Wound-healing properties of Stryphnodendron adstringens (barbatimão) in skin and mucosa injuries: a scoping review protocol.

OBJECTIVE: This review will map the literature on the types of research and methods used to investigate the wound-healing properties of Stryphnodendron adstringens ( barbatimão ) in skin and mucosa injuries. INTRODUCTION: Barbatimão is a Brazilian native plant and its wound-healing properties have been described in literature since the colonial period. It is one of the 71 plants included in the Brazilian health system's national list of medicinal plants of interest. However, existing literature reviews on the subject are limited, not comprehensive, lack a search strategy, and lack peer review. INCLUSION CRITERIA: This scoping review will include all types of published and unpublished sources that investigate the wound-healing properties of barbatimão to treat any type of skin or mucosa injury in humans, animals, or in vitro, in any context. METHODS: A scoping review will be conducted following JBI methodology. The main databases to be searched will include Embase (EBSCOhost), CINAHL (EBSCOhost), Scopus, PubMed (EBSCOhost), ScienceDirect, Lilacs, SciELO, CUIDEN, MOSAICO, Web of Science, Epistemonikos, and Google Scholar. Unpublished studies will also be considered. Two independent reviewers will examine titles and abstracts and select and read full-text sources for possible inclusion. Subsequently, the reviewers will extract and synthesize the data, which will be presented as a map, diagram, or table, according to the review objectives. REVIEW REGISTRATION: Open Science Framework osf.io/w57m4.

Cationic Nanoemulsion-Encapsulated Retinoic Acid as an Adjuvant to Promote OVA-Specific Systemic and Mucosal Responses.

Cationic nanostructures have emerged as an adjuvant and antigen delivery system that enhances dendritic cell maturation, ROS generation, and antigen uptake and then promotes antigen-specific immune responses. In recent years, retinoic acid (RA) has received increasing attention due to its effect in activating the mucosal immune response; however, in order to use RA as a mucosal adjuvant, it is necessary to solve the problem of its dissolution, loading, and delivery. Here, we describe a cationic nanoemulsion-encapsulated retinoic acid (CNE-RA) delivery system composed of the cationic lipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOTAP), retinoic acid, squalene as the oil phase, polysorbate 80 as surfactant, and sorbitan trioleate 85 as co-surfactant. Its physical and chemical properties were characterized using dynamic light scattering and a spectrophotometer. Immunization of mice with the mixture of antigen (ovalbumin, OVA) and CNE-RA significantly elevated the levels of anti-OVA secretory immunoglobulin A (sIgA) in vaginal lavage fluid and the small intestinal lavage fluid of mice compared with OVA alone. This protocol describes a detailed method for the preparation, characterization, and evaluation of the adjuvant effect of CNE-RA.

Cistanche deserticola polysaccharide-functionalized dendritic fibrous nano-silica as oral vaccine adjuvant delivery enhancing both the mucosal and systemic immunity.

Oral vaccines are a safe and convenient alternative to injected vaccines and have great potential to prevent major infectious diseases. However, the harsh gastrointestinal (GI) environment, mucus barriers, low immunogenicity, and lack of effective and safe mucosal adjuvants are the major challenges for oral vaccine delivery. In recent years, nanoparticle-based strategies have become attractive for improving oral vaccine delivery. Here, the dendritic fibrous nano-silica (DFNS) grafted with Cistanche deserticola polysaccharide (CDP) nanoparticles (CDP-DFNS) were prepared and investigated how to impact the immune responses. CDP-DFNS facilitated the antigen uptake in mouse bone marrow-derived dendritic cells (BMDCs), and induce the activation of DCs in vitro. Furthermore, in vivo experiments, the result showed that the uptake efficiency by Peyer's patches (PPs) of CDP-DFNS/BSA was the best. And CDP-DFNS/BSA then significantly activated the DCs in lamina propria (LP), and T/B cells in PPs and mesenteric lymph nodes (MLNs). Moreover, the memory T cell responses in later period of vaccination was stronger than other groups. In addition, CDP-DFNS/BSA enhanced BSA-specific antibody IgG, IgA production, and SIgA secretion, was effective at inducing a strong mixed Th1/Th2 response and mucosal antibody responses. These results indicated that CDP-DFNS deserves further consideration as an oral vaccine adjuvant delivery system.

Transient Mild Photothermia Improves Therapeutic Performance of Oral Nanomedicines with Enhanced Accumulation in the Colitis Mucosa.

