Nations within a nation: variations in epidemiological transition across the states of India, 1990–2016 in the Global Burden of Disease Study

18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016

Gastrointestinal Endogenous Protein-Derived Bioactive Peptides: An in Vitro Study of Their Gut Modulatory Potential

A recently proposed paradigm suggests that, like their dietary counterparts, digestion of gastrointestinal endogenous proteins (GEP) may also produce bioactive peptides. With an aim to test this hypothesis, in vitro digests of four GEP namely; trypsin (TRYP), lysozyme (LYS), mucin (MUC), serum albumin (SA) and a dietary protein chicken albumin (CA) were screened for their angiotensin-I converting (ACE-I), renin, platelet-activating factor-acetylhydrolase (PAF-AH) and dipeptidyl peptidase-IV inhibitory (DPP-IV) and antioxidant potential following simulated in vitro gastrointestinal digestion. Further, the resultant small intestinal digests were enriched to obtain peptides between 3–10 kDa in size. All in vitro digests of the four GEP were found to inhibit ACE-I compared to the positive control captopril when assayed at a concentration of 1 mg/mL, while the LYS < 3-kDa permeate fraction inhibited renin by 40% (±1.79%). The LYS < 10-kDa fraction inhibited PAF-AH by 39% (±4.34%), and the SA < 3-kDa fraction inhibited DPP-IV by 45% (±1.24%). The MUC < 3-kDa fraction had an ABTS-inhibition antioxidant activity of 150 (±24.79) µM trolox equivalent and the LYS < 10-kDa fraction inhibited 2,2-Diphenyl-1-picrylhydrazyl (DPPH) by 54% (±1.62%). Moreover, over 190 peptide-sequences were identified from the bioactive GEP fractions. The findings of the present study indicate that GEP are a significant source of bioactive peptides which may influence gut function.The authors acknowledge the financial support provided by the Centre of Research Excellence (CoRE) fund from the Tertiary Education Commission and the Ministry of Education, New Zealand. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)

Gastrointestinal endogenous proteins as a source of bioactive peptides--an in silico study.

Dietary proteins are known to contain bioactive peptides that are released during digestion. Endogenous proteins secreted into the gastrointestinal tract represent a quantitatively greater supply of protein to the gut lumen than those of dietary origin. Many of these endogenous proteins are digested in the gastrointestinal tract but the possibility that these are also a source of bioactive peptides has not been considered. An in silico prediction method was used to test if bioactive peptides could be derived from the gastrointestinal digestion of gut endogenous proteins. Twenty six gut endogenous proteins and seven dietary proteins were evaluated. The peptides present after gastric and intestinal digestion were predicted based on the amino acid sequence of the proteins and the known specificities of the major gastrointestinal proteases. The predicted resultant peptides possessing amino acid sequences identical to those of known bioactive peptides were identified. After gastrointestinal digestion (based on the in silico simulation), the total number of bioactive peptides predicted to be released ranged from 1 (gliadin) to 55 (myosin) for the selected dietary proteins and from 1 (secretin) to 39 (mucin-5AC) for the selected gut endogenous proteins. Within the intact proteins and after simulated gastrointestinal digestion, angiotensin converting enzyme (ACE)-inhibitory peptide sequences were the most frequently observed in both the dietary and endogenous proteins. Among the dietary proteins, after in silico simulated gastrointestinal digestion, myosin was found to have the highest number of ACE-inhibitory peptide sequences (49 peptides), while for the gut endogenous proteins, mucin-5AC had the greatest number of ACE-inhibitory peptide sequences (38 peptides). Gut endogenous proteins may be an important source of bioactive peptides in the gut particularly since gut endogenous proteins represent a quantitatively large and consistent source of protein

Number of potential bioactive peptides (per protein molecule) predicted to be released and A_D¹ value after gastric digestion of both gut endogenous proteins secreted in the mouth and stomach and selected dietary proteins based on an <i>in silico</i> digestion model.

