Short-term outcomes of three- and two-field lymphadenectomy with minimally invasive esophagectomy for esophageal cancer: a propensity score-matching analysis.

Background: Whether patients can benefit from three-field lymphadenectomy (3-FL) in minimally invasive esophagectomy (MIE) remains unclear. This study retrospectively compared short-term outcomes between 3-FL and two-field lymphadenectomy (2-FL) in MIE for patients with esophageal cancer (EC) and aimed to evaluate the clinical significance of 3-FL. Methods: There were 284 patients enrolled in the study (124 patients with 3-FL and 160 patients with 2-FL). The cases were matched based on their propensity scores using a matching ratio of 1:1, the nearest neighbor matching protocol, and a caliper of 0.02. Patients were propensity-score matched for sex, cancer location, Age-adjusted Charlson Comorbidity Index (ACCI), and neoadjuvant treatment. The short-term outcomes were postoperative complications, operation characteristics, pathology results and postoperative hospital stay. Results: There were no significant differences in intraoperative hemorrhage, postoperative hospital stay, or postoperative complications between the 2-FL and 3-FL groups. The operation time of the two groups was significantly different (227.1±46.2 vs. 248.5±45.9 min, P=0.001); the operation time of the 3-FL group was about 20 minutes longer than that of the 2-FL group. The number of lymphatic nodes (LNs) obtained in the 3-FL group was significantly higher than that in the 2-FL group (31.3±12.9 vs. 54.6±18.0, P<0.001). Pathological N stage was also significantly different (P=0.002); the 3-FL group was more advanced than the 2-FL group. Conclusions: Compared to 2-FL MIE, 3-FL MIE does not increase postoperative complications, can obtain more LNs, and improves the accuracy of tumor LN staging.

Tumor Cell Stemness and Stromal Cell Features Contribute to Oral Cancer Outcome Disparity in Black Americans.

Black Americans (BAs) with head and neck cancer (HNC) have worse survival outcomes compared to the White patients. While HNC disparities in patient outcomes for BAs have been well recognized, the specific drivers of the inferior outcomes remain poorly understood. Here, we investigated the biologic features of patient tumor specimens obtained during the surgical treatment of oral cancers and performed a follow-up study of the patients' post-surgery recurrences and metastases with the aim to explore whether tumor biologic features could be associated with the poorer outcomes among BA patients compared with White American (WA) patients. We examined the tumor stemness traits and stromal properties as well as the post-surgery recurrence and metastasis of oral cancers among BA and WA patients. It was found that high levels of tumor self-renewal, invasion, tumorigenesis, metastasis, and tumor-promoting stromal characteristics were linked to post-surgery recurrence and metastasis. There were more BA than WA patients demonstrating high stemness traits and strong tumor-promoting stromal features in association with post-surgery tumor recurrences and metastases, although the investigated cases displayed clinically comparable TNM stages and histological grades. These findings demonstrated that the differences in tumor stemness and stromal property among cancers with comparable clinical diagnoses contribute to the outcome disparity in HNCs. More research is needed to understand the genetic and molecular basis of the biologic characteristics underlying the inferior outcomes among BA patients, so that targeting strategies can be developed to reduce HNC disparity.

ISMI-VAE: A deep learning model for classifying disease cells using gene expression and SNV data.

Various studies have linked several diseases, including cancer and COVID-19, to single nucleotide variations (SNV). Although single-cell RNA sequencing (scRNA-seq) technology can provide SNV and gene expression data, few studies have integrated and analyzed these multimodal data. To address this issue, we introduce Interpretable Single-cell Multimodal Data Integration Based on Variational Autoencoder (ISMI-VAE). ISMI-VAE leverages latent variable models that utilize the characteristics of SNV and gene expression data to overcome high noise levels and uses deep learning techniques to integrate multimodal information, map them to a low-dimensional space, and classify disease cells. Moreover, ISMI-VAE introduces an attention mechanism to reflect feature importance and analyze genetic features that could potentially cause disease. Experimental results on three cancer data sets and one COVID-19 data set demonstrate that ISMI-VAE surpasses the baseline method in terms of both effectiveness and interpretability and can effectively identify disease-causing gene features.