The treatment outcomes of oral medications against ulcerative colitis (UC) have long been restricted by low drug accumulation in the colitis mucosa and subsequent unsatisfactory therapeutic efficacy. Here, high-performance pluronic F127 (P127)-modified gold shell (AuS)-polymeric core nanotherapeutics loading with curcumin (CUR) is constructed. Under near-infrared irradiation, the resultant P127-AuS@CURs generate transient mild photothermia (TMP; ≈42 °C, 10 min), which facilitates their penetration through colonic mucus and favors multiple cellular processes, including cell internalization, lysosomal escape, and controlled CUR release. This strategy relieves intracellular oxidative stress, improves wound healing, and reduces immune responses by polarizing the proinflammatory M1-type macrophages to the anti-inflammatory M2-type. Upon oral administration of hydrogel-encapsulating P127-AuS@CURs plus intestinal intralumen TMP, their therapeutic effects against acute and chronic UC are demonstrated to be superior to those of a widely used clinical drug, dexamethasone. The treatment of P127-AuS@CURs (+ TMP) elevates the proportions of beneficial bacteria (e.g., Lactobacillus and Lachnospiraceae), whose metabolites can also mitigate colitis symptoms by regulating genes associated with antioxidation, anti-inflammation, and wound healing. Overall, the intestinal intralumen TMP offers a promising approach to enhance the therapeutic outcomes of noninvasive medicines against UC.

Comparison between Organic and Inorganic Zinc Forms and Their Combinations with Various Dietary Fibers in Respect of the Effects on Electrolyte Concentrations and Mucosa in the Large Intestine of Pigs.

This study aimed to determine the effects of Zn sources, used with potato fiber (PF) or lignocellulose (LC), on electrolyte concentration and the mucus layer in the large intestine of pigs. The experiment involved 24 barrows with an initial body weight of 10.8 ± 0.82 kg, divided into four groups fed the following diets: LC and ZnSO4, LC and Zn glycinate (ZnGly), PF and ZnSO4, or PF and ZnGly. Fiber supplements provided 10 g crude fiber/kg diet, while Zn additives introduced 120 mg Zn/kg diet. After four weeks of feeding, the pigs were sacrificed and digesta and tissue samples were taken from the cecum and colon. PF increased the water content and decreased the phosphorus concentration in the large intestine in comparison with LC. PF also increased calcium, iron, and chloride concentrations in the descending colon. Mucus layer thickness and histological parameters of the large intestine were not affected. ZnGly diets increased MUC12 expression in the cecum as compared to the LC-ZnSO4 group. In the ascending colon, the PF-ZnGly diet increased MUC5AC expression, while both PF groups had greater MUC20 expression in comparison with the LC-ZnSO4 group. In the transverse colon, the LC-ZnGly group and both PF groups had higher MUC5AC expression in comparison with the LC-ZnSO4 group, and both ZnGly groups had higher MUC20 expression than ZnSO4 groups. PF and ZnGly increased MUC4 and MUC5AC expression in the descending colon. PF and ZnGly may exert a beneficial effect on colon health in pigs by upregulating the expression of the MUC5AC and MUC20 genes and are more effective than LC and ZnSO4.

[PKEP with complete preservation of the urethral mucosa in the 11－1 o'clock position improves urinary continence and protects erectile function in BPH patients].

