The role of interleukin 36γ in the epithelial-mesenchymal transition process of chronic rhinosinusitis: A pilot study.

PURPOSE: Epithelial-mesenchymal transition (EMT) is an important characteristic in the remodelling of chronic rhinosinusitis with nasal polyps (CRSwNP). IL-36γ and fibroblast activation protein (FAP) may exacerbate remodelling in CRS. Here, we aimed to determine whether IL-36γ and FAP expression are associated with EMT and may be a predictor for CRSwNP prognosis. METHODS: Fifty-two non-Eos CRSwNP patients and 12 control patients were obtained and were followed up for more than 1 year after surgery. IL-36γ, FAP and EMT markers expression were evaluated by real-time polymerase chain reaction and western blot. Masson trichrome staining was adopted to assess tissue fibrotic changes. Furthermore, the soluble form of IL-36γ and FAP in nasal secretions was detected by ELISA. RESULTS: While basal expression of E-cadherin decreased, the expression of IL-36γ, vimentin and FAP increased in nasal polyps. In well-prognosis patients, the expression of IL-36γ, vimentin and FAP were significantly decreased than in poor-prognosis patients, while the protein expression of E-cadherin was increased. The protein expression of IL-36γ was notably increased in recurrent nasal polyps than in preoperation specimens. A positive relationship between IL-36γ and FAP expression, a negative relationship between IL-36γ and E-cad expression was noted. The soluble form of IL-36γ and FAP increased during the development of non-Eos CRSwNP, with the highest level in poor-prognosis patients after surgery. CONCLUSION: Non-Eos CRSwNP have partially undergone EMT under baseline conditions. IL-36γ and FAP expression were related with EMT, the soluble form of IL-36γ and FAP in nasal secretions may predict the prognosis of patients.

LAMC2 acts as a novel therapeutic target of cetuximab in laryngeal cancer.

This study was set out to determine the function of LAMC2 in laryngeal cancer (LC). Initially, we identified the expression of LAMC2 in LC cells and tissues using TCGA datasets, GEO datasets (GSE143224), qRT-PCR, and western blot. Besides, we analyzed the correlations between LAMC2 and clinicopathologic features in LC patients. The CCK-8 assays were performed to detect cell viability and the half-maximal inhibitory concentration of cetuximab (IC50) in LC cells. We explored the correlations between LAMC2 and EGFR and further explored the regulation mechanism of cetuximab in LC. This study identified a high expression of LAMC2 in LC cells and tissues. The expression levels of LAMC2 were associated with TNM classification, lymph node (LN) metastasis, differentiation, and overall survival (OS). LAMC2 significantly promoted cell proliferation and cell viability. Besides, cetuximab significantly inhibited LAMC2 expression levels. LAMC2 significantly reversed the effect of cetuximab suppressing cell proliferation in LC cells. In conclusion, LAMC2 may act as a novel anti-cancer target in LC.

Molecular dynamics simulations on RORγt: insights into its functional agonism and inverse agonism.

The retinoic acid receptor-related orphan receptor (ROR) γt receptor is a member of nuclear receptors, which is indispensable for the expression of pro-inflammatory cytokine IL-17. RORγt has been established as a drug target to design and discover novel treatments for multiple inflammatory and immunological diseases. It is important to elucidate the molecular mechanisms of how RORγt is activated by an agonist, and how the transcription function of RORγt is interrupted by an inverse agonist. In this study we performed molecular dynamics simulations on four different RORγt systems, i.e., the apo protein, protein bound with agonist, protein bound with inverse agonist in the orthosteric-binding pocket, and protein bound with inverse agonist in the allosteric-binding pocket. We found that the orthosteric-binding pocket in the apo-form RORγt was mostly open, confirming that apo-form RORγt was constitutively active and could be readily activated (ca. tens of nanoseconds scale). The tracked data from MD simulations supported that RORγt could be activated by an agonist binding at the orthosteric-binding pocket, because the bound agonist helped to enhance the triplet His479-Tyr502-Phe506 interactions and stabilized H12 structure. The stabilized H12 helped RORγt to form the protein-binding site, and therefore made the receptor ready to recruit a coactivator molecule. We also showed that transcription function of RORγt could be interrupted by the binding of inverse agonist at the orthosteric-binding pocket or at the allosteric-binding site. After the inverse agonist was bound, H12 either structurally collapsed, or reorientated to a different position, at which the presumed protein-binding site was not able to be formed.