Inhibition of the RLR signaling pathway by SARS-CoV-2 ORF7b is mediated by MAVS and abrogated by ORF7b-homologous interfering peptide.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and characterized by dysregulated immune response. Studies have shown that the SARS-CoV-2 accessory protein ORF7b induces host cell apoptosis through the tumor necrosis factor alpha (TNF-α) pathway and blocks the production of interferon beta (IFN-ß). The underlying mechanism remains to be investigated. In this study, we found that ORF7b facilitated viral infection and production, and inhibited the RIG-I-like receptor (RLR) signaling pathway through selectively interacting with mitochondrial antiviral-signaling protein (MAVS). MAVS439-466 region and MAVS Lys461 were essential for the physical association between MAVS and ORF7b, and the inhibition of the RLR signaling pathway by ORF7b. MAVSK461/K63 ubiquitination was essential for the RLR signaling regulated by the MAVS-ORF7b complex. ORF7b interfered with the recruitment of tumor necrosis factor receptor-related factor 6 (TRAF6) and the activation of the RLR signaling pathway by MAVS. Furthermore, interfering peptides targeting the ORF7b complex reversed the ORF7b-suppressed MAVS-RLR signaling pathway. The most potent interfering peptide V disrupts the formation of ORF7b tetramers, reverses the levels of the ORF7b-inhibited physical association between MAVS and TRAF6, leading to the suppression of viral growth and infection. Overall, this study provides a mechanism for the suppression of innate immunity by SARS-CoV-2 infection and the mechanism-based approach via interfering peptides to potentially prevent SARS-CoV-2 infection.IMPORTANCEThe pandemic coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and continues to be a threat to public health. It is imperative to understand the biology of SARS-CoV-2 infection and find approaches to prevent SARS-CoV-2 infection and ameliorate COVID-19. Multiple SARS-CoV-2 proteins are known to function on the innate immune response, but the underlying mechanism remains unknown. This study shows that ORF7b inhibits the RIG-I-like receptor (RLR) signaling pathway through the physical association between ORF7b and mitochondrial antiviral-signaling protein (MAVS), impairing the K63-linked MAVS polyubiquitination and its recruitment of tumor necrosis factor receptor-related factor 6 (TRAF6) to MAVS. The most potent interfering peptide V targeting the ORF7b-MAVS complex may reverse the suppression of the MAVS-mediated RLR signaling pathway by ORF7b and prevent viral infection and production. This study may provide new insights into the pathogenic mechanism of SARS-CoV-2 and a strategy to develop new drugs to prevent SARS-CoV-2 infection.

Warm Acupuncture Reduces Pain and Inflammation in Rats with Lumbar Disc Herniation Induced by Autologous Nucleus Pulposus Transplantation via Regulating p38MAPK/NF-κB Pathway.

Background: : Warm acupuncture (WA) has analgesic and anti-inflammatory effects. However, the underlying mechanism of these effects remain unclear. Objectives: : To explore the analgesic and anti-inflammatory effects of WA and the potential underlying mechanism in male Sprague-Dawley rats with non-compressive lumbar disk herniation (LDH) caused by autologous nucleus pulposus (NP) transplantation. Methods: : We used low-frequency (2 Hz) electrical stimulation and WA (40℃) to treat GB30 and BL54 acupoints in rats for 30 mins per day. We monitored the paw withdrawal threshold of rats during the experiment and measured serum cytokine levels using commercial kits. Dorsal root ganglion (DRG) tissue pathology was analyzed via H&E staining. We used qRT-PCR to measure the mRNA expression levels of IL-1ß, IL-6, and TNF-α genes in DRG. Western blot was used to analyze the expression levels of IL-1ß, IL-6, TNFα, P-p38MAPK, p38MAPK, P-IκBα, IκB α, and NF-κB p65 proteins. Results: : WA treatment significantly increased the pain threshold of rats, reduced serum IL-6, PEG2, NO, SP, NP-Y, and MMP-3 levels, and effected histopathological improvements in the DRG in rats. Moreover, WA treatment significantly downregulated the expression levels of inflammation-associated genes (Il-1ß, Il-6, and Tnf-α) and proteins (IL-1ß, IL-6, TNF-α, P-p38MAPK, P-IκBα, and NF-κB p65) in the DRG of non-compressive LDH rats. Conclusion: : WA can alleviate pain and inhibit inflammatory response in rats with non-compressive LDH caused by autologous NP transplantation, and these effects are likely associated with the inhibition of the p38MAPK/NF-κB pathway.

