Acid Suppression Research Articles

Saccharomyces cerevisiae strains L7 contribute to flavor and deacidification in Suanyu, a Chinese traditional fermented fish

Saccharomyces cerevisiae L7 was found to be an excellent starter and biological deacidification strain for Suanyu, however, the underlying mechanisms remain poorly understood. This study aimed to investigate the acid inhibition mechanism of S. cerevisiae L7. The strain enhances the sensory and flavor characteristics of Suanyu. The growth of Lactiplantibacillus plantarum is inhibited due to competition for carbon sources, resulting in a decrease in cell count from 9.00 Lg CFU/mL at 48 h to 7.70 Lg CFU/mL in co-culture. The addition of yeast reduces acidity, decreasing it from 5.83 g/kg to 0.82 g/kg at 48 h, while increasing sugar utilization to 94.52%. We found that cell contact was the main method of inhibition between the two microbials. Transcriptome analysis revealed that multiple pathways were affected under co-culture, ultimately leading to a decrease in lactic acid production. These findings provide valuable insights into the microbial interactions involved in biological deacidification.

Changes in antioxidants and nutritional properties during germination of soybean

Soybeans are a valuable source of nutrients and bioactive compounds. However, their nutritional quality can be limited by the presence of antinutrients, such as phytic acid and trypsin inhibitors. Germination is a natural process that can enhance the nutritional value of legumes by reducing antinutrients and increasing the bioavailability of nutrients. The objective of this study was to evaluate the effect of soaking and germination on the antioxidant and nutritional attributes of soybean. Results showed that the germination process led to a significant increase (p ≤ 0.05) in the content of phenolic, flavonoids, and antioxidat activity (%) compounds following the 72-hour germination compared to samples from ungerminated soybeans. Strong correlations were concluded between antioxidant activity and total phenolic (R2 0.92), flavonoids (R2 0.82), and ascorbic acid (R2 0.99). The germination process also enhanced proteases activities, lipase activity, and protein digestibility. Concurrently, there was a significant reduction in phytic acid from 99.20 ± 2.56 to 73.39 ± 0.85, mg/100 g as well as trypsin inhibitors from 5.73 ± 0.116 to 2.91 ± 0.126 mg/g. Germination led to these alterations contributed to an enhancement in the antioxidant and nutritional characteristics of soybean.

Sequential bioaugmentation of the dominant microorganisms to improve the fermentation and flavor of cereal vinegar

Traditional cereal vinegars are fermented by microorganisms that are spontaneously enriched, leading to uncertainty in regulating the fermentation process and flavor. The objective of this study was to elucidate the impact of the predominant microorganisms, provenly Lactobacillus helveticus and Acetobacter pasteurianus, on the solid-state fermentation (SSF) and flavor profile of cereal vinegar by several bioaugmentation strategies. The results indicated that the sequential bioaugmentation of predominant microorganisms improved the utilization of raw material and most key flavor compounds. Through sequential bioaugmentation strategy, bacterial diversity was regulated due to minimizing acetic acid inhibition in the early stages, and the non-volatile acid was targetedly improved by Lactobacillus. Furthermore, the important flavor of non-volatile acid, esters, acetoin, and tetramethyl-pyrazine content was enhanced by sequential bioaugmentation. Therefore, the sensory score on taste and odor were improved. These results provide a reference for the targeted regulation of the SSF and the flavor quality of cereal vinegar.

Pharmacodynamics of 2 dosages of orally administered esomeprazole in client-owned, healthy dogs: A prospective, crossover study.

