible-light crosslinkable bioink for fabricating cell-laden structures with high viability. Hyaluronic acid was added as a viscosity enhancer and either Rose Bengal or Riboflavin was used as a visible-light crosslinker. Crosslinking was done by exposing the printed structure for 2.5 min to visible light and confirmed using Fourier transform infrared spectroscopy and rheometry. Scanning electron microscopy revealed a highly porous networked structure. Three different cell types were successfully bioprinted within these constructs. Mouse mesenchymal stem cells printed within monolayer and bilayer sheets showed viability, network formation and proliferation (∼5.33 times) within 72 h of culture. C2C12 and STO cells were used to print a double layered structure, which showed evidence of the viability of both cells and heterocellular clusters within the construct. This furfuryl-gelatin based bioink can be used for tissue engineering of complex tissues and help in understanding how cellular crosstalk happens in vivo during normal or diseased pathology. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 314-323, 2019.

A Visible Light-Cross-Linkable, Fibrin-Gelatin-Based Bioprinted Construct with Human Cardiomyocytes and Fibroblasts.

In this study, fibrin was added to a photo-polymerizable gelatin-based bioink mixture to fabricate cardiac cell-laden constructs seeded with human induced pluripotent stem cell-derived cardiomyocytes (iPS-CM) or CM cell lines with cardiac fibroblasts (CF). The extensive use of platelet-rich fibrin, its capacity to offer patient specificity, and the similarity in composition to surgical glue prompted us to include fibrin in the existing bioink composition. The cell-laden bioprinted constructs were cross-linked to retain a herringbone pattern via a two-step procedure including the visible light cross-linking of furfuryl-gelatin followed by the chemical cross-linking of fibrinogen via thrombin and calcium chloride. The printed constructs revealed an extremely porous, networked structure that afforded long-term in vitro stability. Cardiomyocytes printed within the sheet structure showed excellent viability, proliferation, and expression of the troponin I cardiac marker. We extended the utility of this fibrin-gelatin bioink toward coculturing and coupling of CM and cardiac fibroblasts (CF), the interaction of which is extremely important for maintenance of normal physiology of the cardiac wall in vivo. This enhanced "cardiac construct" can be used for drug cytotoxicity screening or unraveling triggers for heart diseases in vitro.

The Efficacy of Graphene Foams for Culturing Mesenchymal Stem Cells and Their Differentiation into Dopaminergic Neurons.

The implantation of stem cells in vivo is the ideal approach for the restoration of normal life functions, such as replenishing the decreasing levels of affected dopaminergic (DA) neurons during neurodegenerative disease conditions. However, combining stem cells with biomaterial scaffolds provides a promising strategy for engineering tissues or cellular delivery for directed stem cell differentiation as a means of replacing diseased/damaged tissues. In this study, mouse mesenchymal stem cells (MSCs) were differentiated into DA neurons using sonic hedgehog, fibroblast growth factor, basic fibroblast growth factor, and brain-derived neurotrophic factor, while they were cultured within collagen-coated 3D graphene foams (GF). The differentiation into DA neurons within the collagen-coated GF and controls (collagen gels, plastic) was confirmed using ß-III tubulin, tyrosine hydroxylase (TH), and NeuN positive immunostaining. Enhanced expression of ß-III tubulin, TH, and NeuN and an increase in the average neurite extension length were observed when cells were differentiated within collagen-coated GF in comparison with collagen gels. Furthermore, these graphene-based scaffolds were not cytotoxic as MSC seemed to retain viability and proliferated substantially during in vitro culture. In summary, these results suggest the utility of 3D graphene foams towards the differentiation of DA neurons from MSC, which is an important step for neural tissue engineering applications.

Early Urinary Markers for Diabetic and Other Kidney Diseases.