OBJECTIVE: To evaluate the effect of transurethral plasmakinetic enucleation of the prostate (PKEP) with complete preservation of the urethral mucosa in the 11－1 o'clock position on urinary continence and erectile function in BPH patients. METHODS: We retrospectively analyzed the clinical data on 84 cases of BPH treated by traditional PKEP (group A, n = 48) or modified PKEP with complete preservation of the urethral mucosa in the 11－1 o'clock position (group B, n = 36) from January 2017 to December 2021. All the patients had sexual activities within three months preoperatively. We followed up the patients for 12 months after surgery and compared the baseline, surgery-related and follow-up data between the two groups of patients. RESULTS: There were no statistically significant differences between the two groups of patients in age, disease duration, prostate volume, preoperative postvoid residual urine (PVR), preoperative maximum urinary flow rate (Qmax), IPSS, PSA level, QOL scores or IIEF-5 scores, nor in the operation time, intraoperative hemoglobin decrease, volume of resected tissue, bladder flushing time, postoperative hospital stay, or postoperative improvement of Qmax and IPSS. The rate of urinary continence was significantly higher in group B than in A at 1 month postoperatively (66.67% ï¼»24/36ï¼½ vs 43.25% ï¼»20/48ï¼½, P = 0.025) and so were IIEF-5 scores at 6 months (16.69 ± 3.21 vs 15.27 ± 2.74, P = 0.032) and 12 months (18.04 ± 2.04 vs 16.96 ± 2.54, P = 0.039), while the incidence rate of retrograde ejaculation markedly lower in the former than in the latter group at 6 months (33.33% ï¼»12/36ï¼½ vs 56.25% ï¼»28/48ï¼½, P = 0.018) and 12 months (25% ï¼»9/36ï¼½ vs 47.92% ï¼»23/48ï¼½, P = 0.027). At 1, 3, 6 and 12 months after surgery, the patients in group B also showed remarkably higher QOL scores than those in group B (2.61 ± 0.81 vs 2.12 ± 0.69, P = 0.005; 2.24 ± 0.66 vs 1.94 ± 0.51,P = 0.026; 2.12 ± 0.83 vs 1.80 ± 0.53,P = 0.047; and 1.94 ± 0.65 vs 1.72 ± 0.58, P = 0.038). CONCLUSION: Modified PKEP with complete preservation of the urethral mucosa in the 11－1 o'clock position can improve urinary continence, protect erectile function and ameliorate QOL in patients with BPH.

Comparison of pharmacological activity and safety of different stereochemical configurations of borneol: L-borneol, D-borneol, and synthetic borneol.

BACKGROUND: Chiral drugs generally exhibit differences in activity because they bind differently to their target receptor. The Chinese medicine borneol ('Bing Pian' in Chinese) is a bicyclic monoterpenoid with a wide range of biological activities. Three kinds of Chinese medicines comprising borneol are used clinically, namely, L-Borneolum ('Ai Pian' in Chinese), Borneolum ('Tian Ran Bing Pian' in Chinese), and synthetic borneol ('He Cheng Bing Pian' in Chinese). The three kinds of borneol have different stereochemical configurations, but their clinical uses are nearly identical, and their prices vary widely. However, there is no clear rational basis for the selection of these kinds of borneol in clinical applications. PURPOSE: The purpose of this study was to clarify differences in the biological activity, safety, and structure-activity relationship of the three kinds of borneol. METHODS: 'borneol', 'Bing Pian', 'Ai Pian', 'Tian Ran Bing Pian', and 'He Cheng Bing Pian' were selected as keywords to search for and extract relevant literature in the CNKI, PubMed, and Google Scholar databases up to November 2022. RESULTS: L-borneol has better potential in cerebrovascular diseases. The three kinds of borneol have stronger penetration-promoting effects on hydrophilic drugs. L-borneol and isoborneol promote intestinal mucosal absorption of drugs via bidirectional regulation of P-glycoprotein. D-borneol exhibits better antitumour sensitizing effects than L-borneol. L-borneol exhibits better inhibition of bacterial adhesion because of its C2 chiral centre. Synthetic borneol is less safe. CONCLUSION: L-borneol has excellent potential in many aspects, has various sources, and can effectively replace expensive D-borneol in some applications.

Gut distress and intervention via communications of SARS-CoV-2 with mucosal exposome.

Acute coronavirus disease 2019 (COVID-19) has been associated with prevalent gastrointestinal distress, characterized by fecal shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA or persistent antigen presence in the gut. Using a meta-analysis, the present review addressed gastrointestinal symptoms, such as nausea, vomiting, abdominal pain, and diarrhea. Despite limited data on the gut-lung axis, viral transmission to the gut and its influence on gut mucosa and microbial community were found to be associated by means of various biochemical mechanisms. Notably, the prolonged presence of viral antigens and disrupted mucosal immunity may increase gut microbial and inflammatory risks, leading to acute pathological outcomes or post-acute COVID-19 symptoms. Patients with COVID-19 exhibit lower bacterial diversity and a higher relative abundance of opportunistic pathogens in their gut microbiota than healthy controls. Considering the dysbiotic changes during infection, remodeling or supplementation with beneficial microbial communities may counteract adverse outcomes in the gut and other organs in patients with COVID-19. Moreover, nutritional status, such as vitamin D deficiency, has been associated with disease severity in patients with COVID-19 via the regulation of the gut microbial community and host immunity. The nutritional and microbiological interventions improve the gut exposome including the host immunity, gut microbiota, and nutritional status, contributing to defense against acute or post-acute COVID-19 in the gut-lung axis.

