Food environment and diabetes mellitus in South Asia: A geospatial analysis of health outcome data

BackgroundThe global epidemic of type 2 diabetes mellitus (T2DM) renders its prevention a major public health priority. A key risk factor of diabetes is obesity and poor diets. Food environments have been found to influence people’s diets and obesity, positing they may play a role in the prevalence of diabetes. Yet, there is scant evidence on the role they may play in the context of low- and middle-income countries (LMICs). We examined the associations of food environments on T2DM among adults and its heterogeneity by income and sex.Methods and findingsWe linked individual health outcome data of 12,167 individuals from a network of health surveillance sites (the South Asia Biobank) to the density and proximity of food outlets geolocated around their homes from environment mapping survey data collected between 2018 and 2020 in Bangladesh and Sri Lanka. Density was defined as share of food outlets within 300 m from study participant’s home, and proximity was defined as having at least 1 outlet within 100 m from home. The outcome variables include fasting blood glucose level, high blood glucose, and self-reported diagnosed diabetes. Control variables included demographics, socioeconomic status (SES), health status, healthcare utilization, and physical activities. Data were analyzed in ArcMap 10.3 and STATA 15.1. A higher share of fast-food restaurants (FFR) was associated with a 9.21 mg/dl blood glucose increase (95% CI: 0.17, 18.24; p < 0.05). Having at least 1 FFR in the proximity was associated with 2.14 mg/dl blood glucose increase (CI: 0.55, 3.72; p < 0.01). A 1% increase in the share of FFR near an individual’s home was associated with 8% increase in the probability of being clinically diagnosed as a diabetic (average marginal effects (AMEs): 0.08; CI: 0.02, 0.14; p < 0.05). Having at least 1 FFR near home was associated with 16% (odds ratio [OR]: 1.16; CI: 1.01, 1.33; p < 0.05) and 19% (OR: 1.19; CI: 1.03, 1.38; p < 0.05) increases in the odds of higher blood glucose levels and diagnosed diabetes, respectively. The positive association between FFR density and blood glucose level was stronger among women than men, but the association between FFR proximity and blood glucose level was stronger among men as well as among those with higher incomes. One of the study’s key limitations is that we measured exposure to food environments around residency geolocation; however, participants may source their meals elsewhere.ConclusionsOur results suggest that the exposure to fast-food outlets may have a detrimental impact on the risk of T2DM, especially among females and higher-income earners. Policies should target changes in the food environments to promote better diets and prevent T2DM.

Dian Kusuma and colleagues investigate the associations between exposure to the density and proximity of healthy and unhealthy food outlets and diabetes in Bangladesh and Sri Lanka.     

An epigenetic small molecule screen to target abnormal nuclear morphology in human cells

Irregular nuclear shapes are a hallmark of human cancers. Recent studies suggest that alterations to chromatin regulators may cause irregular nuclear morphologies. Here we screened an epigenetic small molecule library consisting of 145 compounds against chromatin regulators for their ability to revert abnormal nuclear shapes that were induced by gene knockdown in noncancerous MCF10A human mammary breast epithelial cells. We leveraged a previously validated quantitative Fourier approach to quantify the elliptical Fourier coefficient (EFC ratio) as a measure of nuclear irregularities, which allowed us to perform rigorous statistical analyses of screening data. Top hit compounds fell into three major mode of action categories, targeting three separate epigenetic modulation routes: 1) histone deacetylase inhibitors, 2) bromodomain and extraterminal domain protein inhibitors, and 3) methyl-transferase inhibitors. Some of the top hit compounds were also efficacious in reverting nuclear irregularities in MDA-MB-231 triple negative breast cancer cells and in PANC-1 pancreatic cancer cells in a cell-type-dependent manner. Regularization of nuclear shapes was compound-specific, cell-type specific, and dependent on the specific molecular perturbation that induced nuclear irregularities. Our approach of targeting nuclear abnormalities may be potentially useful in screening new types of cancer therapies targeted toward chromatin structure.     

