The roles and potential mechanisms of plant polysaccharides in liver diseases: a review.

Plant polysaccharides (PP) demonstrate a diverse array of biological and pharmacological properties. This comprehensive review aims to compile and present the multifaceted roles and underlying mechanisms of plant polysaccharides in various liver diseases. These diseases include non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), fibrosis, drug-induced liver injury (DILI), and hepatocellular carcinoma (HCC). This study aims to elucidate the intricate mechanisms and therapeutic potential of plant polysaccharides, shedding light on their significance and potential applications in the management and potential prevention of these liver conditions. An exhaustive literature search was conducted for this study, utilizing prominent databases such as PubMed, Web of Science, and CNKI. The search criteria focused on the formula "(plant polysaccharides liver disease) NOT (review)" was employed to ensure the inclusion of original research articles up to the year 2023. Relevant literature was extracted and analyzed from these databases. Plant polysaccharides exhibit promising pharmacological properties, particularly in the regulation of glucose and lipid metabolism and their anti-inflammatory and immunomodulatory effects. The ongoing progress of studies on the molecular mechanisms associated with polysaccharides will offer novel therapeutic strategies for the treatment of chronic liver diseases (CLDs).

Tissue re-distribution of budesonide in rats co-administrated with curcumin by ultra performance liquid chromatography-tandem mass spectrometry.

Budesonide (BUD), a locally acting glucocorticoid with low side effects, is recommended in several Crohn's disease (CD) drug treatment guidelines as the first choice for early treatment. Nevertheless, the extensive first-pass effect mediated by P-glycoprotein (P-gp) and Cytochrome P450 3A4 (CYP3A4) leads to low bioavailability and limits further applications. Curcumin (CUR), a natural polyphenol derived from turmeric, has been found to influence the in vivo processes of drugs by affecting the activity of P-gp and CYP3A4. However, the pharmacokinetic interactions between BUD and CUR remains elusive, so an ultra high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for the simultaneous determination of BUD and CUR in the tissue. The results showed that the area under the concentration-time curve 0 to time (AUC0→t) of BUD in the colon and kidney increased by approximately 32.35% and 39.03% respectively in the co-administered group compared to the single-drug group, while the small intestine, liver and plasma decreased by 80.03%, 67.34% and 24.34% respectively compared to the single-drug group. Therefore, long-term treatment with CUR can increase the concentration of BUD in the colonic area without increasing its systemic exposure, thus potentially reducing the incidence of side effects.

Pharmacokinetic and safety profile of PT109B, a novel multi-targeted compound against Alzheimer's disease.

PT109B, 5-(1,2-dithiolan-3-yl)-N-((1r,4r)-4-(isoquinolin-5-ylamino) cyclohexyl) pentanamide, a novel compound structurally related to Fasudil, has been reported as a promising candidate for treating Alzheimer's disease. To investigate the pharmacokinetics and acute toxicity of PT109B in rodents, we first developed and validated a UPLC-MS/MS analytical method to detect PT109B concentration in the biological matrix. The proposed method could separate and quantify the PT109B with good precision and accuracy. The pharmacokinetic results showed that the concentrations of PT109B in rat plasma increased with the dose, but not proportionally. Meanwhile, the double-peak phenomenon disappeared when decreasing the oral administration dosage. In addition, we found that PT109B could be detected in the central nervous system, and highly distributed in the liver and kidney. At the same time, the gender difference of PT109B in rats was observed, and the exposure of PT109B in female rats was significantly higher than that in male rats after oral administration. Finally, we found that oral administration of 750 mg/kg PT109B to C57 BL/6 mice caused significant liver injury in females, which was specifically manifested as hepatomegaly, increased liver coefficient, and hepatocyte ballooning. However, no significant damage was observed in other organs, which may be related to the distribution of PT109B in the liver. In summary, we first established a UPLC-MS/MS method for the analysis of PT109B in a biological matrix and described the characteristics of pharmacokinetics, and acute toxicity of PT109B in rodents, providing a sufficient pharmacokinetic basis for further study of PT109B.