Esomeprazole use is increasing in dogs, but the gastrointestinal adverse events associated with q12h dosing necessitate pharmacodynamic evaluation of a reduced dose and frequency of administration. To compare the efficacy of 2 doses of (q24h) esomeprazole in raising intragastric pH in dogs. Nine healthy, client-owned dogs, >20 kg. Prospective, randomized, double blinded, crossover study. Esomeprazole (0.5 or 1 mg/kg q24h) was orally administered for up to 5 days per treatment arm, and the mean percentage time intragastric pH was ≥3 (MPT3) and ≥4 (MPT4) for 24 hours periods were compared to pretreatment pH using a continuous pH monitoring system. Dogs failing to reach pH goals (MPT3 ≥75%, MPT4 ≥66%) with once daily dosing received esomeprazole 1 mg/kg PO q12h to determine if a higher dose would improve acid suppression. No significant difference in the MPT3 or MPT4 was identified between treatments for any time point (P > .05). Both doses increased the MPT pH ≥3 and 4 median [range] (0.5 mg/kg, 1 mg/kg) on days 1 (MPT3: 76.8% [44-100], 69.2% [28.2-100]; MPT4: 65.6% [16.7-99.3], 54.9% [14.9-93.3]; P = .0009) and 2 (MPT3:77.2% [27.4-100], 75.4% [49.4-89.5]; MPT4: 66.3% [15.5-100], 59.7% [33.8-81.2]; P = .0005) of PPI treatment compared to pretreatment (MPT3: 58.3% [0.02-93.9], 52.6% [6.1-94.7]; MPT4: 25.2% [0-86.8], 32.4% [1.8-89.3]). Six dogs (66%, [0.36, 0.97]) reached pH goals established in humans with q24h dosing. Both q24h PO esomeprazole doses were effective in raising intragastric pH, despite high intersubject variability, but 33% of dogs required q12h dosing to reach pH goals.

A novel alkali and thermotolerant protease from Aeromonas spp. retrieved from wastewater

Enzymes are integral to numerous industrial processes, with a growing global demand for various enzyme types. Protease enzymes, in particular, have proven to be cost-effective, stable, and compatible alternatives to traditional chemical processes in both industrial and environmental applications. In this study, an alkaline protease-producing strain of Aeromonas spp. was isolated from a wastewater treatment plant in Iran. The protease production was confirmed by culturing the strain on casein agar medium. The bacterium was identified through morphological, biochemical, and 16 S rRNA sequencing analyses. The optimal culture medium for bacterial growth and enzyme production was obtained using peptone, salt, yeast extract, galactose, and CaCl₂ at an initial pH of 8. Maximum protease production was achieved after 20 h of incubation at 40 °C. To partially purify the enzyme, the supernatant of the bacterial culture medium was first centrifuged, and the enzyme was precipitated using ammonium sulfate, followed by dialysis. Zymography revealed the production of one type of protease during bacterial growth. The partially purified protease exhibited optimal activity at pH 8.5 and maximum stability at pH 9. The optimum temperature for maximum enzyme activity was observed at 50 °C, with 100% residual activity retained for 1 h at 0 °C. The effect of metal ions on enzyme activity was assessed, revealing that KCl induced the most significant effects (p < 0.0001) on enzyme activity. Chemical amino acid modifiers and inhibitors, such as EDTA, DEPSI, and IAA, did not exhibit significant inhibition. In contrast, PMSF and HNBB significantly (p < 0.0001) reduced enzyme activity, suggesting that the enzyme could be classified as a serine protease. The protease also demonstrated high stability in the presence of 2% SDS, showing no signs inactivation. The alkaline pH optimum, thermal stability, and resistance to SDS exhibited by the protease produced by the Aeromonas strain are particularly promising characteristics that warrant further investigation. Based on preliminary tests and the enzyme’s characteristics, this protease can be recommended for various applications, pending further studies.

Comparative characteristics of the blood cytokine profile in gastritis in schoolchildren with a family predisposition to gastric cancer and peptic ulcer

The formation of diseases of the gastric and duodenum in the adult population begins at school age. Among the leading risk factors for their formation are family predisposition (to peptic ulcer disease (PU), gastric cancer). The basis for their formation is gastritis, the course of which is actively influenced by cytokines. Aim. To study the characteristics of cytokine levels in blood serum in schoolchildren with gastritis and a family history of gastric cancer and peptic ulcer. A total of 179 schoolchildren with gastroenterological complaints were examined. All subjects underwent an endoscopic examination with biopsies taken from the antrum of the gastric and morphological confirmation of gastritis (Sydney classification). The presence of H. pylori was also determined by morphological method. The level of cytokines in the blood (IL-2, IL-4, IL-8, IL-18, IL- 1β, IFNα, TNFα) was determined by ELISA. The study found that schoolchildren with a burden of ulcer had a decreased IL-1β in comparison with children without aggravation (p = 0.005), and with children with a burden of cancer (p = 0.030). Also, IFNα was increased in schoolchildren with a burden of ulcerative disease (p = 0.001) and gastric cancer (p = 0.038). A decrease in IL-1β was found in children with aggravated ulcer disease, both with H. pylori infection (p = 0.048) and without it (p = 0.043). IL-1β plays an important role in the immune response to H. pylori infection. In addition, it is known that during H. pylori infection the level of IL-1β increases, which is accompanied by inhibition of gastric acidity. There was a decrease in IL-1β and an increase in IFNα in children with aggravated ulcer disease, regardless of the activity of inflammation. In addition, they observed an increase in TNFα (p = 0.04) with high gastritis activity (stage 2-3). In addition, in children with ulcer burden and high gastritis activity, IL-4 is increased (p = 0.018). Thus, in children with a family history of both peptic ulcers and gastric cancer, there are features of the association of specific cytokines with gastritis, as well as its activity and H. pylori infection.

