Lactobacillus paracasei AH2 isolated from Chinese sourdough alleviated gluten-induced food allergy through modulating gut microbiota and promoting short-chain fatty acid accumulation in a BALB/c mouse model.

BACKGROUND: A large number of people worldwide suffer from gluten-induced food allergy. As investigated in our previous research, Lactobacillus paracasei AH2 isolated from traditionally homemade sourdough in Anhui province of China showed the potential to reduce the immune reactivity of wheat protein by in vitro evaluation. However, whether L. paracasei AH2 has a role in alleviating wheat allergy in an in vivo model and its underlying mechanisms have not been elucidated. RESULTS: In this study, the alleviative effects of L. paracasei AH2 on gluten-induced allergic response were evaluated. Compared with a gluten-allergic mouse, L. paracasei AH2 suppressed anaphylaxis symptoms, gluten-specific immunoglobulin E, histamine and interleukin-4. Moreover, L. paracasei AH2 attenuated splenomegaly and induced Th1 or Treg cell differentiation to modulate the Th1/Th2 immune balance toward Th1 polarization. Short-chain fatty acid (SCFA) levels were enhanced after L. paracasei AH2 supplementation, contributing to allergy relief as well as reducing the pH of colonic contents. The α and ß diversities of the gut microbiota were modulated by L. paracasei AH2 with increased relative abundance of Lacticaseibacillus and SCFA producers (Faecalibaculum, Alloprevotella and Bacteroides genera), as well as decreased unfavorable Lachnospiraceae_NK4A136_group and Alistipes. Additionally, L. paracasei AH2 protected the intestinal barrier function by upregulating tight junctions and improved the antioxidant activities in serum. CONCLUSION: Our findings indicate that L. paracasei AH2 could act as a potential probiotic for relieving wheat allergy by modulating the gut microbiota and elevating SCFA levels. © 2023 Society of Chemical Industry.

Increasing the pressure during high pressure homogenization regulates the starch digestion of the resulting pea starch-gallic acid complexes.

The pea starch-gallic acid (PS-GA) complexes were prepared using high pressure homogenization (HPH), then the effect and underlying mechanism of pressure on multi-scale structure and digestibility of complexes were investigated. Results showed that HPH promoted the formation of PS-GA complexes, reaching the maximum complex index of 7.74 % at the pressure of 90 MPa, and the main driving force were hydrophobic interactions and hydrogen bonding. The interaction between PS and GA facilitated the formation of surface reticular structures to encapsulate gallic acid molecules, further entangled into bigger size aggregates. The enhancement of rearrangement and aggregation of starch chains during HPH developed a dense hierarchical structure of PS-GA complexes, including short-range ordered structure, V-type crystal structure, lamellar and fractal structure, thus increasing gelatinization temperature. The digestibility of PS-GA complexes substantially changed in reducing rapidly digestible starch content from 29.67 % to 17.07 %, increasing slowly digestible starch from 53.69 % to 56.25 % and resistant starch from 16.63 % to 26.67 %, respectively. Moreover, the resulting complexes exhibited slower digestion rates compared with native PS. Furthermore, the regulating mechanism of pressure during HPH on starch digestibility was the formation of ordered multi-scale structure and inhibition of GA on digestive enzymes.

The high dose of inulin exacerbated food allergy through the excess accumulation of short-chain fatty acids in a BABL/c mouse model.