Gamma-Aminobutyric Acid Increases the Production of Short-Chain Fatty Acids and Decreases pH Values in Mouse Colon.

Gamma-Aminobutyric acid (GABA) could regulate physiological functions in the gastrointestinal tract. The present study aimed to investigate the effect of GABA on colon health in mice. The female Kunming mice were given GABA at doses of 5, 10, 20 and 40 mg/kg/d for 14 days. Afterwards, the short-chain fatty acids (SCFAs) concentrations, pH values, colon index, colon length and weight of colonic and cecal contents were determined to evaluate the effects of GABA on colon health. The results showed that intake of GABA could increase the concentrations of acetate, propionate, butyrate and total SCFAs in colonic and cecal contents, as well as the weight of colonic and cecal contents. The colon index and length of the 40 mg/kg/d GABA-treated group were significantly higher than those of the control group (p < 0.05). In addition, decrease of pH values in colonic and cecal contents was also observed. These results suggest that GABA may improve colon health.

Structural Features of Alkaline Extracted Polysaccharide from the Seeds of Plantago asiatica L. and Its Rheological Properties.

Polysaccharide from the seeds of Plantago asiatica L. has many bioactivities, but few papers report on the structural and rheological characteristics of the alkaline extract. The alkaline extracted polysaccharide was prepared from seeds of P. asiatica L. and named herein as alkaline extracted polysaccharide from seeds of P. asiatica L. (PLAP). Its structural and rheological properties were characterized by monosaccharide composition, methylation, GC-MS and rheometry. PLAP, as an acidic arabinoxylan, was mainly composed of 1,2,4-linked Xylp and 1,3,4-linked Xylp residues. PLAP solution showed pseudoplastic behavior, and weak gelling properties at high concentration. Sodium and especially calcium ions played a significant role in increasing the apparent viscosity and gel strength.

Endoscopic prelacrimal recess approach adjunct with vestibular sulcus incision: case report of a minimally invasive access to remove infratemporal fossa tumor.

To remove tumor located at anterolateral-inferior of infratemporal fossa (ITF) with purely transnasal approach is still a great challenge because of the over lateral angulation. The aim of this study is to present our initial experience--endoscopic prelacrimal recess approach adjunct with vestibular sulcus incision as a simple and minimally invasive approach to remove tumor in this area. Tumor in anterolateral ITF can be well explored via endoscopic prelacrimal recess approach; a simple vestibular sulcus incision provides a second access for two-surgeon co-operation, so tumor can be removed conveniently with minimal invasion. It is a viable alternative to endoscopic extended medial maxillectomy approach or open approaches to this area.

Laryngo-tracheobronchial amyloidosis: a case report and review of literature.

AMYLOIDOSIS is a benign process which can have systemic involvement. Though larynx is the common site of localized amyloidosis in the head and neck region,1 it was seldom reported with heterochronous implication of bilateral ventricles. Here we report a case of laryngeal amyloidosis heterochronously localized at bilateral ventricles with tracheobronchial involvement. Combined with our experience we reviewed the literature, and discuss the pertinent managements of this condition.

The utility of repeated computed tomography to track a foreign body penetrating the esophagus to the level of the thyroid gland.