Revolutionizing Influenza Treatment: A Deep Dive into Targeted Drug Delivery Systems.

Influenza, a highly transmissible respiratory infection caused by influenza viruses A and B, poses a persistent threat to global public health due to its high mutation rate, ability to develop resistance to existing antiviral drugs, and capacity for rapid spread. Current treatment options, including four main classes of antiviral agents-adamantanes, neuraminidase inhibitors, RNA-dependent RNA polymerase inhibitors, and polymerase acidic endonuclease inhibitors- are limited by the emergence of drug-resistant viral strains, non-specific drug distribution, and adverse side effects. Moreover, the effectiveness of traditional vaccines is often compromised by antigenic drift and shift, necessitating the development of alternative therapeutic strategies. This review comprehensively explores the potential of novel targeted drug delivery systems to address these limitations and improve influenza management. Nanotechnology-based platforms, including lipid-based, polymer-based, inorganic, and hybrid nanoparticles, offer enhanced drug delivery through improved bioavailability, targeted action, and controlled release, thus minimizing systemic toxicity and optimizing therapeutic outcomes. Inhalation delivery systems such as dry powder inhalers (DPIs), nebulizers, and nanotechnology-based inhalation formulations provide direct delivery of antiviral agents to the respiratory tract, ensuring rapid onset of action with reduced systemic side effects. Transdermal delivery methods, including microneedle patches and hydrogel-based systems, offer non-invasive alternatives that enhance patient compliance and allow for sustained drug release. Furthermore, this review discusses recent innovations, such as responsive drug delivery systems and multifunctional nanoparticles capable of simultaneous delivery of multiple therapeutic agents, representing a significant advancement in the fight against influenza. These novel approaches promise improved targeting and efficacy and enable personalized treatment strategies, enhancing patient outcomes in both seasonal flu and pandemic scenarios. Integrating these advanced drug delivery systems into clinical practice could revolutionize the management of influenza, offering a promising pathway toward more effective and safer therapies.

Cerebral net uptake of lactate contributes to neurological injury after experimental cardiac arrest in rabbits

During focal ischemia, neurons can use lactate as an alternative source of energy through its oxidation into pyruvate by the lactate dehydrogenase (LDH). After cardiac arrest, the neurological consequences of this phenomenon are unknown. Experimental study. Experimental laboratory. Male New-Zealand rabbits. Animals were surgically instrumented and randomly divided into five groups receiving short infusion duration of either lactate or pyruvate or a pre-cardiac arrest infusion of oxamate (an inhibitor of the lactate dehydrogenase) or injection of fluorocitrate (an inhibitor of astrocytic tricarboxylic acid), or Saline (lactate, pyruvate, Oxa, FC and Control groups, respectively). After randomization, animals were submitted to 10 min of ventricular fibrillation and subsequent resuscitation. All animals were then either followed during 4 h, for the evaluation of the cerebral net uptake and concentrations of metabolites by microdialysis (n = 6 in each experimental group, n = 12 in control group), or during 48 h for the evaluation of their neurological outcome (n = 7 in each groups and n = 14 in control group). Cardiac arrest was associated with a dramatic increase in cerebral net uptake of lactate during 120 min after resuscitation, which was increased by lactate or pyruvate administration. This was associated with an increase in the mean neurological dysfunction score (66.7 ± 4.7, 79.0 ± 4.5 vs 57.7 ± 1.5 in Lactate, Pyruvate and Control group respectively) at 48 h after cardiac arrest. Oxamate and FC administration were associated with a lower lactate cerebral uptake after cardiac arrest and with an improvement of the neurological recovery (28.85 ± 9.4, 23.86 ± 6.2 vs 57.7 ± 1.5 in Oxa, FC and Control group respectively). After cardiac arrest, immediate isotonic lactate or pyruvate administration is deleterious. Pre-cardiac arrest LDH inhibition was potently neuroprotective in this setting.

