Colon-targeted delivery of polyphenols: construction principles, targeting mechanisms and evaluation methods.

Polyphenols have received considerable attention for their promotive effects on colonic health. However, polyphenols are mostly sensitive to harsh gastrointestinal environments, thus, must be protected. It is necessary to design and develop a colon-targeted delivery system to improve the stability, colon-targeting and bioavailability of polyphenols. This paper mainly introduces research on colon-targeted controlled release of polyphenols. The physiological features affecting the dissolution, release and absorption of polyphenol-loaded delivery systems in the colon are first discussed. Simultaneously, the types of colon-targeted carriers with different release mechanisms are described, and colon-targeting assessment models that have been studied so far and their advantages and limitations are summarized. Based on the current research on polyphenols colon-targeting, outlook and reflections are proposed, with the goal of inspiring strategic development of new colon-targeted therapeutics to ensure that the polyphenols reach the colon with complete bioactivity.

Health benefits of anthocyanin-containing foods, beverages, and supplements have unpredictable relation to gastrointestinal microbiota: A systematic review and meta-analysis of random clinical trials.

Anthocyanins are a type of natural pigment that has numerous health benefits. In recent years, the interaction of anthocyanins with gastrointestinal (GI) microbiota has been presented as a viable paradigm for explaining anthocyanin activities. The current study performed a systematic review and meta-analysis to determine the potential modulation of GI microbiota by anthocyanins in human health improvement. Clinical trials were retrieved from PubMed, Cochrane, Web of Knowledge, China Biology Medicine, China National Knowledge Infrastructure, and ClinicalTrials.gov with no language restrictions. Eight clinical trials (252 participants) were selected from the 1121 identified studies and the relative phylum abundance extracted from the trials was analyzed using a random-effects model. Based on the analysis, anthocyanins had no effect on the relative abundance of Firmicutes (standard mean difference [SMD]: -0.46 [-1.25 to 0.34], P = .26), Proteobacteria (SMD, -0.32 [-0.73 to 0.09], P = .13), nor Actinobacteria (SMD, -0.19 [-0.50 to 0.12], P = 0.24), but influenced the abundance of Bacteroidetes (SMD, 0.84 [0.17 to 1.52], P = .01) when compared with placebo/control. No significant influence on the relative abundance was detected when the data were analyzed following the "posttreatment vs. pretreatment" strategy. Our preliminary analysis revealed that the effects of anthocyanins on human GI microbiota vary between studies and individuals, and at the current stage, the clinical trials regarding the effects of anthocyanin interventions on human GI microbiota are lacking. More trials with larger sample sizes are needed to promote the clinical application of anthocyanins.

Mechanism of sugar degradation product 5-hydroxymethylfurfural reducing the stability of anthocyanins.

The coexistence of anthocyanin with the sugar degradation product 5-hydroxymethylfurfural (5-HMF) is inevitable during the processing and storage of anthocyanin-rich juices. It was determined from our study that lower concentrations of 5-HMF have little effect on the stability of Cyanidin-3-O-glucoside (C3G), and even cause a slight increase for a short period of time. As the concentration of 5-HMF increased, the retention of C3G decreased and the color of the solution changed from orange-red to purple-red. The reaction sites of 5-HMF and C3G in its hemiketal form were predicted by quantum chemical calculations in order to investigate the pathways of action of the two. The degradation mechanism of 5-HMF on anthocyanin was verified by Ultraviolet and Visible spectrophotometer and Ultra performance liquid chromatography-mass spectrometry. Therefore, this article provides further theoretical support for the study of the effect of furfural compounds, which are sugar degradation products, on the stability of anthocyanins.

Comparative study on alleviating effect of kiwi berry (Actinidia arguta) polysaccharide and polyphenol extracts on constipated mice.