OBJECTIVE: Foreign body (FB) ingestion is a common problem in otolaryngology. One uncommon complication of FB ingestion is penetration to the level of the thyroid gland. To our knowledge, only 21 such cases have been reported in the literature. Here, we report a case of an esophageal FB penetrating to the level of the right thyroid gland. CASE REPORT: The patient was a 38-year-old woman in whom an esophageal FB penetrated to the level of the right thyroid gland. We traced the path to the thyroid gland using repeated computed tomography (CT) scans and demonstrated the importance of multiplanar reconstruction in locating the FB and formulating a precise surgical plan. CONCLUSIONS: To our knowledge, this is the first report of repeat CT scans being used to demonstrate the migratory route, over time, of a FB penetrating through the esophagus to the level of the thyroid gland. Our results suggest that multiplanar reconstruction may play a key role in the precise diagnosis of a FB at the level of the thyroid gland and may help surgeons choose the best approach for removal.

Mining and Validation of Novel Hemp Seed-Derived DPP-IV-Inhibiting Peptides Using a Combination of Multi-omics and Molecular Docking.

Hemp seed-derived inhibitors of dipeptidyl peptidase IV (DPP-IV) demonstrate potential as novel therapeutics for diabetes; however, their proteome and genome remain uncharacterized. We used multi-omics technology to mine peptides capable of inhibiting DPP-IV. First, 1261 and 1184 proteins were identified in fresh and dry hemp seeds, respectively. Simulated protease cleavage of dry seed proteins yielded 185,446 peptides for virtual screening to select the potential DPP-IV-inhibiting peptides. Sixteen novel peptides were selected according to their DPP-IV-binding affinity determined via molecular docking. In vitro DPP-IV inhibition assays identified the peptides LPQNIPPL, YPYY, YPW, LPYPY, WWW, YPY, YPF, and WS with half-maximal inhibitory concentration (IC50) values lower than 0.5 mM, which were 0.08 ± 0.01, 0.18 ± 0.03, 0.18 ± 0.01, 0.20 ± 0.03, 0.22 ± 0.03, 0.29 ± 0.02, 0.42 ± 0.03, and 0.44 ± 0.09 mM, respectively. The dissociation constants (KD) of the 16 peptides ranged from 1.50 × 10-4 to 1.82 × 10-7 M. Furthermore, Caco2 and INS-1 cell assays showed that all 16 peptides could efficiently inhibit DPP-IV activity and increase insulin and glucagon-like peptide-1 concentrations. These results demonstrate a well-established and efficient method to isolate food-derived therapeutic DPP-IV-inhibiting peptides.

Association Between Hemoglobin Glycation Index and Risk of Cardiovascular Disease and All Cause Mortality in Type 2 Diabetic Patients: A Meta-Analysis.

Background: The hemoglobin glycation index (HGI) has been proposed as a marker to quantify inter-individual variation in hemoglobin glycosylation. However, whether HGI is associated with an increased risk of diabetic complications independent of glycated hemoglobin (HbA1c) remains unclear. This meta-analysis aimed to determine the association between HGI and the risk of all cause mortality and composite cardiovascular disease (CVD). Methods: PubMed, and EMBASE databases were searched for related studies up to March 31, 2021. Observational studies reported associations between HGI levels and composite CVD and all cause mortality were included for meta-analysis. A random effect model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CI) for higher HGI. Results: A total of five studies, comprising 22,035 patients with type two diabetes mellitus were included for analysis. The median follow-up duration was 5.0 years. After adjusted for multiple conventional cardiovascular risk factors, an increased level of HGI was associated with a higher risk of composite CVD (per 1 SD increment: HR = 1.14, 95% CI = 1.04-1.26) and all cause mortality (per 1 SD increment: HR = 1.18, 95% CI = 1.05-1.32). However, when further adjusted for HbA1c, the association between HGI and risk of composite CVD (per 1 SD increment of HGI: HR = 1.01, 95% CI = 0.93-1.10) and all cause mortality (per 1 SD increment of HGI: HR = 1.03, 95% CI = 0.96-1.10) became insignificant. Conclusions: High HGI was associated with an increased risk of composite CVD and all cause mortality after adjustment for multiple conventional cardiovascular risk factors. However, the association was mainly mediating by the level of HbA1c.

Polysaccharides from fermented Momordica charantia L. with Lactobacillus plantarum NCU116 ameliorate metabolic disorders and gut microbiota change in obese rats.