Update Motility Disorders: Gastro-Oesophageal Reflux Disease – Diagnostic and Conservative Approach

Background: Gastro-oesophageal reflux disease (GORD) is extremely common, with at least 1 in 10 people in the general population reporting heartburn and acid regurgitation on a weekly basis. GORD can also be associated with a variety of atypical symptoms, including chest pain, chronic cough, and laryngopharyngeal symptoms. The causes of GORD are multifactorial, and the severity of symptoms is influenced by peripheral and central factors, including psychosocial stress and anxiety. Therefore, for a variety of reasons, no single investigation provides a definitive diagnosis, and standard treatment with acid suppressants is not always effective. Summary: This review introduces the Lyon Consensus, now in its second iteration, a classification system that provides a “conclusive” positive or negative diagnosis of GORD by integrating the results of endoscopy, ambulatory reflux monitoring, and high-resolution manometry. Different algorithms are applied to patients with high and low pre-test probability of a causal relationship between reflux episodes and patient symptoms. The results of these studies identify patients with “actionable” results that require escalation, revision, or discontinuation of GORD treatment. Guidance is provided on the range of conservative treatments available for GORD, including dietary and lifestyle advice, antacids and alginates, and drugs that suppress acid secretion. Key Messages: GORD is a common disorder; however, the causes of reflux and symptoms can be complex. As a result, the diagnosis can be missed, and management is sometimes challenging, especially for patients with atypical symptoms. The Lyon classification establishes a conclusive diagnosis of GORD, based on results of endoscopic and physiological investigation. Typical symptoms usually respond to empiric use of alginate-antacid preparations and acid suppression; however, the management of treatment refractory symptoms is tailored to the individual.

Evaluation of the synergic effect of amino acids for CO2 hydrate formation and dissociation

Gas hydrate formation is a very challenging problem in the oil and gas industry. The chemical inhibition method is the best practicable hydrate mitigation method by injecting hydrate inhibitors such as Thermodynamic Hydrate Inhibitors (THIs) and Kinetic Hydrate Inhibitors (KHIs) into the pipeline. However, the hydrate inhibitors' biodegradability and limited data on dual functional inhibitor mixtures raise concerns in this study. This study aims to investigate and compare thermodynamic and kinetic inhibition on CO2 hydrate by using biodegradable amino acid inhibitor mixtures of Glycine and Alanine. In this study, the inhibitor mixtures were prepared by mixing Glycine and Alanine in 3 different mixture ratios, followed by the Thermodynamic and Kinetic inhibition tests. Thermodynamic Inhibition Test was conducted by using 10 wt% of inhibitor mixtures in a CO2-water system under pressure of 4.0, 3.5, 3.0 and 2.5 MPa, while Kinetic Inhibition Test was carried out by using 1 wt% of the sample in the CO2-water system at a constant pressure of 4.0 MPa and temperatures at 274.15K. The analysis methods for the Thermodynamic Inhibition Test were Hydrate Liquid-Vapor Equilibrium (HLVE) Curve, Average Depression Temperature and Molar Dissociation Enthalpy, while the Induction Time method, the number of CO2 moles consumed, the formation rate of CO2 gas hydrate and RIP were used in the Kinetic Inhibition Test. In this study, all inhibitor mixtures exhibit dual functional inhibition on the CO2 hydrate. For THI, 50% Gly: 50% Ala shows the best thermodynamic inhibition strength with an average depression temperature of 2.42 K. All the inhibitor mixtures for THI have the dissociation enthalpies within the CO2 hydrate enthalpy range, which show that the inhibition is due to the influence on the water molecules’ interaction only. For KHI, 75% Gly: 25% Ala shows the highest kinetic inhibition strength on CO2 formation with the longest induction time of 115.2 min and the highest RIP of 0.40. In the KHI experiment, there is a drop in the CO2 uptake capacity with the presence of inhibitors used, where the highest difference of CO2 moles consumed is 0.0057 mol. A synergistic effect of inhibitor mixtures was observed in this study on 50% Gly: 50% Ala for THI and 75% Gly: 25% Ala for KHI. However, the “degradation” effect was also exhibited on 75% Gly: 25% Ala and 25% Gly: 75% Ala for THI and 50% Gly: 50% Ala and 25% Gly: 75% Ala for KHI, where the performance of the inhibitor mixtures is poorer than the concentrated amino acids. The “degradation” effect of the inhibitor mixtures at certain ratios was not covered in this study and it requires a further understanding of the chemistry behind the inhibition mechanism.