Novel hits for acetylcholinesterase inhibition derived by docking-based screening on ZINC database

The inhibition of the enzyme acetylcholinesterase (AChE) increases the levels of the neurotransmitter acetylcholine and symptomatically improves the affected cognitive function. In the present study, we searched for novel AChE inhibitors by docking-based virtual screening of the standard lead-like set of ZINC database containing more than 6 million small molecules using GOLD software. The top 10 best-scored hits were tested in vitro for AChE affinity, neurotoxicity, GIT and BBB permeability. The main pharmacokinetic parameters like volume of distribution, free fraction in plasma, total clearance, and half-life were predicted by previously derived models. Nine of the compounds bind to the enzyme with affinities from 0.517 to 0.735?µM, eight of them are non-toxic. All hits permeate GIT and BBB and bind extensively to plasma proteins. Most of them are low-clearance compounds. In total, seven of the 10 hits are promising for further lead optimisation. These are structures with ZINC IDs: 00220177, 44455618, 66142300, 71804814, 72065926, 96007907, and 97159977.     

New host plants of Erwinia amylovora in Bulgaria

Nine strains of Erwinia amylovora were isolated from new host plants in Bulgaria--chokeberry and strawberry. The strains were characterized morphologically and biochemically using the API 20E and BIOLOG system. It was established that they showed three different API 20E metabolic profiles, not found by previous studies of E. amylovora. All strains were identified as E. amylovora due to their metabolic fingerprint patterns obtained by the BIOLOG system. The identification was confirmed by PCR amplification of a specific region of plasmid pEA29 and genome ams-region. This study is the first characterization and identification of E. amylovora strains isolated from chokeberry and strawberry by the API 20E and BIOLOG system and by polymerase chain reaction.     

A novel kinase function of a nucleoside‐diphosphate‐kinase homologue in Porphyromonas gingivalis is critical in subversion of host cell apoptosis by targeting heat‐shock protein 27

We have previously shown that a homologue of a conserved nucleoside‐diphosphate‐kinase (Ndk) family of multifunctional enzymes and secreted molecule in Porphyromonas gingivalis can modulate select host molecular pathways including downregulation of reactive‐oxygen‐species generation to promote bacterial survival in human gingival epithelial cells (GECs). In this study, we describe a novel kinase function for bacterial effector, P. gingivalis‐Ndk, in abrogating epithelial cell death by phosphorylating heat‐shock protein 27 (HSP27) in GECs. Infection by P. gingivalis was recently suggested to increase phosphorylation of HSP27 in cancer‐epithelial cells; however, the mechanism and biological significance of antiapoptotic phospho‐HSP27 during infection has never been characterised. Interestingly, using glutathione S‐transferase‐rNdk pull‐down analysed by mass spectrometry, we identified HSP27 in GECs as a strong binder of P. gingivalis‐Ndk and further verified using confocal microscopy and ELISA. Therefore, we hypothesised P. gingivalis‐Ndk can phosphorylate HSP27 for inhibition of apoptosis in GECs. We further employed P. gingivalis‐Ndk protein constructs and an isogenic P. gingivalis‐ndk‐deficient‐mutant strain for functional examination. P. gingivalis‐infected GECs displayed significantly increased phospho‐HSP27 compared with ndk‐deficient‐strain during 24 hr infection. Phospho‐HSP27 was significantly increased by transfection of GFP‐tagged‐Ndk into uninfected‐GECs, and in vitro phosphorylation assays revealed direct phosphorylation of HSP27 at serines 78 and 82 by P. gingivalis‐Ndk. Depletion of HSP27 via siRNA significantly reversed resistance against staurosporine‐mediated‐apoptosis during infection. Transfection of recombinant P. gingivalis‐Ndk protein into GECs substantially decreased staurosporine‐induced‐apoptosis. Finally, ndk‐deficient‐mutant strain was unable to inhibit staurosporine‐induced Cytochrome C release/Caspase‐9 activation. Thus, we show for the first time the phosphorylation of HSP27 by a bacterial effector—P. gingivalis‐Ndk—and a novel function of Ndks that is directly involved in inhibition of host cell apoptosis and the subsequent bacterial survival.     