Construction and screening of spin-crossover-sponge materials based on iron(II)-triazole coordination polymers.

Iron(II)-triazole coordination polymers have attracted considerable interest for their synthetic versatility, which allows tuning their spin-crossover (SCO) properties. Embedding SCO solid particles in sponge matrices is a simple, powerful, and generic approach to construct processable SCO materials. Here, we have studied a series of magnetic frameworks based on partial ligand substitution by using different chemical mixtures of two organic ligands, yielding four isostructural coordination polymers. The integration of the hygroscopic SCO material has endowed the composite sponge with the ability to capture moisture under ambient conditions. In particular, not only does a spin-crossover transition during absorption occur, but also a color variation has been achieved by varying humidity. The consequences of cooperativity and the exposed surface of the composite sponge on the spin transition were evaluated and the most promising materials among them were screened. This work provides guiding significance for the fabrication and practical application of spin-crossover-sponge materials.

Immune regulation and inflammation inhibition of Arctium lappa L. polysaccharides by TLR4/NF-κB signaling pathway in cells.

Arctium lappa L. polysaccharides (ALP) are important active ingredients of burdocks with various bioactivities. In the present study, a crude polysaccharide was extracted from A. lappa L. roots and purified using DEAE-52 and Sephacryl™ S-400 columns to reach 99 % purity. This neutral polysaccharide contained fructose, glucose, galactose and arabinose in a ratio of 0.675:0.265:0.023:0.016 and had a Mw of 4256 Da. The immunomodulatory activity and intestinal inflammation inhibitory effects of ALP were investigated in in vitro models, including lipopolysaccharide-induced macrophage RAW264.7 and interleukin (IL)-1ß-induced colon Caco-2 cells. The results revealed that ALP possessed both antioxidant and anti-inflammatory effects by decreasing nuclear factor-E2-related factor 2 mRNA expression and reactive oxygen species. Furthermore, ALP was found to have inhibitory effects on pro-inflammatory cytokines, including IL-8, IL-6, IL-1ß, and tumor necrosis factor-α, as well as inflammatory cytokines, such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and monocyte chemoattractant protein-1 by down-regulating the Toll-like receptor 4 (TLR4)/NF-κB (nuclear factor-kappa B signaling) pathway. It indicated that A. lappa L. was an ideal source of bioactive polysaccharides having potential to be developed as functional foods or nutraceuticals to improve immune system and prevent/treat intestinal inflammation.

Arctium lappa L. roots inhibit the intestinal inflammation of dietary obese rats through TLR4/NF-κB pathway.