Infection prevention in home dialysis

Purpose of review Among patients with kidney failure, home dialysis modalities, including peritoneal dialysis (PD) and home hemodialysis (HHD) provide several individual and healthcare system benefits over in-center hemodialysis (HD). Infection remains a major source of morbidity and mortality in this population, and a core outcome of critical importance to patients, caregivers, and kidney health professionals. This narrative review provides evidence-based measures for infection prevention among individuals receiving home dialysis, with a particular emphasis on dialysis and access-related infections. Recent findings Patient and care partner education and training is an important and major theme for infection prevention in home dialysis. In PD, identifying and managing modifiable risk factors for infections such as hypokalemia, constipation, use of gastric acid suppressants, and domestic pets, along with the use of antimicrobial prophylaxis, when indicated, can substantially reduce peritonitis risk. Reducing the use of central venous catheters (CVC), and duration of CVC dependence is the most effective means of prevention of HD access-related bloodstream infections in individuals receiving HHD. For arteriovenous fistula cannulation, rope ladder technique is associated with lower risk of infection compared to buttonhole cannulation. Summary Developing and instituting a well structured and evidence-based patient training and education program within home dialysis units is the most important measure in preventing and reducing dialysis and access-related infections. Kidney care providers should be familiar with different infection risk factors among individuals receiving home dialysis.

Unraveling Lipase’s Promiscuous Behavior: Insights into Organic Acid Inhibition during Solventless Ester Production

Unraveling Lipase’s Promiscuous Behavior: Insights into Organic Acid Inhibition during Solventless Ester Production

Lysozyme coupling protease pretreatment to relieve the humic acid inhibition on excess sludge anaerobic fermentation

The asynchronous dosed protease and lysozyme combination pretreatment was proved to be effective in enhancing the anaerobic fermentation of waste activated sludge (WAS). However, humic acid (HA) in the sludge could interact with hydrolase and restrain the hydrolysis efficiency, thus inhibiting short-chain fatty acids (SCFAs) production. This study investigated the effectiveness and mechanism of enzymatic pretreatment against HA. Results showed that the enzyme cocktail method increased the extracellular bioavailable contents by 34 %, which raised SCFAs production by 89.69 % (1269.65 mg COD /L). The balanced ratio of hydrolysis and fermentation communities suggested that the small molecular organics generated by the hydrolysis community could be sufficiently utilized by fermentation communities. The metabolism of amino acids and glucose was facilitated, and the activities of key enzymes were enhanced. These results clarified the effect of asynchronous enzyme cocktail pretreatment against HA inhibition and contributed to SCFAs production, which offered fresh perspectives on carbon recovery.

Proton Pump Inhibitors and Oral-Gut Microbiota: From Mechanism to Clinical Significance.

Proton pump inhibitors (PPIs) are some of the most commonly prescribed drugs worldwide, but there are increasing concerns about digestive complications linked to PPIs. Next-generation sequencing studies have suggested that PPIs can significantly affect the composition of the gut microbiota, which in turn may substantially contribute to the development of these complications. Recently, emerging evidence has suggested that the translocation of oral microbes into the gut may be the primary mechanism underlying the alterations in the gut microbiota induced by PPIs in the presence of gastric acid suppression and impaired oral-gut barrier function. Moreover, the significance of oral-gut microbial translocation in health and disease conditions has gained increasing recognition. Consequently, it is imperative to enhance our understanding of the functions of the oral-gut microbiota axis in digestive disorders associated with PPI therapies. This review aims to summarize current research findings and further elucidate the contribution of the oral-gut microbiota to the pathogenesis of PPI-related digestive diseases. We aim to provide a theoretical foundation for future therapeutic and preventive strategies targeting PPI-related digestive complications through modulation of the oral-gut microbiota.