Integrated transcriptomics and lipidomics investigation of the mechanism underlying the gastrointestinal mucosa damage of Loropetalum chinense (R.Br.) and its representative component.

BACKGROUND: Loropetalum chinensis (R.Br) Oliv (Bhjm), a Chinese folk herbal medicine, was traditionally used in the treatment of wound bleeding and skin ulcers. A new drug named JIMUSAN granules used for gastrosia was developed by our group, and clinical trials have been approved. However, as the principal herb, the material basis and underlying mechanisms of Bhjm in attenuating gastrointestinal mucosa damage (GMD) remain to be systemically illuminated. PURPOSE: An integrated strategy was used to explore the therapeutic effects and mechanisms of Bhjm and ellagic acid (EA) on GMD zebrafish, using network pharmacology, transcriptomics, lipidomics, and real-time quantitative PCR (RT-qPCR) verification. METHODS: First, network pharmacological analysis was used to infer the major effective constituents and targets of Bhjm. Ultra high performance liquid chromatography-linear ion trap/orbitrap high resolution mass spectrometry (UHPLC-LTQ-Orbitrap HRMS) and ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) were employed to identify the chemical constituents and quantify the different types of constituents. Second, zebrafish model of GMD was established by using 2,4,6-trinitrobenzenesulfonic acid (TNBS) to evaluate the efficacy of Bhjm and EA. The potential mechanism was examined by integrated transcriptomics and lipidomics analysis. Finally, validation tests were implemented using RT-qPCR. RESULTS: In this study, targets indentified by network pharmacology were related to inflammation and mucosal damage. Ten representative components that interacted with these targets were simultaneously determined by UHPLC-MS/MS. Sixty four compounds were identified or tentatively characterized, most of which were flavonoids and polyphenols. Bhjm and EA alleviated mucosal damage and reduced inflammation in a TNBS-induced zebrafish GMD model, indicating that EA was the main active compounds. Eight common differentially expressed genes were downregulated by Bhjm and EA, as determined by transcriptomics analysis. Lipidomics analysis confirmed 12 differential lipids, including phosphatidylcholine (PC) and triglyceride (TG). Further network enrichment analysis demonstrated that differential lipid metabolism was regulated by klf4 and hist1h2ba, and were validated by RT-qPCR. CONCLUSION: In our study, the chemical profile of Bhjm was clarified. Moreover, the GMD repair effect and the mechanism of Bhjm and EA was comprehensively analyzed for the first time, involving inflammation and lipid metabolism. Collectively, these findings will be significantly helpful for deeply exploring the clinical application value of Bhjm.

Wei-Tong-Xin ameliorated cisplatin-induced mitophagy and apoptosis in gastric antral mucosa by activating the Nrf2/HO-1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Wei-Tong-Xin (WTX) originated from the famous ancient Chinese formula "Wan Ying Yuan", recorded in the ancient Chinese medicine book "Zhong Zang Jing" by Hua Tuo. As "Jun" drugs, Dahuang and Muxiang have the effects of clearing heat and expelling fire, reducing food retention, regulating Qi and relieving pain. As "Chen" drug, Qianniuzi has the effect of assisting "Jun" drugs. Zhuyazao and Gancao, as "Zuo-Shi" drugs, can reduce toxicity and modulate the medicinal properties of other herbs. AIM OF THE STUDY: The present study aimed to investigate the effect and mechanism of WTX on the oxidative stress of gastric antrum mucosa in mice with cisplatin (CIS)-induced dyspepsia. MATERIALS: AND. METHODS: A variety of experimental methods, including western blot, qRT-PCR, immunofluorescence and immunohistochemistry were performed in vivo and in vitro. RESULTS: In vivo, WTX restored the number and function of interstitial cells of Cajal (ICCs), accompanied by the inhibition of lipid peroxidation. Moreover, WTX inhibited the activation of Parkin-dependent mitophagy and apoptosis. In vitro, WTX activated the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway and inactivated mitophagy in GES-1 cells. To explore the role of Nrf2 in WTX's improvement of CIS-induced cell damage, Nrf2 inhibitor ML385 was used in cell experiments. We found that ML385 counteracted the regulation of WTX on mitophagy and apoptosis. Finally, N-acetylcysteine (NAC), a reactive oxygen species (ROS) scavenger, was applied in our experiments, and the results suggested that WTX suppressed the CIS-induced apoptosis via mitochondrial pathway. CONCLUSIONS: The above results, for the first time, indicated that WTX inhibited mitophagy and apoptosis of gastric antral mucosal cells induced by CIS through the Nrf2/HO-1 signaling pathway.