Kiwi berry (Actinidia arguta) is beneficial for relieving constipation, but the mechanism of easing constipation is still unknown. The alleviating effects of kiwi berry polysaccharide and polyphenol extracts on loperamide induced constipation were studied. Administration with polysaccharide extract of kiwi berry in loperamide-induced constipation mice distinctly decreased the body weight gain by 124.0%, the number and the water content of feces was decreased by 152.4% and 107.0% respectively, gastrointestinal (GI) transit rate was decreased by 39.5% and the time to the first dark stool was largen by 56.2% as compared with those in the loperamide group, respectively. The levels of excitability neurotransmitters were increased, and the inhibitory neurotransmitter was decreased in the kiwi berry extracts groups compared with the loperamide group. The levels of aquaporins were decreased to ameliorate constipation. Moreover, kiwi berry extracts can protect colon smooth muscle cells from apoptosis and help to restore colon health. Interstitial cells of Cajal (ICC) and animal experiments suggested that kiwi berry extracts can up-regulate the expression levels of stem cell factors (SCF)/c-kit protein. Kiwi berry can remodel the structure of microbial communities. All findings suggest that kiwi berry polysaccharide and polyphenol especially its polysaccharide extract, can effectively alleviate constipation induced by loperamide. Kiwi berry is a promising food supplement that can be used to relieve constipation.

Complete mitochondrial genome of Cultellus attenuatus and its phylogenetic implications.

BACKGROUND: The mitochondrial genomes of three species in Solenoidea of Heterodonta have been reported, but the mitochondrial genes and phylogenetic relationships of Cultellus attenuatus, which also belongs to this superfamily and has high economic value, are unknown. METHODS AND RESULTS: The complete mitochondrial genome of C. attenuatus was sequenced and compared with mitogenomes of seven species of Heterodonta bivalve mollusks in GenBank. The mitochondrial genome of C. attenuatus has a length of 16,888 bp and contains 36 genes, including 12 protein-coding genes, 2 ribosomal RNAs and 22 transfer RNAs. In comparison with C. attenuates, the mitochondrial genes of Sinonovacula constricta from the same family were not rearranged, but those of six other species from different families were rearranged to different degrees. The location, size, and composition of the largest noncoding regions in eight species suggested a closer relationship between C. attenuatus and S. constricta. The phylogenetic analysis showed that C. attenuatus and S. constricta belonging to Cultellidae cluster into one branch and that two species of Solenidae (Solen grandis and Solen strictus) clustered as their sister taxa. CONCLUSIONS: Overall, we used mitochondrial genome data to demonstrate that C. attenuatus and S. constricta exhibit the closest relationship in Heterodonta. These data and analyses provide new insights into the phylogenetic relationships in Heterodonta.

Clinical analysis of transurethral holmium laser enucleation in the treatment of benign prostatic hyperplasia with prostatic inflammation: A prospective research study.