Machine learning approach identified clusters for patients with low cardiac output syndrome and outcomes after cardiac surgery.

Background: Low cardiac output syndrome (LCOS) is the most serious physiological abnormality with high mortality for patients after cardiac surgery. This study aimed to explore the multidimensional data of clinical features and outcomes to provide individualized care for patients with LCOS. Methods: The electronic medical information of the intensive care units (ICUs) was extracted from a tertiary hospital in South China. We included patients who were diagnosed with LCOS in the ICU database. We used the consensus clustering approach based on patient characteristics, laboratory data, and vital signs to identify LCOS subgroups. The consensus clustering method involves subsampling from a set of items, such as microarrays, and determines to cluster of specified cluster counts (k). The primary clinical outcome was in-hospital mortality and was compared between the clusters. Results: A total of 1,205 patients were included and divided into three clusters. Cluster 1 (n = 443) was defined as the low-risk group [in-hospital mortality =10.1%, odds ratio (OR) = 1]. Cluster 2 (n = 396) was defined as the medium-risk group [in-hospital mortality =25.0%, OR = 2.96 (95% CI = 1.97-4.46)]. Cluster 3 (n = 366) was defined as the high-risk group [in-hospital mortality =39.2%, OR = 5.75 (95% CI = 3.9-8.5)]. Conclusion: Patients with LCOS after cardiac surgery could be divided into three clusters and had different outcomes.

Analysing use of the Chinese HHIE-S for hearing screening of elderly in a northeastern industrial area of China.

OBJECTIVE: The aim of the present study was to investigate the use of Chinese version of HHIE-S as a hearing screening tool for the elderly in an industrial area in northeast China. DESIGN: Prevalence, sensitivity and specificity of Chinese version of HHIE-S were calculated. Factors that had impact on HHIE-S were analysed. STUDY SAMPLE: Five hundred and seventy Mandarin speaking participants, aged from 50 to 85 years were included. They were tested with pure tone audiometry and Chinese version of HHIE-S. RESULTS: The prevalence of hearing handicap was 55.3%. The sensitivity and specificity of HHIE-S were 84.5% and 58.3% respectively when the pass/fail criteria were set at PTA0.5-4kHz >40 dBHL. In general, HHIE-S total and subscale scores were significantly associated with severity of hearing impairment. After stratified by severity of hearing impairment, both the prevalence of reported handicap and the scores of HHIE-S were not significantly associated with age. Male participants had significantly higher HHIE-S scores than female participants did. CONCLUSIONS: The Chinese version of HHIE-S contributes useful information to identifying hearing handicap and addressing the rehabilitative needs in the elderly in an industrial city in Mainland China.

Enhanced growth suppression of TERT-positive tumor cells by oncolytic adenovirus armed with CCL20 and CD40L.

Conditionally replicating adenoviruses (CRAds) selectively replicate in cancer cells and induce cell lysis, which represents a potential platform for cancer immunotherapy. The chemokine CCL20 exerts antitumor activity via chemoattraction of immature dendritic cells (DCs) and lymphocytes. However, the activation and maturation status of DCs is a limiting factor in the DCs -based immunity response. CD40L induces the phenotypic maturation of DCs, mediates DCs cytokine secretion, and increases the expression of FasL, which mediates apoptosis. We constructed a CCL20/CD40L co-expression CRAds (Ad-CCL20-CD40L) based on the AdEasy system. Ad-CCL20-CD40L was constructed from three plasmids, pGTE-CD40L, pShuttle-CMV-CCL20 and AdEasy-1, and was homologously recombined and propagated in the Escherichia coli strain BJ5183 and the packaging cell line HEK-293, respectively. Ad-CCL20-CD40L selectively replicates in TERT-positive tumor cells because the pGTE-CD40L plasmid contains the telomerase reverse transcriptase promoter (TERTp). Our results showed that Ad-CCL20-CD40L induced oncolytic effects and tumor-specific cytotoxicity of cytotoxic T lymphocytes (CTLs) in vitro. This study suggests that Ad-CCL20-CD40L can induce the antitumor immune response and that this platform can be modified to generate novel CRAds with other transgenes.