Comparison of mucosal phosphatase activity, phytate degradation, and nutrient digestibility in 3-week-old turkeys and broilers at different dietary levels of phosphorus and phytase.

A comparison between 3-wk-old female turkeys (B.U.T. 6) and broilers (Ross 308) was performed to study the effects of species, dietary P, Ca, and phytase levels on gut mucosal phosphatase activity, myo-inositol hexakisphosphate (InsP6) degradation along the digestive tract, digestibility of P, Ca, and amino acids, and concentrations of myo-inositol in the digesta and blood. The experimental diets were corn-soybean meal-based and identical for both species. Two dietary P and Ca concentrations (CaP-: 4.1 g P/kg, 5.5 g Ca/kg and CaP+: 9.0 g P/kg, 12.0 g Ca/kg) and 2 levels of phytase supplementation (0 and 1,500 FTU/kg) were used in a 2 × 2 factorial design and fed to the animals for 7 d in their third week of age. Each diet was randomly assigned to 6 broiler and 6 turkey pens, with 10 birds each. After slaughter, blood, digesta from the crop, gizzard, duodenum, lower ileum, and mucosa from the jejunum were collected. When fed CaP- without phytase supplementation, there were no differences between species in gut mucosal phosphatase activity, prececal InsP6 disappearance, and P and Ca digestibility, indicating a similar intrinsic capacity for phytate degradation in both species. When fed CaP+ without phytase supplementation, turkeys showed higher prececal InsP6 disappearance than broilers. Phytase supplementation increased prececal InsP6 disappearance and digestibility of P and Ca in both species. However, the phytase-induced increase in prececal InsP6 disappearance was more pronounced in broilers than in turkeys, possibly due to more adequate conditions for phytase activity in the broiler crop. In broilers, phytase supplementation increased amino acid digestibility overall, whereas, in turkeys, it increased with CaP+ and decreased with CaP-. In addition, the relationship between myo-inositol concentration in the ileum and blood differed between species, indicating differences in myo-inositol metabolism. It was concluded that 3-week-old turkeys and broilers differ in nutrient digestibility and InsP degradation in some segments of the digestive tract but have similar endogenous InsP6 degradation when fed low P and Ca diets.

Mucosal phosphatase activity, phytate degradation, and mineral digestibility in 6-week-old turkeys and broilers at different dietary levels of phosphorus and phytase and comparison with 3-week-old animals.

Female turkeys (B.U.T. 6) and broilers (Ross 308) were compared at 6 wk of age to evaluate the effects of species, dietary P, Ca, and phytase levels on myo-inositol hexakisphosphate (InsP6) degradation along the digestive tract, gut mucosal phosphatase activity, P and Ca digestibility, and myo-inositol concentrations in the digesta and blood. The environmental conditions and experimental corn-soybean meal-based diets were the same for both species. Four diets with either combination of 2 levels of P and Ca (CaP-: 4.0 g P/kg, 5.4 g Ca/kg and CaP+: 6.0 g P/kg, 8.0 g Ca/kg) and 2 levels of phytase supplementation (0 and 1,500 FTU/kg) were fed to the animals for 7 d at their sixth wk of age. Each diet was randomly assigned to 6 pens per species, with 10 birds each. After slaughter, blood, digesta from the crop, gizzard, duodenum, lower ileum, and jejunal mucosa were collected. Endogenous mucosal phosphatase activity in the jejunum was higher in turkeys than in broilers. Prececal InsP6 disappearance was also higher in turkeys than in broilers when phytase was not supplemented. Phytase supplementation led to a higher prececal InsP6 disappearance in broilers than in turkeys, likely due to different crop conditions such as moisture content. However, prececal P digestibility was higher in turkeys than broilers. Different relationships between myo-inositol concentration in the ileum digesta and blood were found, depending on the species. A comparison of the results with those obtained in 3-wk-old birds of a companion study showed that in diets with low Ca and P levels, prececal InsP6 disappearance increased with age in turkeys, but not in broilers. This coincided with changes in the conditions of the digestive tract, such as the water content in the crop, gizzard pH, and mucosal phosphatase activity. In conclusion, occurrence of differences in phytate degradation between turkeys and broilers, fed the same feed, depended on age and can be explained by different physiological development of the digestive tract.

