Plant-Based Dietary Fibers and Polysaccharides as Modulators of Gut Microbiota in Intestinal and Lung Inflammation: Current State and Challenges.

Recent research has underscored the significant role of gut microbiota in managing various diseases, including intestinal and lung inflammation. It is now well established that diet plays a crucial role in shaping the composition of the microbiota, leading to changes in metabolite production. Consequently, dietary interventions have emerged as promising preventive and therapeutic approaches for managing these diseases. Plant-based dietary fibers, particularly polysaccharides and oligosaccharides, have attracted attention as potential therapeutic agents for modulating gut microbiota and alleviating intestinal and lung inflammation. This comprehensive review aims to provide an in-depth overview of the current state of research in this field, emphasizing the challenges and limitations associated with the use of plant-based dietary fibers and polysaccharides in managing intestinal and lung inflammation. By shedding light on existing issues and limitations, this review seeks to stimulate further research and development in this promising area of therapeutic intervention.

Effect of Wrist-Ankle Acupuncture on Postoperative Analgesia after Total Knee Arthroplasty.

OBJECTIVE: To evaluate the effect of wrist-ankle acupuncture (WAA) in pain and functional recovery after total knee arthroplasty (TKA). METHODS: From June to September 2020, 94 participants were included from the Second Hospital of Tangshan and randomly assigned to the WAA group (47 cases) and the sham WAA group (47 cases) by a random number table, receiving real or sham WAA treatment, respectively. The primary outcome measure involved the visual analogue scale (VAS) scores at rest and in motion. The secondary outcomes involved the range of motion (ROM) of the knee joints, straight-leg raising time, postoperative weight-bearing time, sufentanil consumption within 48 h of patient-controlled analgesia (PCA) pump, length of hospital stay, and postoperative complications. RESULTS: The VAS scores on the 3rd, 5th, and 7th postoperative days at rest and in motion was significantly lower in the WAA group than that of the sham WAA group (P<0.01). The ROM on the 1st, 2nd, and 3rd PODs was significantly higher in the WAA group than that of the sham WAA group (P<0.01). In comparison to the sham WAA group, the sufentanil consumption within 48 h of PCA pump was significantly less in the WAA group (156.3 ± 12.2 µg vs. 128.8 ± 9.8 µg, P<0.01). There was no significant difference in active straight-leg raising time, postoperative weight-bearing time, length of hospital stay, and postoperative complications between the two groups (P>0.05). CONCLUSIONS: WAA could alleviate post-TKA pain, improve knee joint function, and reduce the sufentanil consumption within 48 h of PCA pump. WAA is a safe and effective treatment in the perioperative analgesic management for TKA.

Comparative transcriptomics analysis reveals a calcineurin B-like gene to positively regulate constitutive and acclimated freezing tolerance in potato.

Freezing stress is a major limiting factor in crop production. To increase frost-hardiness of crops via breeding, deciphering the genes conferring freezing-tolerance is vital. Potato cultivars (Solanum tuberosum) are generally freezing-sensitive, but some potato wild species are freezing-tolerant, including Solanum commersonii, Solanum malmeanum and Solanum acaule. However, the underlying molecular mechanisms conferring the freezing-tolerance to the wild species remain to be deciphered. In this study, five representative genotypes of the above-mentioned species with distinct freezing-tolerance were investigated. Comparative transcriptomics analysis showed that SaCBL1-like (calcineurin B-like protein) was upregulated substantially in all of the freezing-tolerant genotypes. Transgenic overexpression and known-down lines of SaCBL1-like were examined. SaCBL1-like was shown to confer freezing-tolerance without significantly impacting main agricultural traits. A functional mechanism analysis showed that SaCBL1-like increases the expression of the C-repeat binding factor-regulon as well as causes a prolonged higher expression of CBF1 after exposure to cold conditions. Furthermore, SaCBL1-like was found to only interact with SaCIPK3-1 (CBL-interacting protein kinase) among all apparent cold-responsive SaCIPKs. Our study identifies SaCBL1-like to play a vital role in conferring freezing tolerance in potato, which may provide a basis for a targeted potato breeding for frost-hardiness.

Anatomic Risk Factors for Osteochondral Fracture of Acute First-Time Patellar Dislocation in Adolescents: A Retrospective Magnetic Resonance Imaging Study.