Streptozotocin Aggravated Osteopathology and Insulin Induced Osteogenesis Through Co-treatment with Fluoride.

The role of insulin in the mechanism underlying the excessive fluoride that causes skeletal lesion was studied. The in vitro bone marrow stem cells (BMSC) collected from Kunming mice were exposed to varying concentrations of fluoride with or without insulin. The cell viability and early differentiation of BMSC co-treated with fluoride and insulin were measured by using cell counting kit-8 and Gomori modified calcium-cobalt method, respectively. We further investigated the in vivo effects of varying dose of fluoride on rats co-treated with streptozotocin (STZ). Wistar rats were divided into six groups which included normal control, 10 mg fluoride/kg day group, 20 mg fluoride/kg day group, STZ control, STZ+10 mg fluoride/kg day group, and STZ+20 mg fluoride/kg day group. The rats were administered with sodium fluoride (NaF) by gavage with water at doses 10 and 20 mg fluoride/kg day for 2 months. In a period of one month, half of rats in every group were treated with streptozotocin (STZ) once through intraperitoneal injection at 52 mg/kg body weight. The serum glucose, HbA1c, and insulin were determined. Bone mineral content and insulin release were assessed. The results showed insulin combined with fluoride stimulated BMSC cell viability in vitro. The bone mineral content reduced in rats treated with higher dose of fluoride and decreased immensely in rat co-treated with fluoride and STZ. Similarly, a combination treatment of a high dose of fluoride and STZ decreased insulin sensitivity and activity. To sum up, these data indicated fluoride influenced insulin release, activity, and sensitivity. Furthermore, the insulin state in vivo interfered in the osteogenesis in turn and implied there was a close relation between insulin and bone pathogenesis in the mechanism of fluoride toxicity.

Enhanced antitumor immunity is elicited by adenovirus-mediated gene transfer of CCL21 and IL-15 in murine colon carcinomas.

The chemokine CCL21 is a potent chemoattractant for T cells and dendritic cells. IL-15 elicits powerful antitumor immune responses through the stimulation of natural killer cells. We constructed a CCL21/IL-15-expressing adenovirus (Ad-CCL21-IL-15) and evaluated its antitumor effects in vitro and in vivo. We found that the intratumoral injection of Ad-CCL21-IL-15 into murine colon carcinomas significantly inhibited tumor growth. Splenocytes from mice treated with Ad-CCL21-IL-15 developed tumor-specific cytotoxic T cells and were protected from subsequent challenges with tumor cells. This study indicates that providing cancer therapy by combining CCL21 and IL-15 can induce antitumor immune responses and is an effective strategy for cancer immunotherapy.

Adenovirus-mediated CCL20/IL-15 gene transfer enhances antitumor immunity in mice.

The CCL20 chemokine has potent antitumor activities through chemoattracting immature dentritic cells. But the maturation status of tumoral dentritic cells is important limiting factors in DC-based immunity. The endogenous availability of IL-15 was effective in inducing the dentritic cells maturation and IL-15 also shows tumor-specific antitumor activities. We constructed a CCL20/IL-15 bicistronic adenovirus (Ad-CCL20-IL-15) and confirmed its combined antitumor effect in vitro and in vivo. Intratumoral injection of Ad-CCL20-IL-15 into both CT-26 and B16F10 cells resulted in marked reduction of tumor growth in our model. Splenocytes treated by Ad-CCL20-IL-15 developed tumor-specific cytotoxic T cells and IFN-γ secretion could protect mice from rechallenging. This study suggests that CCL20/IL-15 can induce a strong antitumor immune response in tumor tissues and it is a suitable candidate for cancer immunotherapy.

[ShRNA-mediated silencing of MDM2 inhibits growth of HepG2 hepatocellular carcinoma cells xenografted in nude mice].