Obesity is a chronic disease characterized by overweight resulting from fat accumulation, along with disturbance of metabolism and gut microbiota. Fermentation, as a green processing method, is beneficial for improving the nutrition capacity of food components. Polysaccharides are considered as one of the important components in food and are also potential supplements for anti-obesity treatment. This study aimed to investigate the anti-obesity effects of polysaccharides from fermented and non-fermented Momordica charantia L. with Lactobacillus plantarum NCU116 (FP and NFP) on obese rats by serum metabolomics and gut microbiota analysis. Metabolomics results revealed that abnormal lipid metabolism was formed due to obesity. The supplement of FP and NFP improved the glycerophospholipids, glycosphingolipids, and amino acid metabolism of the obese rats, which alleviated the hypercholesterolemia and overweight in rats. Furthermore, the disorder of gut microbiota was ameliorated by FP and NFP. FP promoted the growth of beneficial bacteria, such as phylum Firmicutes, Actinobacteria, and genera Anaerostipes, Coprococcus, Lactobacillus, and Bifidobacterium. FP also reduced several harmful bacteria belonging to the phylum Proteobacteria and genera Helicobacter. The positive correlation of the weight loss and lowering of serum lipids with the increased beneficial bacteria further elucidated that the anti-obesity effect of FP in obese rats is associated with the regulation of gut microbiota and serum metabolites. The results of this study could provide information for developing probiotic products in the future that may have beneficial effects on the prevention or treatment of obesity.

[Effect of edaravone on extracellular signal-regulated kinase 1/2 pathway following severe traumatic brain injury in rats].

OBJECTIVE: To study the protective effect of edaravone on severe traumatic brain injury (TBI) and its potential mechanism. METHODS: Two hundred and seventy-three male Sprague-Dawley (SD) rats were divided randomly into four groups: control group (n=45), model group (n=88), low-dose edaravone treatment group (n=72), high-dose edaravone treatment group (n=68). TBI rat model was reproduced by weight-dropping injury. One, 6, 24, 48 and 72 hours after injury, changes in brain tissue were observed with light and electron microscopy. The expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) was determined by Western blotting. The rate of neuron apoptosis was observed with immunohistochemistry and terminal-deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. Learning and memory function assessments were performed with Morris water maze from 7th day to 10th day after injury. RESULTS: Compared with control group, a part of neurons in hippocampus displayed histopathologic changes denoting necrosis 6, 24, 48 and 72 hours after injury. The p-ERK1/2 expression level (pg/unit) increased 1, 6, 24, 48 hours after injury (2.05 + or - 0.40, 4.40 + or - 0.96, 6.70 + or - 0.87, 3.67 + or - 0.28 vs. 0.40 + or - 0.04, 0.41 + or - 0.05, 0.43 + or - 0.06, 0.40 + or - 0.03), and the number of apoptotic cells increased 6, 24, 48, 72 hours after injury (9.60 + or - 2.69, 12.68 + or - 2.99, 16.94 + or - 3.92, 25.82 + or - 4.61 vs. 2.42 + or - 0.38, 2.58 + or - 0.57, 2.74 + or - 0.56, 2.61 + or - 0.58); latent period to find the safety platform (s) was significantly prolonged (119.8 + or - 25.0, 105.6 + or - 24.5, 98.5 + or - 21.8, 92.0 + or - 19.5 vs. 49.5 + or - 7.5, 32.7 + or - 6.3, 25.8 + or - 6.5, 24.8 + or - 5.5, all P<0.05). After treatment with edaravone, the degree of morphological injury, p-ERK1/2 level and number of apoptotic neurons decreased, latent period to find the safety platform was significantly shortened (in low-dose edaravone treatment group, p-ERK1/2 expression level at 6, 24, 48 hours was 2.46 + or - 0.22, 4.00 + or - 0.84, 2.38 + or - 0.32, and in high-dose edaravone treatment group was 1.67 + or - 0.15, 1.86 + or - 0.38, 1.27 + or - 0.28; in low-dose edaravone treatment group, the apoptotic cells at 6, 24, 48, 72 hours was 5.20 + or - 1.23, 7.10 + or - 1.72, 9.54 + or - 1.36, 14.12 + or - 3.19, and in high-dose edaravone treatment group was 3.40 + or - 0.49 , 4.39 + or - 0.73, 5.02 + or - 1.12, 8.78 + or - 2.16; in low-dose edaravone treatment group, latent period to find the safety platform at 7-10 days was 94.8 + or - 22.8, 65.2 + or - 19.0, 62.0 + or - 16.7, 59.5 + or - 15.6, and in high-dose edaravone treatment group it was 81.5 + or - 20.7, 55.4 + or - 18.5, 40.0 + or - 12.3, 32.2 + or - 11.0, all P<0.05). High-dose edaravone showed a better effect (all P<0.05). CONCLUSION: Edaravone gives good therapeutic effect on severe TBI, and the molecular mechanism is related to attenuation of ERK1/2 pathway and neuronal apoptosis following severe brain trauma.