Long-term consumption of Arctium lappa L. roots can lead to weight loss. To explore the relationship between anti-obesity and anti-inflammation, the effects and mechanism of A. lappa L. root powder (ARP) on intestinal inflammation in obese rats were investigated. Dietary obese rats were successfully established by feeding a high-fat and high-sugar diet. The control group (n = 6) consumed a normal diet. The intestines were compared among the groups (each n = 6) with and without the administration of ARP (intragastric 7.5 g/kg·bw/d). Real-time quantitative reverse transcription-polymerase chain reaction and western blotting analysis revealed that ARP effectively inhibited the expression of pro-inflammatory and inflammatory cytokines in the colons of obese rats. These cytokines included interleukin (IL)-1ß, IL-8, IL-6, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. The inhibition rates for all these cytokines exceeded 88 %. Moreover, ARP demonstrated the ability to down-regulate key genes involved in Toll-like receptor 4 (TLR4) complexes, namely Tlr4, myeloid differentiation protein-2 (Md2), and myeloid differentiation factor 88 (Myd88), along with downstream signaling molecules such as tumor necrosis factor receptor associated factor 6 (TRAF6) and nuclear factor-κB (NF-κB), with inhibition rates over 81 %. Additionally, ARP was observed to inhibit protein levels of TLR4, NF-κB, IL-1ß, and TNF-α in the colons of obese rats, with inhibition rates of 65.6 ± 10.9 %, 84.4 ± 19.9 %, 80.8 ± 14.4 %, and 68.4 ± 17.5 %, respectively. This study confirmed the effectiveness of ARP in inhibiting intestinal inflammation through the blockade of the TLR4/NF-κB signaling pathway. It also suggested that ARP holds potential in improving intestinal health in the context of obesity, implying its possible application in the prevention and treatment of obesity and related metabolic diseases.

Effects of epigallocatechin-3-gallate on oxidative stress, inflammation, and bone loss in a rat periodontitis model.

Background/purpose: Epigallocatechin-3-gallate (EGCG) is playing an increasingly important role in the treatment of oral diseases. However, its mechanisms remain to be clarified. This study aimed to investigate the effect of EGCG on oxidative and inflammatory stress and bone loss in experimental periodontitis. Materials and methods: Periodontitis was induced in rats, followed by gavage using different concentrations of EGCG for 5 weeks. The levels of interleukin-1ß (IL-1ß), interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) in rats were measured. The degree of alveolar bone loss and the number of inflammatory cells were detected. The integrated optical density of nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase-1 (HO-1), NLR pyrin domain-containing 3 (NLRP3) and nuclear factor-kappaB p65 (NF-κB p65) was measured. Results: EGCG (200 mg/kg) significantly reduced alveolar bone loss in the ligated maxillary molars and the number of inflammatory cells in the EGCG-200 group compared with the periodontitis, EGCG-100 and EGCG-400 groups. 200 mg/kg was the optimal dose of EGCG and was used in subsequent experiments. The expression levels of IL-1ß, IL-18, TNF-α and MDA were significantly lower and the expression level of SOD was significantly higher in the EGCG-200 group compared with the periodontitis group. The expression of NLRP3 and NF-κB p65 was significantly decreased, while the expression of Nrf2 and HO-1 was significantly increased in the EGCG-200 group compared with the periodontitis group. Conclusion: These results suggest that EGCG inhibits oxidative stress and inflammatory responses in the periodontitis model by modulating the Nrf2/HO-1/NLRP3/NF-κB p65 signaling pathway, thereby decreasing alveolar bone loss.

USP14 Positively Modulates Head and Neck Squamous Carcinoma Tumorigenesis and Potentiates Heat Shock Pathway through HSF1 Stabilization.