1<p>A_D is the frequency of occurrence of bioactive peptides after digestion of the protein, calculated as where, a_D is the number of identified bioactive peptides present after the simulated (<i>in silico</i>) digestion and N is the total number of amino acid residues within the protein.</p>2<p>2 ACE-inhibitor, 4 stimulating (glucose uptake-, -vasoactive substance release), 6 antioxidative, 8 inhibitor (dipeptidyl peptidase IV inhibitor-, dipeptidyl-aminopeptidase IV inhibitor-, dipeptidyl carboxypeptidase-, CaMPDE-, neuropeptide-), 10 activating ubiquitin mediated proteolysis.</p>3<p>The total number of peptides released is a summation of all the bioactive peptides predicted to be released after digestion of the intact proteins.</p>4<p>Some of the predicted bioactive peptides have more than one activity. Hence, the total number of bioactive peptides released may be less than the summation of the number of bioactive peptides from the individual activity categories.</p

Predicted quantity of bioactive peptides (mg/d) released after digestion of either dietary proteins or gut endogenous proteins in the gastrointestinal tract.

1<p>Estimated based on the predicted total number of bioactive peptides released after gastric and small intestinal digestion (from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0098922#pone-0098922-t004" target="_blank">Table 4</a>), and the moles and molar masses of the respective proteins; and considering that the majority of the predicted bioactive peptides are ‘dipeptides’. All of the evaluated food proteins are used as a model for the remaining proteins in the respective food product.</p>2<p>The model diet is based on a recommended diet for a healthy adult weighing 60 kg, supplying 0.66 g/kg body weight protein per day, amounting to a protein intake of 40 g per day, designed to comply with the FAO recommendations 1]; whereby dairy, wheat, soya products, chicken egg products, chicken meat contribute 4, 14, 3, 6 and 13 g of protein respectively; Protein content of food products estimated based on the United States Department of Agriculture (USDA) Nutrient Data Laboratory database 42].</p>3<p>Calculated based on Moughan, 2011 41], using the amount of gut endogenous protein nitrogen secreted into the gastrointestinal tract, but, excludes protein nitrogen derived from epithelial and bacterial cells.</p

Number of potential bioactive peptides (per protein molecule) predicted to be released and A_D¹ value after gastric plus small intestinal digestion for gut endogenous proteins secreted in the mouth and stomach and selected dietary proteins based on an <i>in silico</i> digestion model.

1<p>A_D value is the frequency of occurrence of bioactive peptides after digestion of the protein, calculated as where, a_D is the number of identified bioactive peptides present after the simulated (<i>in silico</i>) digestion and N is the total number of amino acid residues within the protein.</p>2<p>2 ACE-inhibitor, 4 stimulating (glucose uptake-, -vasoactive substance release), 5 regulating (ion flow-, stomach mucosal membrane activity-), 6 antioxidative, 8 inhibitor (dipeptidyl peptidase IV inhibitor-, dipeptidyl-aminopeptidase IV inhibitor-, dipeptidyl carboxypeptidase-, CaMPDE-, neuropeptide-), 9 hypotensive, 10 activating ubiquitin mediated proteolysis.</p>3<p>The total number of peptides released is a summation of all the bioactive peptides predicted to be released after digestion of the intact proteins.</p>4<p>Some of the predicted bioactive peptides have more than one activity. Hence the total number of bioactive peptides released may be less than the summation of the number of bioactive peptides from the individual activity categories.</p

Gut endogenous and dietary proteins examined in the <i>in silico</i> study¹.

1<p>Compiled from the UniProtKB Protein Database <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0098922#pone.0098922-TheUniProt1" target="_blank">[25]</a>.</p>2<p>The given chain length excludes signal peptide.</p>3<p>Initiator methionine not removed from the intact protein sequence (chain length inclusive of the initiator methionine).</p

Number of potential bioactive peptides (per protein molecule) predicted to be released and A_D¹ value after small intestinal digestion for gut endogenous proteins secreted in the small intestine based on an <i>in silico</i> digestion model.