12369 Clinical Experience With Inclisiran At An Academic Center

Abstract Disclosure: L. Chavez Marin: None. M. Gonzalez: None. M.F. Linton: None. B.G. Carranza Leon: None. Background: Inclisiran, a small interfering RNA (siRNA) molecule designed to inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), is the only siRNA approved for management of elevated low-density lipoprotein cholesterol (LDL-C) in both primary (for patients with familial hypercholesterolemia) and secondary prevention of cardiovascular disease. In clinical trials, Inclisiran has been shown to reduce LDL-C by more than 50% in populations at high cardiovascular risk. However, real world data about its tolerability and efficacy is still limited. Methods: We conducted an electronic medical record search to identify subjects who were prescribed Inclisiran at a lipid clinic within Vanderbilt University Medical Center (Nashville, USA). Subjects were included if they received at least one dose of Inclisiran and had pre- and post- LDL-C levels. Subjects taking other LDL-C lowering medications like statins, ezetimibe, bempedoic acid, and PCSK-9 inhibitors were included. Pre- and post- LDL-C averages were calculated and analyzed with 95% confidence intervals. The reasons for medication discontinuation were also examined. Results: Out of 69 subjects identified, only 19 met criteria for inclusion, while 32 never received a dose due to cost burden and insurance denial. The other 18 subjects were not included due to inadequate lab results at the time of data collection. In subjects who received at least one dose of Inclisiran, average pre-LDL-C was 142 mg/dL [CI: 34.7] while post-LDL-C was 77 mg/dL [CI: 24.0], notable for a 46% decrease in LDL-C levels. These subjects were also receiving another lipid lowering agent, like a statin, or had previously used a monoclonal antibody-PCSK-9 inhibitor. Those without prior use of PCSK-9 inhibitors were also analyzed. Average pre-LDL-C was 109.5 mg/dL [CI: 15.8] while post-LDL-C was 39.8 mg/dL [CI: 17.2], which revealed a 64% decrease in LDL-C levels. The main reason for discontinuation of Inclisiran was insurance denial followed by individual preference. Only one subject discontinued Inclisiran due to experiencing a generalized rash. Conclusions: Inclisiran is an effective and overall well-tolerated medication indicated for the management of elevated LDL cholesterol. Our study revealed that for individuals with above goal LDL-C, despite maximum tolerated therapy with a statin, additional LDL-C lowering benefits can be seen with Inclisiran use. However, insurance approval and cost burden seem to be the main barriers for access. Presentation: 6/3/2024

Global Transcriptomic Analysis of Topical Sodium Alginate Protection against Peptic Damage in an In Vitro Model of Treatment-Resistant Gastroesophageal Reflux Disease.

Breakthrough symptoms are thought to occur in roughly half of all gastroesophageal reflux disease (GERD) patients despite maximal acid suppression (proton pump inhibitor, PPI) therapy. Topical alginates have recently been shown to enhance mucosal defense against acid-pepsin insult during GERD. We aimed to examine potential alginate protection of transcriptomic changes in a cell culture model of PPI-recalcitrant GERD. Immortalized normal-derived human esophageal epithelial cells underwent pretreatment with commercial alginate-based anti-reflux medications (Gaviscon Advance or Gaviscon Double Action), a matched-viscosity placebo control, or pH 7.4 buffer (sham) alone for 1 min, followed by exposure to pH 6.0 + pepsin or buffer alone for 3 min. RNA sequencing was conducted, and Ingenuity Pathway Analysis was performed with a false discovery rate of ≤0.01 and absolute fold-change of ≥1.3. Pepsin-acid exposure disrupted gene expressions associated with epithelial barrier function, chromatin structure, carcinogenesis, and inflammation. Alginate formulations demonstrated protection by mitigating these changes and promoting extracellular matrix repair, downregulating proto-oncogenes, and enhancing tumor suppressor expression. These data suggest molecular mechanisms by which alginates provide topical protection against injury during weakly acidic reflux and support a potential role for alginates in the prevention of GERD-related carcinogenesis.

Game changer for anaerobic fermentation of paper mulberry: Sucrose-loaded biochar enhancing microbial communities and lactic acid fermentation

This study investigated biochar effects, either alone or combined with sucrose, on fermentation quality, microbial communities, and in vitro rumen digestion of anaerobic fermented paper mulberry. The biochar alkaline functional groups bind to lactic acid, reducing acid inhibition and promoting Lactiplantibacillus proliferation. Owing to the low sugar content of paper mulberry, lactic acid bacteria in the biochar group primarily underwent heterofermentation, resulting in the lowest lactic and highest acetic acid contents. Treated with sucrose-loaded biochar, the increased substrate supported homofermentation, leading to the highest lactic and lowest acetic acid contents, with a 15.0 % increase in lactic acid and a 22.2 % decrease in ammoniacal nitrogen compared with the control after 75 days. In vitro rumen tests showed that the biochar-sucrose group had the highest dry matter degradation rate (45.9 %) and a 24.2 % reduction in methane emissions. Concludingly, sucrose-loaded biochar is recommended as effective for lactic acid production under anaerobic conditions.