OBJECTIVE: To construct a short hairpin (sh)RNA targeting the gene encoding the MDM2 oncoprotein in order to investigate its role in human hepatocellular carcinoma (HCC) and its potential for use as a gene therapy strategy to inhibit HCC growth in vivo. METHODS: Small interfering (si)RNAs were designed targeting the MDM2 gene (siMDM2-1 and siMDM2-2) and unrelated sequences (negative control) and cloned into the expression plasmid pGCSilencer-U6-neo-GFP. A HCC mouse model was established by subcutaneous inoculation of HepG2 cells (2 x 10(6) in 0.2 ml) into 20 nude mice. The inoculated mice were divided into four equal groups for tumor-localized injections of saline, negative control siRNA plasmid, siMDM2-1 plasmid, and siMDM2-2 plasmid. Tumor growth was observed daily (by caliper measurement) for one month, when mice were sacrificed by cervical dislocation. The tumor mass was resected for analysis of tumor inhibition rate (% = [(average tumor weight of control group - average tumor weight of treatment group) / average tumor weight of control group x 100]) and effects on MDM2 and p53 mRNA and protein expression (by reverse transcription- PCR and western blotting, both normalized to beta-actin). Significance of between-group differences was assessed by one-way ANOVA or LSD test; pairwise comparisons were made by the Chi-squared test. RESULTS: siMDM2-1 and siMDM2-2 suppressed the xenografted tumor growth remarkably (60.6% and 54.6% inhibition rates, respectively), significantly reduced the expression ofMDM2 gene (62.8% and 61.6%) and protein (60.7% and 59.5%), and significantly increased p53 gene (47.1% and 45.6%) and protein (45.9% and 44.3%) (all, P < 0.05). CONCLUSION: shRNA-mediated silencing of the MDM2 gene effectively inhibits HCC tumorigenesis of subcutaneously xenografted HepG2 cells in nude mice, and the mechanism may involve p53.

Staphylococcus aureus infection of intestinal epithelial cells induces human umbilical cord-derived mesenchymal stem cell migration.

There is a growing interest in umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) for cellular therapy in regenerative medicine. To aid in tissue repair, MSCs are recruited to sites of inflammation induced by a bacterial infection. The primary objective of this study was to explore the mechanisms of MSC recruitment to intestinal epithelial cells infected with Staphylococcus aureus. First, we isolated and characterized the UCB-derived MSCs used in our experiments. Next, we determined the ability of S. aureus infected intestinal epithelial cells to induce migration of UCB-derived MSCs. Expression analysis of cytokines secreted by infected epithelial cells indicated that MSC migration occurred predominately via a nuclear factor-kappa B (NF-κB)-dependent signaling pathway. Altogether, our data provide the first evidence for a role of S. aureus infection in MSC migration and reveal the function of UCB-derived MSCs in intestinal pathophysiology.

Identification and characterization of antigenic epitope of Staphylococcus aureus ClfA adhesin.

Staphylococcus aureus ClfA adhesin is a protective antigen that induces partial immunity against S. aureus infection in mice. To identify the antigenic epitope of ClfA, a monoclonal antibody (mAb) D01 against the recombinant protein was produced by the hybridoma technique. The mAb was used to immunoscreen a random phage-displayed peptide library as the immunogen. After three rounds of biopanning, 41 positive clones were identified. Sixteen phage clones were sequenced and their amino acids were deduced. One mimotope (SKVGIDKRRGTA) showed good match with ClfA adhesin at 383-394 aa and the serum of mice induced by the phage clone clearly recognized ClfA adhesin.

Identification of Th cell epitopes on clfA adhesin of Staphylococcus aureus and characterization of their role in immunity.

OBJECTIVE: The ClfA adhesin of Staphylococcus aureus is an excellent vaccine candidate antigen. CD4 + T cells play central roles during immune responses, but their functional contributions to Staphylococcus aureus in fection have yet to be evaluated. METHODS: By using the SYFPEITHI prediction algorithm, we identified and characterized four Th epitopes within the ClfA adhesin. RESULTS: Peptide C335 was I-Ed restricted Th1 type epitopes; peptides C214, C286, and C436 were I-Ad restricted Th2 type epitope. CONCLUSION: The identification of these epitopes is important to evaluate and optimize the vaccine-primed protection against Staphylococcus aureus infection.