The ubiquitin-proteasome system is a pivotal intracellular proteolysis process in posttranslational modification. It regulates multiple cellular processes. Deubiquitinating enzymes (DUBs) are a stabilizer in proteins associated with tumor growth and metastasis. However, the link between DUBs and HNSCC remains incompletely understood. In this study, therefore, we identified USP14 as a tumor proliferation enhancer and a substantially hyperactive deubiquitinase in HNSCC samples, implying a poor prognosis prediction. Silencing USP14 in vitro conspicuously inhibited HNSCC cell proliferation and migration. Consistently, defective USP14 in vivo significantly diminished HNSCC tumor growth and lung metastasis compared to the control group. Luciferase assays indicated that HSF1 was downstream from USP14, and an evaluation of the cellular effects of HSF1 overexpression in USP14-dificient mice tumors showed that elevated HSF1 reversed HNSCC growth and metastasis predominantly through the HSF1-HSP pathway. Mechanistically, USP14 encouraged HSF1 expression by deubiquitinating and stabilizing HSF1, which subsequently orchestrated transcriptional activation in HSP60, HSP70, and HSP90, ultimately leading to HNSCC progression and metastasis. Collectively, we uncovered that hyperactive USP14 contributed to HNSCC tumor growth and lung metastasis by reinforcing HSF1-depedent HSP activation, and our findings provided the insight that targeting USP14 could be a promising prognostic and therapeutic strategy for HSNCC.

Preparation of low molecular weight polysaccharides from Tremella fuciformis by ultrasonic-assisted H2O2-Vc method: Structural characteristics, in vivo antioxidant activity and stress resistance.

Different methods were used to degrade Tremella fuciformis polysaccharides (TFP) and prepare low molecular weight polysaccharides of Tremella fuciformis (TFLP) to improve their bioavailability. It was found that the TFLP prepared by ultrasonic-assisted H2O2-Vc method showed the highest level of antioxidant activity and stress resistance in C. elegans. The structural characteristics, in vivo antioxidant and stress resistance of TFLP-1 were evaluated after isolation and purification of TFLP, it was found that TFLP-1 was an acid polysaccharide with a molecular weight of 75770 Da, which mainly composed of mannose. Meanwhile, it could regulate the antioxidant activity and stress resistance in C. elegans by upregulating the transcription of fat-5, fat-7, acs-2, glp-1, hsf-1, hsp-1, mtl-1, nhr-49, skn-1 and sod-3 mRNA. The improvement effects were closely related to the significant regulation of galactose metabolism, alpha linolenic acid metabolism, and pantothenate and CoA biosynthesis metabolic pathways. These results provided insights into the high value application of Tremella fuciformis in the food industry and the development of antioxidant related functional foods.

YWHAH activates the HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect the proliferation of gastric cancer cells.

Fos-related antigen 1 (Fra-1) is a nuclear transcription factor that regulates cell growth, differentiation, and apoptosis. It is involved in the proliferation, invasion, apoptosis and epithelial mesenchymal transformation of malignant tumor cells. Fra-1 is highly expressed in gastric cancer (GC), affects the cycle distribution and apoptosis of GC cells, and participates in GC occurrence and development. However, the detailed mechanism of Fra-1 in GC is unclear, such as the identification of Fra-1-interacting proteins and their role in GC pathogenesis. In this study, we identified tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH) as a Fra-1-interacting protein in GC cells using co-immunoprecipitation combined with liquid chromatography-tandem mass spectrometry. Experiments showed that YWHAH positively regulated Fra-1 mRNA and protein expression, and affected GC cell proliferation. Whole proteome analysis showed that Fra-1 affected the activity of the high mobility group AT-hook 1 (HMGA1)/phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway in GC cells. Western blotting and flow cytometry confirmed that YWHAH activated HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect GC cell proliferation. These results will help to discover new molecular targets for the early diagnosis, treatment, and prognosis prediction of GC.

Effects of glycolysis on the polarization and function of tumor­associated macrophages (Review).

Under conditions of oxygen sufficiency, tumor cells supply themselves with energy through glycolysis, which is one of the causes of their rapid proliferation, metastasis and acquisition of drug resistance. Tumor­associated macrophages (TAMs) are transformed from peripheral blood monocytes and are among the immune­related cells that constitute the tumor microenvironment (TME). Altered glycolysis levels in TAMs have an important impact on their polarization and function. The cytokines secreted by TAMs, and phagocytosis in different polarization states, affect tumorigenesis and development. Furthermore, changes in glycolysis activity of tumor cells and other immune­related cells in the TME also affect the polarization and function of TAMs. Studies on the relationship between glycolysis and TAMs have received increasing attention. The present study summarized the link between glycolysis of TAMs and their polarization and function, as well as the interaction between changes in glycolysis of tumor cells and other immune­associated cells in the TME and TAMs. The present review aimed to provide a comprehensive understanding of the effects of glycolysis on the polarization and function of TAMs.

