Homo medicus: The transition to meat eating, increased pathogen pressure, and the constitutive and inducible use of pharmacological plants in Homo

The human lineage entered a more carnivorous niche 2.6 mya. A range of evidence indicates this increased zoonotic pathogen pressure. This evidence includes increased zoonotic infections modern hunter-gatherers and bushmeat hunters relative to others living in the same environments, exceptionally low stomach pH compared to other primates, human-specific downregulation in ANTXR2 that would have protected against increased exposure to zoonotic anthrax, exceptional human immune responses to LPS compared to other primates, and other divergent immune genes. These all point to change, and likely intensification, in the disease environment of Homo compared to earlier hominins and other apes. At the same time, the brain, an organ in which inflammatory immune responses are highly constrained, begins to increase, eventually tripling in size. We propose that the combination of increased zoonotic pathogen pressure and the challenges of defending a large brain and body from pathogens across what would eventually become the longest lifespan of any mammal, selected for intensification of the self-medication strategies already in place in apes and other primates, resulting in a variety of plant-based pathogen defenses. In support, there is evidence of medicinal plant use by hominins in the middle Paleolithic, and all cultures today have sophisticated, plant-based medical systems, incorporate plant components high in secondary compounds (spices) into food, and regularly consume psychoactive substances that are harmful to helminths and other pathogens in the CNS and other tissues. The computational challenges of discovering effective plant-based treatments, and the economic challenges of benefiting from costly-to- acquire medical knowledge that would be more often useful to others than oneself, were selection pressures for increased cognitive abilities and unique exchange relationships in Homo. In the story of human evolution, which has long featured hunters, shamans and healers had an equal role to play.

Application of Creep Feed and Phytase Super-Dosing as Tools to Support Digestive Adaption and Feed Efficiency in Piglets at Weaning

A total of 64 piglets were used in a 35-day study to evaluate whether creep feeding piglets on the sow or super-dosing phytase to piglets post-weaning can be used as a tool to reduce stress and support adaption to weaning. Treatments consisted of creep or no creep feed being offered pre-weaning and with or without phytase supplementation at 2000 FTU/kg post-weaning. Blood samples were collected from eight piglets per treatment on days 0 (weaning), 7 and 21 post-weaning to determine plasma cortisol and myo-inositol concentrations. Four piglets per treatment (n = 16) were administered Heidelberg pH capsules 1 week prior to weaning, on the day of weaning, as well as 7 days and 21 days post-weaning, with readings monitored over a 3 h period. In the first week post-weaning, creep-fed piglets had higher daily gains (0.23 vs. 0.14 kg/d, p < 0.05) and a lower feed conversion ratio (FCR, 0.99 vs. 1.35, p < 0.01), compared to non-creep-fed pigs. At 21 days post-weaning, irrespective of creep feed, phytase supplementation reduced FCR (1.10 vs. 1.18, p = 0.05) of piglets. Average real-time stomach pH was lower in creep-fed piglets at 1 week prior to weaning (pH 3.2 vs. 4.6, p < 0.001) and on day of weaning (pH 3.1 vs. 3.7, p < 0.01). Following weaning, phytase reduced average stomach pH of piglets at days 7 (pH 2.6 vs. 3.3, p < 0.001) and 21 (pH 2.2 vs. 2.6, p < 0.01). Both cortisol and myo-inositol concentrations in plasma decreased with age; however, cortisol levels were unaffected by either treatment. Plasma myo-inositol concentrations were higher in creep-fed piglets at day of weaning (p < 0.05) and with phytase super-dosing on day 21 (p < 0.001). These findings demonstrate that both creep feeding and phytase super-dosing are useful practices to encourage better adaption to weaning and support piglet performance. This response was not related to reduced stress in piglets, as determined by cortisol levels, but instead appears to relate to improved gastric conditions for digestion, phytate degradation and myo-inositol provision in piglets.

Reduced concentrations of limestone and monocalcium phosphate in diets without or with microbial phytase did not influence gastric pH, fecal score, or growth performance, but reduced bone ash and serum albumin in weanling pigs