Objective: To analyze the risk factors for osteochondral fracture (OCF) of first-time acute patellar dislocation (APD) through measurements of patellofemoral anatomy in adolescents. Methods: In this prospective study, all patients were divided into two groups according to whether OCF was detected on magnetic resonance imaging (MRI): Group A (associated with OCF) and Group B (without OCF). Patellofemoral anatomy was evaluated with four aspects including trochlear/patellar dysplasia, patella location, patellofemoral matching, and morphologic classification. On MRI scans, trochlear facet asymmetry ratio (TFAR), lateral trochlear inclination (LTI), sulcus angle (SA), trochlear depth (TD), and patellar depth (PD) were measured to assess trochlear/patellar dysplasia. Insall-Salvati index (ISI), Caton-Deschamps index (CDI), Blackburne-Peel index (BPI), lateral patellofemoral angle (LPFA), patellar tilt angle (PTA), and lateral patellar displacement (LPD) were measured to show the location of patella. Patellofemoral matching was analyzed through the measurements of patellofemoral congruence angle (PFCA), patellofemoral index (PFI), and patellotrochlear index (PTI). Results: A total of ninety-four adolescents from 49 boys and 45 girls (mean age, 15 years; range, 10-18 years) with first-time APD were recruited and included in Group A (65) and Group B (29). The PFI (2.62 ± 0.51 vs. 2.10 ± 0.44) and PTI (0.28 ± 0.05 vs. 0.22 ± 0.07) were significantly higher in Group B than Group A (P < 0.05). There were no significant differences in other quantitative outcomes of the two groups (P > 0.05). The distribution of Dejour/Wiberg classification was statistically similar between the two groups (P > 0.05). Conclusions: Adolescent patients with first-time APD complicating OCF have closer morphologic features of patellofemoral dysplasia and patella location when compared to adolescents without OCF. Abnormal patellofemoral matching increases the risk of OCF after first-time APD in adolescents.

Moxibustion plus Acupuncture for the Treatment of Poststroke Shoulder Pain: A Randomized Controlled Pilot Study.

BACKGROUND: In China, 45% of stroke patients suffer from poststroke shoulder pain, which brings about many obstacles to further rehabilitation. To date, there have been a few studies evaluating the effects of acupuncture or massage in treating poststroke shoulder pain, and good effects have been shown. However, better clinical treatments are still needed. OBJECTIVE: To explore a more effective treatment for poststroke shoulder pain, the clinical effects of moxibustion plus acupuncture were assessed. METHODS: Sixty patients were randomly divided into the control and intervention groups. The control group received a standard stroke treatment protocol including acupuncture, and the intervention group was given moxibustion combined with acupuncture. The visual analogue scale (VAS), National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer motor assessment, Barthel Index, and 17-item Hamilton Rating Scale for Depression (HAMD-17) were applied, and differences were analyzed. RESULTS: After 4 weeks of treatment, compared with the control group, the intervention group demonstrated significant improvement in Fugl-Meyer motor assessment and HAMD-17 (both p < 0.01) as well as in the VAS, NIHSS, and Barthel Index (all p < 0.05). CONCLUSION: Moxibustion plus acupuncture treatment can alleviate poststroke shoulder pain, improve upper limb motor function and the ability to perform activities of daily living, and relieve patients' depression.

Salicylic Acid Improves the Constitutive Freezing Tolerance of Potato as Revealed by Transcriptomics and Metabolomics Analyses.

Freezing severely impacts potato production. Deciphering the pathways and metabolites that regulate the freezing tolerance of potato is useful in cultivation and breeding for hardiness. In the present study, Solanum acaule was identified to be more freezing tolerant than S. tuberosum. Furthermore, the two genotypes before/after exposure to 4 °C for 7 d with additional -1 °C for 12 h were analysed by RNA-seq and metabolomics, and the results were compared with the previous -1 °C for 12 h. The results showed that S. acaule activated numerous genes that differed from those of S. tuberosum. Among the genes, five pathways, such as the hormone signalling pathway, which includes salicylic acid, were enriched. Further metabolomics analysis showed that the content of salicylic acid was improved in S. acaule in response to -1 °C for 12 h. Moreover, exogenous application of 0.1 mM salicylic acid to potato was shown to improve constitutive freezing tolerance and increase the expression of HSFC1. Following transcriptome and metabolome analyses, it was documented that the content of SA that increased in freezing-tolerant S. acaule after exposure to cold condition, associated with the SA signalling pathway, enhanced potato freezing tolerance, probably through HSFC1.

Changes and Prognostic Value of lncRNA CASC9 in Patients with Advanced Colon Cancer after Chemotherapy.