Objective: To investigate the clinical efficacy of holmium laser enucleation of the prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH) with prostatic inflammation (PI). Methods: We prospectively collected and followed up data on patients with BPH who underwent HoLEP at the Affiliated Hospital of Weifang Medical University between July 2021 and July 2022. According to the postoperative pathological results, the patients were divided into two groups: BPH without PI group (BPH group) and BPH with PI group. Statistical analysis was performed on clinical data, including age and body mass index (BMI), prostate volume (PV), postoperative residual urine volume (PVR), preoperative serum total prostate-specific antigen (tPSA), serum-free prostate-specific antigen (fPSA), preoperative and postoperative maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS) before and 3 months after surgery, quality of life index (QoL) before and 3 months after surgery, and postoperative complications. Results: A total of 41 patients were included in this study, including 16 in the BPH group and 25 in the BPH with PI group. There were no significant differences in preoperative age, BMI, PV, PVR, tPSA, fPSA, and f/tPSA between the BPH and BPH with PI groups (P > 0.05). The preoperative mean Qmax of the BPH and BPH with PI groups were 9.44 ± 2.449 and 7.52 ± 2.946 [mean ± standard deviation (SD)] ml/s, mean IPSS were 17.75 ± 5.335 and 24.24 ± 5.861 (mean ± SD), and mean QoL were 4.13 ± 0.806 and 4.48 ± 0.8 (mean ± SD), respectively. The postoperative mean Qmax of the BPH and BPH with PI groups were 20.38 ± 4.787 and 14.32 ± 3.827 (mean ± SD) ml/s, mean IPSS were 2.69 ± 1.25 and 5.84 ± 3.579 (mean ± SD), and mean QoL were 0.13 ± 0.342 and 0.92 ± 0.759 (mean ± SD), respectively. In both groups, Qmax significantly increased (P < 0.05) and IPSS and QoL significantly decreased after HoLEP (P < 0.05). Before and after surgery, the Qmax in the BPH with PI group was lower than that in the BPH group, and the IPSS and QoL levels in the BPH with PI group were higher than those in the BPH group (P < 0.05). Compared with the BPH group, the increase in Qmax in the BPH with PI group was smaller and the decrease in IPSS was larger (P < 0.05), but the variation in QoL was not statistically significant (P > 0.05). Conclusion: Improvements in Qmax, IPSS, and QoL in BPH patients with PI after HoLEP surgery were lower than those in BPH patients alone. PI may be a predictor of a worse response to surgical treatment. However, more multicenter randomized controlled trials with larger samples and long-term follow-up are needed to verify this.

High glucose inhibits apoptosis induced by serum deprivation in vascular smooth muscle cells via upregulation of Bcl-2 and Bcl-xl.

Apoptosis plays a critical role in normal vascular development and atherosclerosis. To test the hypothesis that diabetic vasculopathy may be due in part to altered apoptosis pathways, we investigated the effects of high glucose treatment on serum withdrawal-induced apoptosis, expression of Bcl-2 family members, and inhibitor of apoptosis protein (IAP)-1 in vascular smooth muscle cells (VSMCs). Treatment with a high concentration of glucose (22 mmol/l) significantly attenuated apoptosis in response to serum withdrawal in cultured rat VSMCs compared with cells treated with a normal glucose concentration (5.5 mmol/l). This attenuation was accompanied by a significant decrease in the caspase-3 activity in comparison with the normal glucose group. Furthermore, exposure of VSMCs to high glucose markedly increased the abundance of Bcl-2 and Bcl-xl mRNAs compared with treatment with normal glucose, while expression of bax and IAP-1 mRNA remained unchanged. Our results suggest that high glucose suppresses serum withdrawal-induced apoptosis in VSMCs by upregulating expression of Bcl-2 and Bcl-xl, suggesting that enhanced expression of antiapoptotic proteins may play an important role in the development of macrovascular complications in diabetes.

Effects of C-peptide on expression of eNOS and iNOS in human cavernosal smooth muscle cells.

OBJECTIVES: To investigate the role of C-peptide alone or in conjunction with insulin on the expression of nitric oxide synthase (NOS) in human corpus cavernosum smooth muscle cells (HCSMCs). Erectile dysfunction, among diabetic patients, is a significant health problem. The specific causes of erectile dysfunction are unknown. It has been suggested that impairment of penile relaxation is related to a reduction of penile NOS. Plasma levels of C-peptide and insulin are decreased in individuals with type 1 diabetes and late-stage type 2 diabetes. METHODS: Primary cultures were initiated from explants of HCSMCs. Confluent cells at passages 2 to 4 were assigned to one of four groups with the following incubation conditions: (a) 27 mM glucose, (b) 27 mM glucose and insulin, (c) 27 mM glucose and human recombinant (hr)C-peptide, and (d) 27 mM glucose, insulin, and hrC-peptide. After 24 hours, total RNA and protein were extracted from cells and subjected to reverse transcriptase-polymerase chain reaction and Western blot analysis, respectively. Intracellular Ca(2+) was examined under the four conditions, using the Fura 2 method. RESULTS: The least expression of endothelial NOS (eNOS) and inducible NOS (iNOS) in HCSMCs was observed in cells exposed to 27 mM glucose alone. Increased expression of eNOS and iNOS was found after treatment with insulin or hrC-peptide alone, and the maximal expression of eNOS and iNOS was detected in HCSMCs exposed to both insulin and hrC-peptide. Western blot analyses using eNOS and iNOS antibodies confirmed the RNA data. These effects are likely mediated by the insulin-induced and/or C-peptide-induced increase in intracellular Ca(2+). CONCLUSIONS: Our results demonstrated that C-peptide, in the presence of insulin, increases the expression of iNOS and eNOS in HCSMCs. These results suggest that C-peptide, especially in conjunction with insulin, may have beneficial effects on cavernosal smooth muscle relaxation.