Expression,localization and possible functions of aquaporins 3 and 8 in rat digestive system

Although aquaporins (AQPs) play important roles in transcellular water movement, their precise quantification and localization remains controversial. We investigated expression levels and localizations of AQP3 and AQP8 and their possible functions in the rat digestive system using real-time polymerase chain reactions, western blot analysis and immunohistochemistry. We investigated the expression levels and localizations of AQP3 and AQP8 in esophagus, forestomach, glandular stomach, duodenum, jejunum, ileum, proximal and distal colon, and liver. AQP3 was expressed in the basolateral membranes of stratified epithelia (esophagus and forestomach) and simple columnar epithelia (glandular stomach, ileum, and proximal and distal colon). Expression was particularly abundant in the esophagus, and proximal and distal colon. AQP8 was found in the subapical compartment of columnar epithelial cells of the jejunum, ileum, proximal colon and liver; the most intense staining occurred in the jejunum. Our results suggest that AQP3 and AQP8 play significant roles in intestinal function and/or fluid homeostasis and may be an important subject for future investigation of disorders that involve disruption of intestinal fluid homeostasis, such as inflammatory bowel disease and irritable bowel syndrome.     

Strain-Dependent Effects of Sub-chronically Infused Losartan Against Kainic Acid-Induced Seizures,Oxidative Stress,and Heat Shock Protein 72 Expression

We studied the involvement of angiotensin (Ang) II AT₁ receptors in the pathophysiology of kainate (KA)-induced neurotoxicity, focusing on the regulation of the oxidative stress state and expression of HSP 72 in the frontal cortex and hippocampus in two strains, spontaneously hypertensive rats (SHRs) and normotensive Wistar rats. The KA injection was executed after the rats were infused subcutaneously via osmotic mini-pumps with losartan (10 mg/kg day) for 14 days. Losartan delayed the onset of KA-induced seizures in SHRs but not in Wistar rats without affecting the seizure intensity score. This selective AT₁ receptor antagonist decreased the lipid peroxidation only in naive SHRs. However, it attenuated the KA-induced increase in lipid peroxidation in both SHRs and Wistar rats. The adaptive enhancement of cytosolic superoxide dismutase (SOD) activity in KA-treated SHRs was recovered to control level after sub-chronic losartan infusion while no change in mitochondrial SOD activity was detected in the two strains. Both losartan and KA produced a higher expression of HSP 72 in the hippocampus of the two strains compared to naive rats infused with vehicle. Taken together, our findings demonstrate that the efficacy of a sub-chronic systemic losartan infusion in preventing the KA-induced seizure activity and neurotoxicity is more pronounced in SHRs, considered as a model of essential hypertension, than in normotenisve Wistar rats. The results suggest that the blockade of AT1 receptors, commonly used as a strategy for prevention of high blood pressure, may be useful as an adjunctive treatment in status epilepticus to reduce oxidative stress and neurotoxicity.     

A novel,thermostable manganese-containing superoxide dismutase from <Emphasis Type="Italic">Bacillus licheniformis</Emphasis>

A new, thermostable superoxide dismutase (SOD) from Bacillus licheniformis M20, isolated from Bulgarian mineral springs, was purified 11-fold with 11% recovery of activity. From native PAGE and SDS-PAGE, the enzyme was composed of two subunits of 21.5 kDa each. The SOD was inhibited only by NaN₃, which suggested that this SOD is of the manganese superoxide dismutase type. The purified enzyme had maximum activity at pH 8 and 55°C. The half-life of the SOD was 10 min at 95°C.     

A molecular toolkit for highly insulating tethered bilayer lipid membranes on various substrates

Tethered bilayer lipid membranes (tBLMs) are promising model architectures that mimic the structure and function of natural biomembranes. They provide a fluid, stable, and electrically sealing platform for the study of membrane related processes, specifically, the function of incorporated membrane proteins. This paper presents a generic approach toward the synthesis of functional tBLMs adapted for application to various surfaces. The central element of a tethered membrane consists of a lipid bilayer. Its proximal layer is covalently attached via a spacer unit to a solid support, either gold or silicon oxide. The membranes are characterized optically by using surface plasmon resonance spectroscopy (SPR) or ellipsometry and electrically by using electrochemical impedance spectroscopy (EIS). The bilayer membranes obtained show high electrical barrier properties and can be used to incorporate and study small membrane proteins in a functional form.