The T stage of esophageal cancer can be effectively predicted by muscularis propria thickness and muscularis propria + mucosa thickness under ultrasonic gastroscopy.

OBJECTIVES: The latest version of the National Comprehensive Cancer Network recommends neoadjuvant therapy followed by surgical treatment or radical chemoradiotherapy for patients with cT3N0M0. Neoadjuvant therapy can improve the prognosis of patients with locally advanced esophageal cancer. Therefore, the evaluation or prediction of T stage is particularly important because the treatment could differently affect the prognosis. Here, we establish a model to predict the T stage of patients with T2-3N0M0 to help choose the best treatment strategy. METHODS: From 1637 patents with esophageal cancer, we enrolled 48 patients and performed least absolute shrinkage and selection operator regression to screen for independent factors influencing pathological T stage. We, then, trained the decision tree to obtain the decision tree diagram and divided the T stages obtained by different methods into two categories, T2 and T3, for survival analysis. RESULTS: A total of 21 and 27 cases were predicted to be T2 and T3, respectively, under ultrasonic gastroscopy, 19 and 29 under magnetic resonance imaging, and 22 and 26 under pathological examination. Multivariate logistic regression analysis revealed that the muscularis propria thickness (MPT) (p = 0.0097) and the muscularis propria + mucosa thickness (MPMT) in the largest tumor cross-section (p = 0.0239) were independent influencing factors. We plotted a decision tree diagram with these two factors. MPT in the largest tumor cross-section >1.3 mm could be judged as pT3; if ≤1.3 mm, MPMT should be considered a thickness ≥1.7 mm could be judged as pT2 (otherwise pT3). Corresponding survival analysis was performed according to the T stage under different examination modalities. CONCLUSION: MPT in the largest tumor cross-section and MPMT in the largest tumor cross-section are independent predicting factors of pathological T stage.

Secondary lesions of the mucous membrane of the oral cavity as a side effect of complex anticancer treatment: a literature review.

Today, both Ukraine and the world at large are faced with a significant number of oncological diseases with various localizations. The current state of diagnosis, prevention, early detection, and access to treatment leads to a substantial number of people in each country's healthcare system who require comprehensive cancer treatments. Modern medical and diagnosis protocols in oncology involve the usage of ionizing radiation and aggressive toxic chemotherapeutic agents which can significantly disrupt the physiology of the mucous membrane of the digestive tract during treatment, especially of the oral cavity. The most common complication of complex anticancer therapy is the development of various lesions of the oral cavity, including mucositis, which harms the patient's quality of life, limits the doses of chemotherapy and radiation therapy the patient can receive, and also negatively affects the effectiveness of complex therapy treatment. Acute oral mucositis is observed among almost 100% of treatment cases. This is a significant problem for clinical oncology as it may also reduce patient compliance with comprehensive anticancer treatment. The results indicate the presence of oral problems in 100% of patients receiving specialized antitumor chemotherapy and radiotherapy, as well as the presence of a high need for specialized dental treatment.

Guben Tongluo Formula Protects LPS-induced Damage in Lamina Propria B Lymphocytes Through TLR4/MyD88/NF-κB Pathway.

OBJECTIVE: The main pathological feature of immunoglobulin A nephropathy (IgAN), an autoimmune kidney disease, is the deposition of IgA immune complexes, accompanied by mesangial cell proliferation and elevated urine protein. The Guben Tongluo formula (GTF) is a traditional Chinese medicine prescription, which has predominant protective effects on IgAN. However, the therapeutic mechanism of the GTF in IgAN remains elusive. The present study aimed to determine the effects of GTF in treating IgAN via regulating the TLR4/MyD88/NF-κB pathway. METHODS: In the present study, lamina propria B lymphocytes were treated with different concentrations of lipopolysaccharide (LPS) (0, 1, 5, 10 and 20 ng/mL). Flow cytometry was used to define positive CD86+CD19+ cells. CCK-8 assay was used to examine cell proliferation. RNAi was used to induce TLR4 silencing. qRT-PCR and Western blotting were used to determine gene expression. RESULTS: It was found that the LPS dose-dependently increased the content of IgA and galactose-deficient IgA1 (Gd-IgA), the levels of TLR4, Cosmc, MyD88 and phosphorylated (p)-NF-κB, and the ratio of CD86+CD19+ and IgA-producing B cells. However, the TLR4 knockdown reversed the role of LPS. This suggests that TLR4 mediates the effects of LPS on lamina propria B lymphocytes. Furthermore, the GTF could dose-dependently counteract the effects of LPS and TLR4 overexpression on lamina propria B lymphocytes through the TLR4/MyD88/NF-κB pathway. CONCLUSION: Collectively, these results demonstrate that the GTF can regulate the TLR4/MyD88/NF-κB pathway to treat IgAN model lamina propria B lymphocytes stimulated by LPS.