Inulin dietary supplement is conventionally beneficial to gut health and can potentially prevent food allergy (FA). This study aimed to determine how dietary inulin interventions at different doses affect the OVA-induced FA in a BALB/c mouse model. Although the middle dose of inulin (50 mg per mouse) showed the best therapeutic effect on FA, high-inulin supplementation (80 mg per mouse) provoked severe allergic and intestinal inflammatory responses, which were characterized by elevated serum allergic inflammation-related factor levels, dysfunctional gut barrier, unbalanced luminal pH value, decrease in intestinal antioxidant capacity, and disordered gut microecology. Moreover, profiling of SCFAs indicated that the high-inulin-induced excess accumulation of SCFAs in the colon was responsible for the gut immune disorders. Spearman correlation analysis unraveled that the featured bacterial taxa in the high-inulin-treated mice were Ruminococcaceae and Bifidobacterium, of which the relative abundance was negatively correlated with expression of tight junction proteins and improvement of T cell homeostasis, and positively correlated with levels of allergic inflammation-related indexes. Our work suggested that high-inulin dietary supplementation can be detrimental to allergic individuals and highlighted the importance for personalized use of inulin-type dietary supplements to safely improve human health.

Inactivation of EGLN3 hydroxylase facilitates Erk3 degradation via autophagy and impedes lung cancer growth.

EGLN3 is critically important for growth of various cancers including lung cancer. However, virtually nothing is known about the role and mechanism for EGLN3 hydroxylase activity in cancers. EGLN3 catalyzes the hydroxylation of extracellular signal-regulated kinase 3 (Erk3), a potent driver of cancers. The role and mechanism for EGLN3-induced stabilization of Erk3 remain to be defined. Here, we show that Erk3 interacts with heat shock cognate protein of 70 kDa (HSC70) and lysosome-associated membrane protein type 2 A (LAMP2A), two core components of chaperone-mediated autophagy (CMA). As a consequence, Erk3 is degraded by the CMA-lysosome pathway. EGLN3-catalyzed hydroxylation antagonizes CMA-dependent destruction of Erk3. Mechanistically, hydroxylation blunts the interaction of Erk3 with LAMP2A, thereby blocking lysosomal decay of Erk3. EGLN3 inactivation inhibits macrophage migration, efferocytosis, and M2 polarization. Studies using EGLN3 catalytically inactive knock-in mice indicate that inactivation of EGLN3 hydroxylase in host cells ameliorates LLC cancer growth through reprogramming the tumor microenvironment (TME). Adoptive transfer of macrophages with inactivated EGLN3 restrains tumor growth by mounting anti-tumor immunity and restricting angiogenesis. Administration of EGLN3 hydroxylase pharmacologic inhibitor to mice bearing LLC carcinoma impedes cancer growth by targeting the TME. LLC cells harboring inactivated EGLN3 exhibit reduced tumor burden via mitigating immunosuppressive milieu and inducing cancer senescence. This study provides novel insights into the role of CMA in regulating Erk3 stability and the mechanism behind EGLN3-enhanced stability of Erk3. This work demonstrates that inactivation of EGLN3 in malignant and stromal cells suppresses tumor by orchestrating reciprocal interplays between cancer cells and the TME. This work sheds new light on the role and mechanism for EGLN3 catalytic activity in regulating cancer growth. Manipulating EGLN3 activity holds promise for cancer treatment.

Novel Role for Tranilast in Regulating NLRP3 Ubiquitination, Vascular Inflammation, and Atherosclerosis.

Background Aberrant activation of the NLRP3 (nucleotide-binding oligomerization domain, leucine-rich repeat-containing receptor family pyrin domain-containing 3) inflammasome is thought to play a causative role in atherosclerosis. NLRP3 is kept in an inactive ubiquitinated state to avoid unwanted NLRP3 inflammasome activation. This study aimed to test the hypothesis that pharmacologic manipulating of NLRP3 ubiquitination blunts the assembly and activation of the NLRP3 inflammasome and protects against vascular inflammation and atherosclerosis. Since genetic studies yielded mixed results about the role for this inflammasome in atherosclerosis in low-density lipoprotein receptor- or apolipoprotein E-deficient mice, this study attempted to clarify the discrepancy with the pharmacologic approach using both models. Methods and Results We provided the first evidence demonstrating that tranilast facilitates NLRP3 ubiquitination. We showed that tranilast restricted NLRP3 oligomerization and inhibited NLRP3 inflammasome assembly. Tranilast markedly suppressed NLRP3 inflammasome activation in low-density lipoprotein receptor- and apolipoprotein E-deficient macrophages. Through reconstitution of the NLRP3 inflammasome in human embryonic kidney 293T cells, we found that tranilast directly limited NLRP3 inflammasome activation. By adopting different regimens for tranilast treatment of low-density lipoprotein receptor- and apolipoprotein E-deficient mice, we demonstrated that tranilast blunted the initiation and progression of atherosclerosis. Mice receiving tranilast displayed a significant reduction in atherosclerotic lesion size, concomitant with a pronounced decline in macrophage content and expression of inflammatory molecules in the plaques compared with the control group. Moreover, tranilast treatment of mice substantially hindered the expression and activation of the NLRP3 inflammasome in the atherosclerotic lesions. Conclusions Tranilast potently enhances NLRP3 ubiquitination, blunts the assembly and activation of the NLRP3 inflammasome, and ameliorates vascular inflammation and atherosclerosis in both low-density lipoprotein receptor- and apolipoprotein E-deficient mice.