Corrosion inhibitor from nature: Fundamentals of tannic acid inhibition for AA2024 alloy

This study addresses the fundamentals of corrosion inhibition of AA2024 alloy by tannic acid (TA), a Cr-free and eco-friendly natural product. To this end, the AA2024 alloy was immersed in NaCl solution (50 mM) with different TA concentrations (0.1–10 mM) for 7 days. Surface (SEM, Raman, and SKPFM) and electrochemical analyses (EIS, PDP, and SVET) revealed mixed inhibition after 1 day of immersion in TA solution. Long-term immersion tests in TA solutions produced a tannate-rich oxide film on the surface. The films with low tannate content (formed in 0.1 and 1 mM TA) showed the highest stability and corrosion resistance.

Dehydroepiandrosterone suppresses human colorectal cancer progression through ER stress-mediated autophagy and apoptosis in a p53-independent manner.

Colorectal cancer (CRC) is one of the primary contributors to cancer-related fatalities, with up to 80% of advanced CRC cases exhibiting mutations in the p53 gene. Unfortunately, the development of new compounds targeting mutant p53 is quite limited. The anticancer effects of Dehydroepiandrosterone (DHEA) on various cancers have been reported. However, the suppressive effect of DHEA on CRC cells harboring wild-type or mutant p53 gene remains controversial. This study emphasized revealing the suppressive mechanism and the effect of DHEA on CRC cell tumorigenesis in the presence of wild-type or mutant p53 gene. We demonstrate that DHEA causes CRC cell death and cell cycle arrest in a dose and time-dependent manner. Notably, DHEA exhibits similar inhibitory effects on CRC cells regardless of the p53 gene status. Further study reveals that DHEA induces endoplasmic reticulum (ER) stress and triggers PERK/eIF2/ATF4/CHOP UPR signaling pathway to activate autophagy followed by apoptosis, which was confirmed by suppression of 4-phenylbutyric acid (an ER stress inhibitor) or knockdown either ATF4 or CHOP. DHEA-induced apoptosis was attenuated by silencing ATG5 gene in either p53+/+ or p53-/- CRC cells, indicating autophagy regulation of apoptosis. Furthermore, DHEA treatment accompanied by bafilomycin A1 (a blocker of autophagosome degradation) leads to the accumulation of ATF4, CHOP, DR5, and p21 levels in CRC cells, implying that the degradative autophagy machinery regulates these four molecules. Consistently, DHEA demonstrates its inhibitory effect by suppressing CRC tumor formation in vivo. Altogether, we provide compelling evidence that DHEA is a potential therapeutic candidate for CRC patient treatment regardless of the p53 status through ER stress-PERK-autophagy-apoptosis axis.

Impact of different gastric acid suppressants on chronic unpredictable mild stress-induced cognitive impairment in rats: A possible involvement of gut dysbiosis

Recently, clinical evidence indicates that gastric acid suppressants are associated with an increased risk of the development of cognitive impairment and dementia, especially in elderly patients and those with mild cognitive impairment. Therefore, the aim of this research was to explore the impact of different gastric acid suppressants use, famotidine (Famo), esomeprazole (Esome) and vonoprazan (Vono) in the absence or the presence of chronic unpredictable mild stress (CUMS) on several memory tasks with examination of the role of gut dysbiosis. In the present study, rats received famotidine (3.7 mg/kg/day, p.o.) or esomeprazole (3.7 mg/kg/day, p.o.) or vonoprazan (1.85 mg/kg/day, p.o.) for 7 weeks with or without exposure to CUMS. Remarkably, CUMS with different acid suppressants caused a significant decrease in all memory tasks in late CUMS in the current investigation. CUMS with acid suppressants also revealed a marked alteration in the fecal Firmicutes/Bacteroidetes ratio compared to CUMS alone. This gut microbiome alteration was associated with an alteration in gut membrane integrity, as revealed by colonic histopathology and an elevation of systemic inflammatory markers. Besides, upregulation of hippocampal amyloid β and p-tau proteins and modification of brain histopathology were noticed. Our findings support the detrimental effect of gastric acid suppressants, especially proton pump inhibitors, on cognitive impairment in the presence of stress, with the possible involvement of gut dysbiosis.