An experiment was conducted to test the hypothesis that reducing limestone and monocalcium phosphate in diets for weanling pigs by lowering the concentration of Ca and P or by including microbial phytase in the diet will reduce stomach pH and fecal score and will improve growth performance of pigs. A total of 160 weanling pigs (5.75 ± 1.04 kg) were allotted to 4 corn-soybean meal-based diets in a completely randomized design with 5 pigs per pen. Diets for phase 1 (d 1 to 15) were formulated using a 2 × 2 factorial design with 2 concentrations of Ca and P (adequate or deficient levels of total Ca and digestible P) and 2 inclusion levels of phytase (0 or 2,000 units/kg feed). Phytase was assumed to release 0.16% total Ca and 0.11% digestible P. Common diets were fed in phases 2 (d 16 to 21) and 3 (d 22 to 35). Fecal scores were recorded in phase 1 and on d 15, gastric pH was measured and a blood sample and the right femur were collected from 1 pig per pen. Growth performance data were recorded within each phase. Results indicated that in phase 1, at deficient dietary Ca and P, pigs fed the diet with phytase had greater (P &lt; 0.05) average daily gain (ADG) and gain to feed (G:F) compared with pigs fed the diet without phytase, but in diets with adequate levels of Ca and P, no effect of phytase inclusion was observed (interaction, P &lt; 0.05). Without phytase, pigs fed the diet with deficient Ca and P had reduced (P &lt; 0.05) G:F compared with pigs fed the diet with adequate Ca and P, but if phytase was included, there was no effect of Ca and P on G:F (interaction, P &lt; 0.05). For phases 2 and 3, and from d 1 to 35, no differences among dietary treatments were observed for ADG or G:F. Bone ash was greater (P &lt; 0.05) in pigs fed diets with adequate Ca and P than in pigs fed diets with deficient Ca and P, but no effect of phytase inclusion was observed on bone ash. Concentrations of Ca and P did not affect stomach pH or fecal score, but pigs fed diets with phytase tended (P &lt; 0.10) to have reduced stomach pH and fecal score compared with pigs fed diets without phytase. Pigs fed diets with adequate Ca and P had greater (P &lt; 0.05) albumin in serum than pigs fed the Ca- and P-deficient diets. In conclusion, phytase inclusion in phase 1 diets may reduce diarrhea, but lowering Ca and P does not reduce stomach pH or fecal score and decreases bone ash, although growth performance during the entire weanling period is not affected.

A bacteriophage cocktail significantly reduces Listeria monocytogenes without deleterious impact on the commensal gut microbiota under simulated gastro-intestinal conditions

In this study, we examined the effect of a bacteriophage cocktail (tentatively designated FOP, for Foodborne Outbreak Pill) on the levels of Listeria monocytogenes in simulated small intestine, large intestine, and Caco-2 model systems. We found that FOP survival during simulated passage of the upper gastrointestinal was dependent on stomach pH, and that FOP robustly inhibited L. monocytogenes levels with effectiveness comparable to antibiotic treatment (ampicillin) under simulated ilium and colon conditions. FOP did not inhibit the commensal bacteria, whereas ampicillin treatment led to dysbiosis-like conditions. FOP was also more effective than antibiotic in protecting Caco-2 cells from adhesion and invasion by L. monocytogenes, while not triggering an inflammatory response. Our data suggest that FOP may provide a robust protection against L. monocytogenes should the bacterium enter the human gastrointestinal tract (e.g., by consumption of contaminated food), without deleterious impact on the commensal bacteria.

Effect of dietary folate level on organ weight, digesta pH, short-chain fatty acid concentration, and intestinal microbiota of weaned piglets

Folate is increasingly thought to promote gastrointestinal health and regulate the diversity of gut microbiota to alleviate weaning stress in piglets. The present study was conducted to investigate the effects of folate on organ weight, digesta pH, short-chain fatty acids (SCFAs) concentration, and intestinal microbiota in weaned piglets. A total of 28 piglets (6.73 ± 0.62 kg) were allocated to four dietary treatments consisting of a control group, 3, 9, and 18 mg/kg of folate supplementation in a 14-d feeding trial. The results showed that piglets fed with 9 and 18 mg/kg of folate supplementation had greater (P &lt; 0.05) average liver and spleen weight than the control group. Folate supplementation (9 and 18 mg/kg) can significantly increase (P &lt; 0.05) the stomach pH and tend (P &lt; 0.10) to decrease the cecum pH. Folate treatment (9 and 18 mg/kg) had a positive effect on the metabolism of SCFAs in piglets, in particular, compared with the control group, and the content of acetic acid (AA) and valeric acid was markedly increased (P &lt; 0.05) in the cecum and colon, respectively. Moreover, isobutyric acid, butyric acid, and isovaleric acid were tended (P &lt; 0.10) to increase in the colon. Cecum contents samples were used to determine bacterial community diversity by 16S rRNA gene amplicon sequencing. At the genus level, in the cecum, there was a higher (P &lt; 0.05) relative abundance of Lactobacillus reuteri, Lactobacillus salivarius, and Lactobacillus mucosae in the 9 mg/kg folate supplementation group. The functional pathways analysis predicted that folate may modify nutrient metabolism by changing the gut microbiota function of weaned piglets. Furthermore, the data showed that Lactobacillus was positively correlated with AA in the cecum. Overall, these findings suggested that folate treatment could increase the organ weight and the stomach pH of weaned piglets and had beneficial effects on gut health, which might be attributed to the alteration in intestinal microbiota induced by folate and the interaction of the intestinal microbiota with SCFAs.