Antibiotic soaked hydrophilic coated bioflex: a new strategy in the prevention of penile prosthesis infection.

OBJECTIVES: To find conditions that reduce the susceptibility of penile prostheses to infection, we studied the effect of coating the surface of polyurethane (Bioflex) with a hydrophilic material with and without antibiotics in decreasing bacterial colony counts both in vitro and in experiments in rats. MATERIALS AND METHODS: The in vitro experiment was performed using seven strips each of polyvinylpyrrolidone (PVP)-coated and uncoated polyurethane. These strips were dipped in saline for 5 minutes followed by incubation in a suspension of Staphylococcus epidermidis (SE) for a period of 10 minutes. Colony counts were determined after sonication of strips. For the in vitro experiments, 60 rats were used. Thirty animals each had uncoated or coated polyurethane implanted subcutaneously. In each group, strips were implanted after dipping them in either saline (N = 15) or an antibiotic solution (N = 15) consisting of 1 g/L vancomycin and 160 mg/L gentamicin. A bacterial suspension containing SE was then directly introduced into the subcutaneous pockets of all the animals prior to closure. After 7 days, strips were explanted along with 0.5 x 0.5 cm of surrounding tissue, and sonicated. Colony counts were performed on each sonicate. The data were analysed using Student's t-test. A P-value less than or equal to 0.05 was considered to be statistically significant. RESULTS: The in vitro study demonstrated a statistically significant (41%) reduction in the colony count of SE within the coated polyurethane strips compared to the uncoated Bioflex strips (150 +/- 44.7 CFU vs. 253 +/- 45.0 CFU, respectively, P-value < 0.05). Animal studies showed that bacterial CFU was highest in the uncoated Bioflex strip (29 +/- 24.5 CFU), followed by uncoated Bioflex with antibiotic treatment (24 +/- 28.1 CFU), coated Bioflex (17 +/- 25.2 CFU) and coated Bioflex with antibiotic treatment (13 +/- 16.1 CFU). Antibiotic treatment of coated Bioflex caused a significant reduction in the bacterial CFU compared to uncoated Bioflex (13 +/- 16.1 vs. 29 +/- 24.5 CFU, respectively, P = 0.04). This represents a 55% reduction in the bacterial count. While the reduction in the bacterial count in the coated Bioflex strip was not statistically different from that in the uncoated strip, a trend towards significance was noted with a 41% reduction (P > 0.05) in bacterial count in the coated Bioflex group compared to uncoated Bioflex. CONCLUSIONS: In conclusion, in vitro studies demonstrate a significant (41%) reduction in the colony count of SE in PVP-coated polyurethane compared to uncoated polyurethane. In vivo study in rats showed that antibiotic treatment of PVP-coated Bioflex resulted in a statistically significant reduction (55%) in colony count of SE compared to uncoated Bioflex.

Expression of cAMP-responsive element modulator (CREM) in rat testes following chronic cocaine administration.