Randomized controlled trial of the intraoperative bile leakage test in preventing bile leakage after hepatic resection.

AIM: To evaluate the value of an intraoperative bile leakage test during liver resection in preventing bile leakage after hepatic resection. METHODS: A sterile fat emulsion was injected through the duct of the gallbladder among patients from the treatment group so as to observe leakage status on the hepatic resection plane; the leakage points were dealt with in time. The hepatic resection plane was treated using conventional methods among patients from the control group. RESULTS: The incidence rates of the bile leakage and other complications in the two groups were analyzed in this study. Two (3.7%) of the 53 patients from the treatment group had bile leakage, and 8 (14.8%) of the 54 patients from the control group had bile leakage. There were significant differences between the two groups (p < 0.05) in terms of the incidence of the bile leakage. With regard to the incidence of other complications, there were no significant differences between the two groups (p > 0.05). CONCLUSIONS: An intraoperative bile leakage test appears to be sensitive in detecting interoperative bile leaks and can effectively prevent bile leakage after hepatic resection, and it does not increase the likelihood of other complications.

Proteomic alteration of Marc-145 cells and PAMs after infection by porcine reproductive and respiratory syndrome virus.

Viral infections usually result in alterations in the host cell proteome, which determine the fate of infected cells and the progress of pathogenesis. To uncover cellular protein responses in porcine reproductive and respiratory syndrome virus (PRRSV), infected pulmonary alveolar macrophages (PAMs) and Marc-145 cells were subjected to proteomic analysis involving two-dimensional electrophoresis (2-DE) followed by MALDI-TOF-MS/MS identification. Altered expression of 44 protein spots in infected cells was identified in 2D gels, of which the 29 characterised by MALDI-TOF-MS/MS included 17 up-regulated and 12 down-regulated proteins. Some of these proteins were further confirmed at the mRNA level using real-time RT-PCR. Moreover, Western blot analysis confirmed the up-regulation of HSP27, vimentin and the down-regulation of galectin-1. Our study is the first attempt to analyze the cellular protein profile of PRRSV-infected Marc-145 cells using proteomics to provide valuable information about the effects of PRRSV-induced alterations on Marc-145 cell function. Further study of the affected proteins may facilitate our understanding of the mechanisms of PRRSV infection and pathogenesis.

Using CT imaging to delineate the prostatic apex for radiation treatment planning.

BACKGROUND AND OBJECTIVE: In computed tomography (CT)-based radiotherapy planning for prostate cancer, it is difficult to precisely delineate the prostatic apex because of its relationship with the urogenital diaphragm and bulbospongiosus musculature. In this retrospective study, we analyzed the magnetic resonance imaging (MRI) and CT scans of the patients with prostate cancer to investigate the relationship between the prostatic apex and the anatomic structure visible on CT, and to provide evidence for localizing the prostatic apex in radiotherapy planning. METHODS: MRI and CT scans of 108 patients with prostate cancer were analyzed to measure the distances between the prostatic apex and the bottom of ischial tuberosities, the bottom of obturator foramen, the bottom of pubic symphysis, and the bulb of the penis. The volume of the prostate was measured to analyze its relationship with the localization of the prostatic apex. RESULTS: The prostatic apex was located (13.1±3.3) mm above the bulb of the penis, (11.0±5.4) mm above the bottom of the obturator foramen, (31.3±5.5) mm above the ischial tuberosities, and (7.1±4.7) mm above the bottom of the symphysis pubis. There was no correlation between the size of the prostate and the localization of the prostatic apex. CONCLUSIONS: The variance of the distance between the prostatic apex and the bulb of the penis is smaller than that of the distance between the apex and bony anatomy. Delineating the target to 6 mm above the bulb of the penis can cover the prostatic apex in 95% of the patients with prostate cancer, delineating to the bottom of obturator foramen can cover the prostatic apex in 100% of the patients.