1<p>A_D value is the frequency of occurrence of bioactive peptides after digestion of the protein, calculated as where, a_D is the number of identified bioactive peptides present after the simulated (<i>in silico</i>) digestion and N is the total number of amino acid residues within the protein.</p>2<p>2 ACE-inhibitor, 5 regulating (ion flow-, stomach mucosal membrane activity-, phosphoinositol mechanism peptide-), 6 antioxidative, 8 inhibitor (dipeptidyl peptidase IV inhibitor-, dipeptidyl-aminopeptidase IV inhibitor-, dipeptidyl carboxypeptidase-, CaMPDE-, neuropeptide-), 9 hypotensive.</p>3<p>The total number of peptides released is a summation of all the bioactive peptides predicted to be released after digestion of the intact proteins.</p>4<p>Some of the predicted bioactive peptides have more than one activity. Hence the total number of bioactive peptides released may be less than the summation of the number of bioactive peptides from the individual activity categories.</p>5<p>Pancreatic triacylglycerol is predicted to release 1 immunostimulating peptide. Peptide not shown in the table, but is reflected in the corresponding total number of predicted bioactive peptides released.</p

Number (#) of potential bioactive peptides (per protein molecule) identified in the intact endogenous and dietary proteins and the A_O¹ and Y² values.

1<p>A_O is the frequency of occurrence of bioactive fragments in a protein sequence, calculated as where, a_O is the total number of identified bioactive peptides present in the protein or the number of bioactive peptides with a specific activity based on the BIOPEP database <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0098922#pone.0098922-ChairofFood1" target="_blank">[22]</a>, N is the total number of amino acid residues within the protein.</p>2<p>Y is the relative frequency of occurrence of bioactive fragments with a specific activity in a protein sequence, calculated as </p><p>where, Aoj is the number of peptides with a specific activity, l is the total number of peptide sequences across all activity categories present within the protein, j is the specified activity.</p>3<p>1 antiamnestic, 2 ACE-inhibitor, 3 antithrombotic, 4 stimulating (glucose uptake-, -vasoactive substance release), 5 regulating (ion flow-, stomach mucosal membrane activity-, phosphoinositol mechanism peptide-), 6 antioxidative, 7 bacterial permease ligand, 8 inhibitor (dipeptidyl peptidase IV inhibitor-, dipeptidyl-aminopeptidase IV inhibitor-, dipeptidyl carboxypeptidase-, CaMPDE-, neuropeptide-), 9 hypotensive, 10 activating ubiquitin mediated proteolysis.</p>4<p>Overall A_O represents the total number of amino acid sequences corresponding to known bioactive peptides identified per protein molecule across all bioactivity categories normalised for amino acid chain length.</p>5<p>The total number of bioactive peptides represents the total number of amino acid sequences corresponding to known bioactive peptides identified per protein molecule across all bioactivity categories (not just the 10 bioactivity categories shown above).</p

Amino acid¹ sequences of bioactive peptides predicted to be released after mouth to ileum digestion of selected proteins based on an <i>in silico</i> digestion model.

1<p>All amino acids are denoted using ‘the one-letter notation for amino acid sequences’ from the International Union of Pure and Applied Biochemistry and International Union of Biochemistry, 1971: Alanine = A; Arginine = R; Asparagine = N; Aspartic acid = D; Cysteine = C; Glutamic acid = E; Glutamine = Q; Glutamine or Glutamic acid = Z; Glycine = G; Histidine = H; Isoleucine = I; Leucine = L; Lysine = K; Methionine = M; Phenylalanine = F; Proline = P; Serine = S; Threonine = T; Tryptophan = W; Tyrosine = Y; Valine = V.</p>2<p>2 ACE-inhibitor, 4 stimulating (glucose uptake-, -vasoactive substance release), 6- antioxidative, 8 inhibitor (dipeptidyl peptidase IV inhibitor-, dipeptidyl-aminopeptidase IV inhibitor-, dipeptidyl carboxypeptidase-, CaMPDE-, neuropeptide-), 9 hypotensive.</p