Real-world dose escalation of biologics for moderate-to-severe psoriasis in the United States.

AIM: To compare real-world dose escalation of risankizumab with other US Food and Drug Administration (FDA)-approved biologic treatments for management of moderate-to-severe psoriasis (PsO) in the United States. METHODS: The Merative® MarketScan® Research Database was used to identify adults with ≥2 medical claims for PsO, ≥3 claims of the index biologic medication in the maintenance period, and ≥6 months continuous enrollment pre-induction and ≥6 months after initiation of the maintenance period. Dose escalation was defined as ≥2 dosing intervals where the average daily dose was ≥30% higher than the expected daily dose (per FDA-approved dosing). Comparisons between risankizumab and other cohorts were made using chi-square tests and logistic regression models. RESULTS: At the 30% threshold, the percentage of patients with dose escalation in the full maintenance period was significantly lower with risankizumab (2.0%) compared with other drug classes (tumor necrosis factor, interleukin (IL)-12/23, IL-17, or other IL-23 inhibitors: 17.6%, 10.0%, 18.3%, or 7.1%, respectively; p < 0.0001 for each) and individual biologics (adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab; 17.9%, 10.0%, 15.7%, 18.0%, and 7.2%, respectively; p < 0.0001). CONCLUSION: A significantly lower proportion of risankizumab-treated patients with PsO had dose escalations compared with patients treated with other biologics.

Integrative analysis of single-cell transcriptomics reveals age-associated immune landscape of glioblastoma.

Glioblastoma (GBM) is the most malignant tumor in center nervous system. Clinical statistics revealed that senior GBM patients had a worse overall survival (OS) comparing with that of patients in other ages, which is mainly related with tumor microenvironment including tumor-associated immune cells in particular. However, the immune heterogeneity and age-related prognosis in GBM are under studied. Here we developed a machine learning-based method to integrate public large-scale single-cell RNA sequencing (scRNA-seq) datasets to establish a comprehensive atlas of immune cells infiltrating in cross-age GBM. We found that the compositions of the immune cells are remarkably different across ages. Brain-resident microglia constitute the majority of glioblastoma-associated macrophages (GAMs) in patients, whereas dramatic elevation of extracranial monocyte-derived macrophages (MDMs) is observed in GAMs of senior patients, which contributes to the worse prognosis of aged patients. Further analysis suggests that the increased MDMs arisen from excessive recruitment and proliferation of peripheral monocytes not only lead to the T cell function inhibition in GBM, but also stimulate tumor cells proliferation via VEGFA secretion. In summary, our work provides new cues for the correlational relationship between the immune microenvironment of GBM and aging, which might be insightful for precise and effective therapeutic interventions for senior GBM patients.

Role and mechanism of CD90+ fibroblasts in inflammatory diseases and malignant tumors.

Fibroblasts are highly heterogeneous mesenchymal stromal cells, and different fibroblast subpopulations play different roles. A subpopulation of fibroblasts expressing CD90, a 25-37 kDa glycosylphosphatidylinositol anchored protein, plays a dominant role in the fibrotic and pro-inflammatory state. In this review, we focused on CD90+ fibroblasts, and their roles and possible mechanisms in disease processes. First, the main biological functions of CD90+ fibroblasts in inducing angiogenesis and maintaining tissue homeostasis are described. Second, the role and possible mechanism of CD90+ fibroblasts in inducing pulmonary fibrosis, inflammatory arthritis, inflammatory skin diseases, and scar formation are introduced, and we discuss how CD90+ cancer-associated fibroblasts might serve as promising cancer biomarkers. Finally, we propose future research directions related to CD90+ fibroblasts. This review will provide a theoretical basis for the diagnosis and treatment CD90+ fibroblast-related disease.