BACKGROUND: Nephropathy is a debilitating complication of diabetes associated with increased risk for renal failure, leading to poor quality of life of the affected patients and eventually to mortality. Early intervention is crucial to enhance the well-being of the patients with nephropathy. Albuminuria is a well-known predictor of weak renal outcomes in patients with diabetes and hypertension, unfortunately, it is not an early marker for kidney injury. OBJECTIVE: Assessment of new and precise markers is necessary to predict the early onset and progression of nephropathy. It is important to find early markers which could predict kidney injury even before the clinical signs (no microalbuminuria) appear. RESULTS: Prevention and therapy for kidney diseases using surrogate markers such as serum creatinine have not proven to be better indicators for interventions that have been shown to decrease morbidity or mortality. A number of studies have elucidated the importance of kidney injury markers. This article describes the significance of urinary markers such as nephrin, Cystatin C, Monocyte chemoattractant protein (MCP-1), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM- 1) and nestin, which are associated with early renal dysfunction. CONCLUSION: Although significant advances have been made in medical therapy, the degree of morbidity and mortality associated with kidney diseases remain despondently high. Besides the serum markers, urinary markers may provide a better prediction of progression of the damage to the kidneys in diabetic patients.

Delivery of Mesenchymal Stem Cells from Gelatin-Alginate Hydrogels to Stomach Lumen for Treatment of Gastroparesis.

Gastroparesis (GP) is associated with depletion of interstitial cells of Cajal (ICCs) and enteric neurons, which leads to pyloric dysfunction followed by severe nausea, vomiting and delayed gastric emptying. Regenerating these fundamental structures with mesenchymal stem cell (MSC) therapy would be helpful to restore gastric function in GP. MSCs have been successfully used in animal models of other gastrointestinal (GI) diseases, including colitis. However, no study has been performed with these cells on GP animals. In this study, we explored whether mouse MSCs can be delivered from a hydrogel scaffold to the luminal surfaces of mice stomach explants. Mouse MSCs were seeded atop alginate-gelatin, coated with poly-l-lysine. These cell-gel constructs were placed atop stomach explants facing the luminal side. MSCs grew uniformly all across the gel surface within 48 h. When placed atop the lumen of the stomach, MSCs migrated from the gels to the tissues, as confirmed by positive staining with vimentin and N-cadherin. Thus, the feasibility of transplanting a cell-gel construct to deliver stem cells in the stomach wall was successfully shown in a mice stomach explant model, thereby making a significant advance towards envisioning the transplantation of an entire tissue-engineered 'gastric patch' or 'microgels' with cells and growth factors.

Role of Glycyrrhizin in the Reduction of Inflammation in Diabetic Kidney Disease.

BACKGROUND: Diabetic kidney disease (DKD) is one of the most debilitating complications of type 2 diabetes. Recent evidence suggests chronic inflammation to be one of the causal factors of DKD. The mechanisms entailed are not completely elucidated except that a variety of cytokines play a major role in this process. High mobility group box 1 (HMGB1) is a pro-inflammatory toll-like receptor-4 (TLR4)-binding cytokine that is involved in inflammation-associated gene expression. This investigation was designed to assess the involvement of HMGB1, TLR-4, and nuclear factor (NF)-κB in the development of DKD and to evaluate that whether blocking HMGB1 by its natural inhibitor Glycyrrhizin (GLC) can reduce the progression of the disease. METHODS: Studies were carried out in 8-10-weeks old Zucker diabetic fatty (ZDF) and lean, age- and gender-matched rats. At 10 weeks of age, ZDF rats as compared to controls, showed hyperglycemia, without proteinuria. After 8-10 weeks of the development of diabetes, ZDF animals that showed proteinuria were treated with GLC for 4 weeks. In addition, normal rat kidney (NRK-52E) cells with epithelial-like morphology were comparatively treated with GLC under hyperglycemic condition in vitro. RESULTS: Substantial increase in the expression of HMGB1, TLR4, and NF-κB in vivo and in vitro under hyperglycemic conditions was observed as compared to normoglycemic conditions. The overexpression of HMGB1, TLR4, NF-κB, and glomerular injury marker nestin was significantly ameliorated by GLC administration. CONCLUSION: Our findings suggest that hyperglycemia-induced HMGB1 activation in ZDF rats may contribute to the progression of DKD.