OBJECTIVE: c-AMP-responsive element modulator (CREM), one of the nuclear factors involved in the regulation of gene expression by cAMP, has an important role in spermatogenesis. Our recent study has shown that chronic administration of cocaine to male rats results in disruption of spermatogenesis, including reduction of germ cells. As a further step toward understanding this process, we have studied the role of CREM in cocaine-induced testicular damage. MATERIALS AND METHODS: Sprague-Dawley rats were administered cocaine hydrochloride subcutaneously daily for 90 days. Control animals received equal volumes of normal saline daily for 90 days. Testes were removed after 15, 30, 90 days of cocaine administration. Total RNA was extracted from the testes and subjected to RT-PCR. Testicular tissue was also homogenized in a lysis buffer, and Western blotting was performed using anti-CREM antibody. RESULTS: RT-PCR analysis detected a single fragment of approximately 520 base pairs (bp) in control testes at all time points. The cocaine-treated testes showed reduced expression of CREM fragment. Western blot analysis using CREM antibodies confirmed the RNA data. There were reduced CREM proteins in the cocaine-treated testes compared with controls. CONCLUSIONS: The CREM gene is essential for spermatogenesis. Our results indicate that the reduction in testicular CREM expression may be one of the mechanisms responsible for disruption or impairment of spermatogenesis in the testes following chronic cocaine administration.

Role of mitochondrial cytochrome c in cocaine-induced apoptosis in rat testes.

OBJECTIVES: We have previously demonstrated that cocaine exposure leads to apoptosis in rat testes. To understand further the mechanism of cocaine-induced testicular damage, we studied the effect of cocaine on cytochrome c release from the mitochondria. We also determined the caspase 3, caspase 8, and caspase 9 activities in rat testes after chronic cocaine exposure. METHODS: Thirty-day-old male Sprague-Dawley rats received cocaine hydrochloride or equal volumes of normal saline subcutaneously daily for 90 days. The testes were removed at 15, 30, and 90 days of cocaine or saline administration. Mitochondria and cytosolic fractions from testes were isolated. Western blotting was performed in both fractions using anti-cytochrome c antibody. Caspase 3, caspase 8, and caspase 9 activities were determined by fluorometric assay. RESULTS: The expression of cytochrome c protein in the cytosolic fraction was increased on day 15 and persisted for up to 90 days after cocaine injection compared with controls. However, the expression of cytochrome c in testes was decreased in the mitochondria fraction on days 15, 30, and 90 after cocaine injections compared with the corresponding controls. The caspase activity study showed caspase 3 and caspase 9 activities increased in cocaine-treated testes at each point of the study compared with the corresponding controls. However, the caspase 8 activity in cocaine-treated testes did not change significantly at each point of the study compared with the corresponding controls. CONCLUSIONS: Our results suggest that the release of cytochrome c from mitochondria and its subsequent activation of caspase 9 and caspase 3 in testes play a key role in cocaine-induced germ cell apoptosis. Our findings also indicate that cocaine-induced testicular germ cell apoptosis in rats is at least initiated through a mitochondria-associated pathway.

Cigarette smoking induces apoptosis in rat testis.

In a previous studywe demonstrated the deleterious effect of cigarette smoke on spermatogenesis in the testis of peripubertal Sprague-Dawley rats. In this study we investigated the development of apoptosis as a possible contributing factor to the pathogenic mechanism underlying these effects. Peripubertal rats were exposed to cigarette smoke with the Walton Horizontal Smoking Machine. Similarly, age-matched control rats were exposed to room air with the smoking machine. Rats from both groups were sacrificed after 45 days of treatment and the testes were removed. Testes were stained utilizing the terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) staining technique. DNA fragmentation was further evaluated using gelectrophoresis. There was a significant increase in the incidence of apoptosis in the treated group compared to the control group as demonstrated by the larger amount of tubules containing > or = 3apoptotic bodies in the smoke-exposed group, that is, 36% versus 14% in the control group (p < 0.05). Agarose gel electrophoresis demonstrated the DNA ladder in the treated group but not in the control animals. In conclusion, chronic cigarette smoke induces apoptosis in the rat testis. Apoptosis may be one of the pathogenic mechanisms responsible for defective spermatogenesis in the rat following chronic cigarette smoking.