Protective effect of three glucomannans from different plants against DSS induced colitis in female BALB/c mice.

Glucomannans (GMs) from diverse natural plants have great potentiality in enhancing the host immune system. The protective effects of three GMs on the intestinal mucosal immunity in colitis mice were investigated and compared in this study. The three GMs (KGM, AGP, and DOP) were obtained from Amorphophallus rivieri, Aloe vera, and Dendrobium officinale, respectively, having different weight-averaged molecular weights (Mw), acetyl group content, and molar ratios of mannose to glucose (M/G). The three fractions were administered with or without dextran sodium sulfate (DSS) containing drinking water. Macroscopic observations (health state, crypt depth, and bowel thickness of colon tissue) were conducted. Furthermore, related cytokines and mRNA expressions of TLRs were measured by ELISA and RT-qPCR, respectively. Results showed that the administration of the three GMs improved the health state of colitis mice, such as the recovery of body weight, and the increase of the immune organ index, crypt depth, bowel wall thickness, and total number of immune cells. The integrity of intestinal mucosa was maintained by the increased number of goblet cells and mucin protein production. Further studies showed that GMs kept the balance between pro- and anti-inflammatory cytokines and also regulated the expressions of TLR-2, TLR-4, TLR-6, and TLR-9. The above results suggested that GMs could attenuate the intestinal epithelial injury and regulate the intestinal mucosal immunity. Structural features including the M/G ratio, Mw, and the content of acetyl groups jointly influence the protective effects of GMs on the colitis mice.

Fermented Momordica charantia L. juice modulates hyperglycemia, lipid profile, and gut microbiota in type 2 diabetic rats.

The effect of Lactobacillus plantarum-fermentation on the anti-diabetic functionality of Momordica charantia was examined using a high-fat-diet and low-dose streptozocin-induced type 2 diabetic rat model. Fermented Momordica charantia juice (FMCJ) administration mitigated the hyperglycemia, hyperinsulinemia, hyperlipidemia, and oxidative stress in diabetic rats more favorably than the non-fermented counterpart. Treatments with FMCJ improved ergosterols and lysomonomethyl-phosphatidylethanolamines metabolisms more effectively. Supplement of FMCJ regulated the composition of the gut microbiota, such as increased the abundance of Bacteroides caecigallinarum, Oscillibacter ruminantium, Bacteroides thetaiotaomicron, Prevotella loescheii, Prevotella oralis, and Prevotella melaninogenica, in diabetic rats compared with untreated diabetic rats. Moreover, FMCJ-treated diabetic rats exhibited higher concentrations of acetic acid, propionic acid, butyric acid, total short-chain fatty acids and lower pH values in colonic contents than that in non-fermented juice-treated rats. These results demonstrated that Lactobacillus plantarum-fermentation enhanced the anti-diabetic property of MC juice by favoring the regulation of gut microbiota and the production of SCFAs.

Polysaccharides from fermented Momordica charantia ameliorate obesity in high-fat induced obese rats.