Prophylactic Protective Action of Aqueous Extract of Green Oak Acorns on Ethanol-Induced Acute Injury to Rat Gastroduodenal Mucosa.

Quercus ilex fruit is widely used in the treatment of various gastrointestinal disorders, including diarrhea, for its bioactive compounds and astringent property. The current study focuses on the phytochemical characterization of the Q. ilex-aqueous extract (QIAE) and its protective effect against gastroduodenal (GD) ulcer (GDU) produced by absolute ethanol (EtOH) intoxication in adult male Wistar rats. Experimental rats were divided into six groups (n = 6): control, EtOH [95%, 4 g/kg body weight (b.w.)], EtOH + different doses of QIAE (100, 200, and 400 mg/kg, b.w.), and EtOH + Famotidine (FAM, 10 mg/kg, b.w.). Animals were orally pretreated (p.o.) with QIAE for 15 days and intoxicated with a single oral administration of EtOH for 2 h. The findings showed that the QIAE is rich in phenolic-astringent compounds and fibers, and it exhibited a significant scavenging activity on DPPH/ABTS free-radicals with half maximal inhibitory concentration (IC50) values of 177.00 ± 5.11 and 203.9 ± 2.23 µg/mL, respectively. In vivo part, QIAE significantly reduced the GD mucosal injury revealed by edema and leukocyte infiltration of the submucosal layer. GD mucosal homogenates revealed a remarkable increase in endogenous antioxidant enzyme activities (catalase, superoxide dismutase, and glutathione peroxidase) and a decrease in the lipid peroxidation levels (malondialdehyde) in animals pretreated with QIAE compared with the ulcer control group. QIAE exerted significant and dose-dependent anti-GDU protection in the rat model with a more effective action than FAM. The GD protective effect of the QIAE might be related to a direct radical scavenging activity, increased antioxidant enzymes, and depression of lipid peroxidation.

The possible protective role of N-acetyl cysteine on duodenal mucosa of high fat diet and orlistat treated adult male albino rats and the active role of tumor necrosis factor α (TNFα) and Interleukin 6 (IL6) (histological and biochemical study).

BACKGROUND: Obesity is a major universal health issue linked to a majority of illness. AIM: To evaluate the histological and biochemical changes occurred in the duodenal mucosa of high fat diet HFD and orlistat fed rats and to assess the possible protective role of N-acetyl cysteine NAC supplementation. MATERIAL AND METHOD: Sixty male albino rats weighing 180-200 g were classified randomly into control group I and three experimental groups (HFD group II, HFD + orlistat group III, and HFD + orlistat + NAC group IV). All experimental groups received HFD alone/and treatment for 6 weeks. Group III received orlistat (32 mg/kg/day) before meals and group IV received the same regimen as group III in addition to NAC (230 mg/kg/day) after meals. After completion of the experiment, duodenal sections were processed for histological examination, oxidative stress parameters, and semiqualitative real time PCR for proinflammatory mediators TNFα and IL6 evaluation. Also, plasma lipid parameters were assessed and morphometric duodenal results were analyzed statistically. RESULTS: By histological examination of HFD and (HFD + orlistat) groups, we found severe to moderate duodenal structural disturbances, increased goblet cells, collagen fibers, and BAX and iNOS immunostaining. By Biochemical examination, both groups showed increased proinflammatory markers level (TNFα and IL6) with decreased all antioxidant parameters and increased MDA. Moreover, NAC treatment in group IV significantly reduced all structural changes, levels of proinflammatory mediators and increased all antioxidant parameter levels and decreased MDA. CONCLUSION: All findings elucidated that NAC could be accounted to be a useful drug for protection of duodenal mucosa of HFD and orlistat treated animals.

Extracts of Poria cocos improve functional dyspepsia via regulating brain-gut peptides, immunity and repairing of gastrointestinal mucosa.