Asymmetric Thermoelectrochemical Cell for Harvesting Low-grade Heat under Isothermal Operation.

Low-grade heat is abundantly available in the environment as waste heat. The efficient conversion of low-grade heat into electricity is very difficult. We developed an asymmetric thermoelectrochemical cell (aTEC) for heat-to-electricity conversion under isothermal operation in the charging and discharging processes without exploiting the thermal gradient or the thermal cycle. The aTEC is composed of a graphene oxide (GO) cathode, a polyaniline (PANI) anode, and 1M KCl as the electrolyte. The cell generates a voltage due to the pseudocapacitive reaction of GO when heating from room temperature (RT) to a high temperature (TH, ~40-90 °C), and then current is successively produced by oxidizing PANI when an external electrical load is connected. The aTEC demonstrates a remarkable temperature coefficient of 4.1 mV/K and a high heat-to-electricity conversion efficiency of 3.32%, working at a TH = 70 °C with a Carnot efficiency of 25.3%, unveiling a new promising thermoelectrochemical technology for low-grade heat recovery.

Direct thermal charging cell for converting low-grade heat to electricity.

Efficient low-grade heat recovery can help to reduce greenhouse gas emission as over 70% of primary energy input is wasted as heat, but current technologies to fulfill the heat-to-electricity conversion are still far from optimum. Here we report a direct thermal charging cell, using asymmetric electrodes of a graphene oxide/platinum nanoparticles cathode and a polyaniline anode in Fe2+/Fe3+ redox electrolyte via isothermal heating operation. When heated, the cell generates voltage via a temperature-induced pseudocapacitive effect of graphene oxide and a thermogalvanic effect of Fe2+/Fe3+, and then discharges continuously by oxidizing polyaniline and reducing Fe3+ under isothermal heating till Fe3+ depletion. The cell can be self-regenerated when cooled down. Direct thermal charging cells attain a temperature coefficient of 5.0 mV K-1 and heat-to-electricity conversion efficiency of 2.8% at 70 °C (21.4% of Carnot efficiency) and 3.52% at 90 °C (19.7% of Carnot efficiency), outperforming other thermoelectrochemical and thermoelectric systems.

Research on electrocardiogram baseline wandering correction based on wavelet transform, QRS barycenter fitting, and regional method.

Baseline wandering in electrocardiogram (ECG) is one of the biggest interferences in visualization and computerized detection of waveforms (especially ST-segment) based on threshold decision. A new method based on wavelet transform, QRS barycenter fitting and regional method was proposed in this paper. Firstly, wavelet transform as a coarse correction was used to remove the baseline wandering, whose frequency bands were non-overlapping with that of ST-segment. Secondly, QRS barycenter fitting was applied as a detailed correction. The third, the regional method was used to transfer baseline to zero. Finally, the method in this paper was proved to perform better than filtering and function fitting methods in baseline wandering correction after the long-term ST database (LTST) verification. In addition, the proposed method is simple and easy to carry out, and in current use.