Momordica charantia (M. charantia) has been widely used to treat obesity due to its bioactive ingredients. This research aimed to investigate the anti-obesity effect of polysaccharides (FP) from fermented M. charantia with Lactobacillus plantarum NCU116 on high-fat induced obese rats. We found that FP could effectively lower the body weight gain, Lee's index, insulin resistance and cell sizes of epididymal adipose tissues in obese rats compared with polysaccharides from non-fermented M. charantia (NFP). FP treatments decreased the total cholesterol, triacylglycerols, and low-density lipoprotein cholesterol, leptin, whereas they elevated the high-density lipoprotein cholesterol, adiponectin, significantly in the serum of obese rats. Furthermore, administrations of FP notably improved oxidative balance in obese rats. Lipidomics results indicated that 24 potential biomarkers have been identified in serum. Additionally, 21 lipids were considerably altered by FP and NFP intakes, such as fatty acyls, glycerolipids, sphingolipids, sterol lipids and glycerophospholipids. The anti-obesity properties of FP were revealed via relieving insulin resistance and fat accumulation of obese rats, which was associated with the regulation of lipid metabolism. Overall, FP exerted more favourable impacts on the anti-obesity effect than NFP, which may be attributed to fermentation.

Physicochemical, functional and emulsion properties of edible protein from avocado (Persea americana Mill.) oil processing by-products.

Avocado (Persea americana) is a tropical fruit that has drawn great interest its oil for foods and cosmetic industries; however, avocado oil processing by-product is a potential source of edible protein. Herein, edible protein was prepared from defatted avocado meal, and it's physicochemical, functional and emulsion properties were investigated. The avocado protein showed U-shaped exhibiting strong effect of pH, and a minimum solubility being observed at pH 4.5, confirming the isoelectric point of avocado protein. Nutritionally, the avocado protein contains all the essential amino acids. Avocado protein provided higher water and oil absorption capacities, higher radical scavenging capacity but lower in-vitro digestibility compared with soy protein. Furthermore, the avocado protein as emulsifier afforded a stability oil-in-water emulsion system, resulting in a greater emulsifying stability than that of soy protein. The present results highlight the potential source of edible protein from avocado oil processing by-products for functional food ingredients.

Transnasal endoscopic repair of acquired posterior choanal stenosis and atresia.

BACKGROUND: There are congenital and acquired choanal atresias and many approaches have been used for their repair. We assessed the clinical effect of power instrument, endoscopic repair of acquired choanal stenosis and atresia. METHODS: Nineteen patients, aged from 32 to 61 years, with acquired choanal stenosis and atresia (from trauma in 5 cases and from radiotherapy after nasopharyngeal carcinoma in 14; 6 bilateral and 13 unilateral cases), underwent transnasal endoscopic repair of choanal stenosis and atresia. No patient had stenting. Antibiotic and local glucocorticoid were administered postoperatively. RESULTS: Eighteen patients remained free of symptoms for 12 - 40 months after the surgery, and the diameter of the neochoana was more than 1 cm after the procedure. One patient required revision surgery and recovered completely with no restenosis at 12 months after the second surgery. There were no postoperative complications. Histology of the resected tissue revealed respiratory epithelial-lined stromal tissue with chronic inflammation, edema and fibrosis, but no tumor cells. CONCLUSIONS: Transnasal endoscopic approach is a useful procedure for the repair of acquired choanal stenosis and atresia: it is highly successful, safe and effective with swift recovery and short time of hospitalization. It is very important in postoperative care to remove any granulation or polyps at the site of the neochoana at that time.

[Clinical significance of angiopoietin-2 expression in oral squamous cell carcinoma].