BACKGROUND: Poria cocos (Schw.) Wolf (PC), a fungus, has been used for more than 2000 years as a food and medicine in China. It has a very good therapeutic effect for functional dyspepsia (FD). However, the material basis and mechanism of PC on FD were not reported. PURPOSE: To investigate the function and potential mechanisms of PC including its three extracts (triterpenoid, PCT; water-soluble polysaccharide, PCWP; acidic polysaccharide, PCAP) on FD. STUDY DESIGN: The study explored the therapeutic effect of PC and its three extracts on FD in rats for the first time and discussed its mechanisms based on brain-gut peptides, immunity and repair of the gastrointestinal mucosa. METHODS: The chemical components of PC extracts were analyzed and quantified using ultra high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) and gel permeation chromatography coupled with size exclusion chromatography (GPC/SEC). The FD rat models were established using weight-loaded forced swimming and alternate-day fasting for 42 days. After 14 days of treatment, the effect and mechanisms were investigated using ELISA, histopathology, immunohistochemistry as well as Western blot. RESULTS: Seventy-seven triterpenoids in PCT were identified. PCWP was primarily composed of component A (Mw: 3.831 × 107 Da), component B (Mw: 5.650 × 106 Da) and component C (Mw: 113,117 Da). PCAP was a homogeneous composition with an average Mw of 74,320 Da. PCT, PCWP and PCAP alleviated the symptoms of FD. These extracts promoted the repair of gastrointestinal mucosa and regulated the balance between the T helper cell (Th)1/Th2 axis and the Th17/Treg axis. PCT and PCWP regulated brain-gut peptides more effectively, PCWP and PCAP enhanced immunity more effectively. Further study demonstrated that these extracts may have enhanced immunity via the Toll-like receptor (TLR) and c-Jun N-terminal kinase (JNK) signaling pathways. CONCLUSIONS: PC extracts showed therapeutic effects on FD rats, and the mechanism of action involved multiple pathways. PCAP, which is often discarded in traditional applications, was effective. Our study provides new ideas for the application and development of PC extracts.

Comparison of Biological Characteristics of Different Paranasal Sinus Mucosa in Goats.

BACKGROUND/PURPOSE: Prosthetic implants are the primary treatment for patients with edentulism. This study aims to explore and compare the biological characteristics of mucosal thickness and tensile strength of the paranasal sinuses (maxillary and frontal sinuses) in goats, thereby providing a theoretical basis and guidance for mucosa-related problems involved in maxillary sinus lifting. MATERIALS AND METHODS: The paranasal sinus mucosa (maxillary sinus crest, maxillary sinus floor and frontal sinus mucosa) was obtained from the goats for use in maxillary sinus lifting. The mucosa was made into tissue section specimens and evaluated by a computer with built-in screenshot software and an optical microscope with a graduated eyepiece. A total of 3 readings were randomly selected and recorded. The mucosa was clamped with a laboratory-made clamp device. After connecting the push-pull meter, the mucosa exposed by the inner ring of the clamp device was pressed vertically and uniformly until it ruptured. The strength value was read and recorded. The left and right ends of the mucosa were connected with the clamp device; horizontal tension was applied evenly to the mucosa until the mucosa ruptured. The strength value was read and recorded. The normality test, analysis of variance, LSD pairwise comparison and linear regression were performed for each group of data. RESULTS: The thicknesses of the maxillary sinus crest mucosa, floor mucosa and frontal sinus mucosa in goats were 410.03 ± 65.97 um, 461.33 ± 91.37 um and 216.90 ± 46.47 um, respectively. There were significant differences between the maxillary sinus crest and frontal sinus and the maxillary sinus floor and frontal sinus (P < .05). The range of tensile strength of the maxillary sinus crest mucosa, floor mucosa and frontal sinus mucosa in goats was 0.48 ± 0.10 kg, 0.54 ± 0.11kg and 0.20 ± 0.05kg, respectively. There were significant differences between the maxillary sinus crest and frontal sinus and the maxillary sinus floor and frontal sinus (P < .05). Tensile strength was positively correlated with the thickness of the mucosa of the maxillary and frontal sinuses (P < .05). CONCLUSION: The mucosal thickness and tensile strength of the maxillary sinus crest and floor were greater than those of the frontal sinus mucosa. There was a positive correlation between the tensile strength and the thickness of the mucosa.