Design, synthesis and pharmacological evaluation of ß-carboline derivatives as potential antitumor agent via targeting autophagy.

A series of novel ß-carboline derivatives was designed, synthesized and evaluated as potential anticancer agents. Among them, compound 6g showed the most potent antiproliferative activity against the 786-0, HT-29 and 22RV1 cell lines with IC50 values of 2.71, 2.02, and 3.86 µM, respectively. The antitumor efficiency of compound 6gin vivo was also evaluated, and the results revealed that compound 6g significantly suppressed tumor development and reduced tumor weight in a mouse colorectal cancer homograft model. Further investigation on mechanisms of action demonstrated that compound 6g inhibited HCT116 cell growth by stimulating the ATG5/ATG7-dependent autophagic pathway. These molecules might be served as candidates for further development of colorectal cancer therapy agent.

Physiological mechanisms of TLR4 in glucolipid metabolism regulation: Potential use in metabolic syndrome prevention.

Over-nourishment or an unbalanced diet has been linked to an increase in the prevalence of metabolic syndrome. An imbalance in glucolipid metabolism is a major cause of metabolic syndrome, which has consequences for human health. Toll-like receptor 4 (TLR4), a member of the innate immune pattern recognition receptor family, is involved in inflammation-related disorders, autoimmune diseases, and tumors. Recent research has shown that TLR4 plays a key role in glucolipid metabolism, which is linked to insulin resistance, intestinal flora, and the development of chronic inflammation. TLR4 activation regulates glucolipid metabolism and contributes to the dynamic relationship between innate immunity and nutrition-related disorders. Further, TLR4 regulates glucolipid metabolism by controlling glycolysis and pyruvate oxidative decarboxylation, interfering with insulin signaling, regulating adipogenic gene expression levels, influencing preadipocyte differentiation and lipid accumulation, and altering the intestinal microbiota and permeability. TLR4 functions may provide new therapeutic applications for the prevention and treatment of metabolic syndrome. The purpose of this review is to enrich mechanistic research of diabetes, atherosclerosis, and other nutrition-related disorders by summarizing the role of TLR4 in the regulation of glucolipid metabolism as well as its physiological mechanisms.

Thermostable ficin from jelly fig (Ficus pumila var. awkeotsang) latex: purification, identification and characterization.

BACKGROUND: The achenes/seeds of endemic jelly fig (Ficus pumila var. awkeotsang) fruit have been applied to prepare a traditional beverage in Taiwan. Upon fruit harvest, jelly fig latex exuded from stalks was discarded. Protease activity was monitored in its latex. Proteases capable of hydrolyzing proteins have many application aspects based on diverse characteristics. Commercial plant proteases are frequently from latex. RESULTS: The latex protease of jelly fig, termed FaFicin, was purified to homogeneity with a molecular mass of ~32 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. According to liquid chromatographic-tandem mass spectrometric analyses, the expected protein band of protease was matched to ficin A, ficin B or chymopapain from common fig or papaya. Iodoacetamide, an inhibitor of cysteine protease, inhibited its protease activity completely. Hence FaFicin was identified as a papain-like cysteine protease (PLCP), exhibiting more than 80% and 70% activity as assayed at pH 5-8 and 40-70 °C, respectively. It maintained ~89% of initial activity after 120 min at 55 °C and pH 7. Moreover, FaFicin could degrade the myosin and actin of meat, and clot milk. CONCLUSION: The ficin FaFicin was obtained, purified and identified as a PLCP member from agricultural waste: jelly fig latex. It possessed activity under a wide range of pH values and temperature, and exhibited excellent thermostability. Based on its initial evaluation as a meat tenderizer and milk clotting reagent, the application of FaFicin was possible, which may extend utilization of jelly fig. © 2022 Society of Chemical Industry.