OBJECTIVE: To investigate the expression of angiopoietin-2 (Ang-2) and its clinical significance in oral squamous cell carcinoma. METHODS: The expression of Ang-2 mRNA was measured by real-time RT-PCR, and the expression of Ang-2 protein in tissue samples was detected by immunohistochemical staining. RESULTS: The mean dCt value of Ang-2 mRNA expression in the cancer tissue was 6.86 +/- 1.37, significantly lower than that in the paired adjacent non-cancerous tissue (7.95 +/- 2.08, P < 0.05), indicating a significantly higher expression of Ang-2 mRNA in the cancerous tissue than that in the adjacent non-cancerous tissue. The distribution of Ang-2 protein was found not only in the vascular endothelial cells but also in tumor cells. Semi-quantitative analysis revealed that the expression of Ang-2 protein in tumor specimens (53.6%) was significantly higher than that (24.0%) in the paired adjacent non-cancerous tissue (P < 0.05), the result was well consistent with that measured by RT-PCR. The dCt value of Ang-2 mRNA expression was 6.48 +/- 1.16 in the patients with metastasis in lymph nodes versus 7.16 +/- 1.49 in those without, with a non-significant difference between the two groups (P > 0.05). As regards the clinical stages, no significant difference was found between the expressions of Ang-2 mRNA in stage I + II (7.11 +/- 1.63) and stage III + IV cases (6.49 +/- 1.10, P > 0.05). CONCLUSION: Angiopoietin-2 protein is expressed not only in vascular endothelial cells, but also in tumor cells, suggesting that angiopoietin-2 may take part in angiogenesis in oral squamous cell carcinoma. However, our results that high expression of angiopoietin-2 mRNA is not correlated with lymph node metastasis and clinical stages, needs to be further verified in a large scale study.

Genistein Promotes Proliferation of Human Cervical Cancer Cells Through Estrogen Receptor-Mediated PI3K/Akt-NF-κB Pathway.

Phytoestrogens are polyphenol compounds which have similar structure to 17ß-estradiol (E2), a kind of main estrogen in women. Thus, phytoestrogens may affect the reproductive and endocrine systems, leading to the development of estrogen-related cancers. The effect of genistein (Gen), one of the most studied phytoestrogens, on human cervical cancer cells (HeLa) was investigated in this study. It was found that Gen at concentrations of 0.001, 0.01, 0.1 and 1 µmol·L-1 promoted the proliferation of HeLa cells in a dose-dependent manner. Gen increased the portion of HeLa cells in S phase and decreased the portion of the cells in G1 phase. Besides, apoptosis rate of the cells was significantly lower when treated with Gen compared with the control group. It was also found that the expression of ERα, Akt or nuclear NF-κB p65 protein was activated by Gen. The correlation between these three proteins may be as following: ERα was the upstream, followed by Akt, and then nuclear NF-κB p65 protein. In addition, the downstream genes of activated nuclear NF-κB p65 were found to be associated with cell cycle and apoptosis of cancer cells. Our results suggested that Gen may stimulate cell proliferation partially through the estrogen receptor-mediated PI3K/Akt-NF-κB pathway and the further activation of the downstream genes of nuclear NF-κB p65.

Polysaccharide from fermented Momordica charantia L. with Lactobacillus plantarum NCU116 ameliorates type 2 diabetes in rats.

The influence of Lactobacillus plantarum-fermentation on the structure and anti-diabetic effects of Momordica charantia polysaccharides were evaluated. High-fat diet and streptozotocin-induced type 2 diabetic rats were administrated with polysaccharides from fermented and non-fermented Momordica charantia (FP and NFP) for 4 weeks. Fermentation affected the physicochemical characterization, monosaccharide composition, molecular weight, and viscosity of Momordica charantia polysaccharides. Treatment with FP significantly ameliorated hyperglycemia, hyperinsulinemia, hyperlipidemia, and oxidative stress in diabetic rats compared with NFP. Moreover, the diversity and abundance of gut microbiota (Lactococcus laudensis and Prevotella loescheii) in diabetic rats were notably increased by treatment with FP in comparison to NFP. Meanwhile, FP-treated diabetic rats exhibited more colonic short-chain fatty acids (SCFAs) and lower pH values than that in NFP-treated rats. Overall, Lactobacillus plantarum-fermentation could enhance the anti-diabetes effects of Momordica charantia polysaccharides in rats by modifying the structure of polysaccharides to optimize gut microbiota and heighten the production of SCFAs.