Three-decade failure to eradication of refractory Helicobacter pylori infec-tion and recent efforts to eradicate the infection

Background: Helicobacter pylori causes dangerous and deadly diseases such as gastric cancer and duodenal ulcers. Eradication and treatment of this bacterium are very important due to the deadly diseases caused by H. pylori and the high cost of treatment for countries. So, we present a complete list of the most important causes of failure in the treatment and eradication of H. pylori, and addresses new therapeutic methods that may be effective in controlling this bacterium in the future. Results: Many efforts have been made to control and eradicate this bacterium over the years, but no success has been achieved since its eradication is a complex process affected by the bacterial properties and host factors. Previous studies have shown that various factors are involved in failure to eradicate H. pylori, such as new genotypes of the bacterium with higher pathogenicity, inappropriate patient cooperation, mutations, biofilm formation and dormant forms that cause antibiotic resistance, acidic stomach pH, high bacterial load, smoking, immunosuppressive features and intracellular occurrence of H. pylori. On the other hand, recent studies reported that the use of probiotics, nanoparticles, antimicrobial peptides, natural product and vaccine can be helpful in the treatment and eradication of H. pylori infections. Conclusion: Eradication of H. pylori is crucial for the treatment of important diseases such as gastric cancer. Therefore, it seems that identifying the failure causes of treating this bacterium can be helpful in controlling the infections. Besides, further studies on new therapeutic strategies may help eradicate H. pylori in the future.

Systemic analysis of tissue cells potentially vulnerable to SARS-CoV-2 infection by the protein-proofed single-cell RNA profiling of ACE2, TMPRSS2 and Furin proteases

ABSTRACTSingle-cell RNA profiling of ACE2, the SARS-CoV-2 receptor, had proposed multiple tissue cells as the potential targets of SARS-CoV-2, the novel coronavirus causing the COVID-19 pandemic. However, most were not echoed by the patients’ clinical manifestations, largely due to the lack of protein expression information of ACE2 and co-factors. Here, we incorporated the protein information to analyse the expression of ACE2, together with TMPRSS2 and Furin, two proteases assisting SARS-CoV-2 infection, at single cell level in situ, which we called protein-proofed single-cell RNA (pscRNA) profiling. Systemic analysis across 36 tissues revealed a rank list of candidate cells potentially vulnerable to SARS-CoV-2. The top targets are lung AT2 cells and macrophages, then cardiomyocytes and adrenal gland stromal cells, followed by stromal cells in testis, ovary and thyroid. Whereas, the polarized kidney proximal tubule cells, liver cholangiocytes and intestinal enterocytes are less likely to be the primary SARS-CoV-2 targets as ACE2 localizes at the apical region of cells, where the viruses may not readily reach. Actually, the stomach may constitute a physical barrier against SARS-CoV-2 as the acidic environment in normal stomach (pH < 2.0) could completely inactivate SARS-CoV-2 pseudo-viruses. These findings are in concert with the clinical characteristics of prominent lung symptoms, frequent heart injury, and uncommon intestinal symptoms and acute kidney injury. Together, we provide a comprehensive view on the potential SARS-CoV-2 targets by pscRNA profiling, and propose that, in addition to acute respiratory distress syndrome, attentions should also be paid to the potential injuries in cardiovascular, endocrine and reproductive systems during the treatment of COVID-19 patients.

Metallic iron in cornflakes

Magnetometry and X-ray analysis show that the iron in cornflake-style cereals fortified with this essential element at levels up to 14 mg per 100 g, is micron-sized body-centred cubic metallic iron, partially soluble at stomach pH.

Development and validation of RP-HPLC method for stability evaluation of model hydrazone, containing a pyrrole ring

RP-HPLC method with UV detection was developed and validated for determination of the chemical stability and stability in close to physiological conditions of a model pyrrole hydrazone ethyl 5-(4-bromophenyl)-1-(1-(2-(4-hydroxy-3-methoxybenzylidene) hydrazineyl)-4-methyl-1-oxopentan-2-yl)-2-methyl-1H-pyrrole-3-carboxylate (D_5d), containing susceptible to hydrolysis hydrazone group. The evaluated substance was subjected to the influence of a variety of pH , representing the main physiological values of 37°C and corresponding pH values in the stomach (pH 2.0), blood (pH 7.4) and small intestine (pH 9.0). Chemical stability in a highly alkaline medium with a pH of 13.0 was also evaluated. The hydrazone I tested was found to be stable at pH 7.4 and pH 9.0 and 37 ° C and hydrolyzed under strong acidic (pH 2.0) and highly alkaline media (pH 13.0) and at the same temperature.The products of hydrolysis were identified to be the initial hydrazide and aldehyde, pointing the hydrazone group as most liable.