OBJECTIVE: Colon cancer (CC) shows a gradual increasing incidence in recent years, and chemotherapy is a frequently adopted treatment for patients with middle or advanced colon cancer (ACC), but it lacks prognostic markers after CC. METHODS: The changes of lncRNA CASC9 in 58 patients with CC were determined using a real-time quantitative PCR (qRT-PCR) assay before and after chemotherapy, and the correlation of serum lncRNA CASC9 with efficacy of FOLFOX4 regimen (oxaliplatin + calcium folinate + fluorouracil) was analyzed. The patients were followed up to understand the association of lncRNA CASC9 with overall survival (OS) and progression-free survival (PFS). RESULTS: Patients with CC showed notably higher lncRNA CASC9 expression than controls, and lncRNA CASC9 presented an association with the clinical stage of the patients. In addition, lncRNA CASC9 demonstrated a clinical value in predicting efficacy on patients and acted as one independent prognostic factor for PFS in patients with ACC. CONCLUSIONS: With increased expression of serum lncRNA CASC9, patients with ACC suffered an unfavorable chemotherapy effect. In addition, serum lncRNA CASC9 is a promising sensitive indicator for prediction of ACC and is related to the clinical efficacy and prognosis of patients.

A γ-glutamylcysteine ligase AcGCL alleviates cadmium-inhibited fructooligosaccharides metabolism by modulating glutathione level in Allium cepa L.

Fructooligosaccharides (FOS) are important carbohydrates in plants. Cadmium (Cd) toxicity limits growth and development in several plant species. Whether FOS metabolism is affected by Cd and the molecular mechanisms of tolerance of the effects of Cd toxicity in plants remain enigmatic. In the present study, FOS metabolism was analyzed under Cd stress in onion (Allium cepa L.). Results showed that Cd stress can inhibit FOS accumulation in onion, followed by the upregulation of a putative onion γ-glutamylcysteine ligase gene AcGCL. Heterologous expression of the AcGCL protein in Escherichia coli revealed that this recombinant enzyme has GCL activity. Furthermore, overexpressing AcGCL significantly increased glutathione (GSH) accumulation in young onion roots under Cd treatment, accompanied by increased phytochelatin (PC) amount, and increased transcript expression of GSH synthetase (GS), and phytochelatin synthase (PCS) genes. Notably, compared with control, overexpressing AcGCL ameliorated Cd phytotoxicity on onion FOS metabolism, which correlated with increased FOS synthesis. Taken together, these results suggest that the function of AcGCL as a γ-glutamylcysteine ligase can alleviate Cd inhibited FOS metabolism by modulating GSH levels in onion.

A randomized double-blind placebo-controlled multicenter trial of Bushen Yisui and Ziyin Jiangzhuo formula for constipation in Parkinson disease.

INTRODUCTION: Constipation is a common nonmotor symptom of Parkinson disease (PD). Constipation can also impact patient's quality of life. Chinese herbal medicines have been used for the treatment of constipation in PD. This trial will evaluate the efficacy and safety of a Chinese herbal formula Bushen Yisui and Ziyin Jiangzhuo (BYZJ) for the treatment of constipation in PD. METHODS AND ANALYSIS: This randomized, double-blind, placebo-controlled, multicenter clinical trial will involve 4 hospitals in Beijing, China. The study will aim to recruit 90 PD patients with constipation between 30 and 80 years-of age with a score of 1 - 4 on the Hoehn and Yahr scale. Once recruited, Patients will be randomized into a BYZJ group or a placebo group in a 2:1 ratio. The trial will include a 1-week run-in period, a 4-week double-blind treatment period, a 4-week and a 12-week follow-up period. All patients will be educated about PD-related constipation during the run-in period. BYZJ granules and simulated granules will be administered twice daily for 4 weeks to the BYZJ group and the placebo group respectively. Assessments will be performed during run-in period, before the start of treatment (baseline, week 0), and at 4, 8, and 16 weeks. The primary outcome will be measured with the Constipation Severity Instrument, and secondary outcomes will be evaluated with the Patient Assessment of Constipation Quality of Life questionnaire, Bristol Stool Form Scale, Movement Disorders-Unified Parkinson Disease Rating Scale, Nonmotor Symptoms Scale, PD Sleep Scale, Parkinson Fatigue Scale-16. Laxative use (dose and frequency) will also be recorded. Intention-to-treat and per-protocol set analyses will be used to compare symptom improvement between the 2 groups. Any adverse events will be recorded. DISCUSSION: If found effective and safe, BYZJ formula will be one of Chinese herb to treat constipation and even other nonmotor or motor symptoms in PD patients. The results will sustain the broader use of BYZJ formula in PD.

Xiaoyaosan Produces Antidepressant Effects in Rats via the JNK Signaling Pathway.

BACKGROUND: Xiaoyaosan (XYS) has achieved definite curative effects in clinic. However, the mechanism is not clear. Previous studies of our team indicated XYS improved anxiety-like behaviors through inhibiting c-Jun N-terminal kinase (JNK) signaling pathway of hippocampus. OBJECTIVES: In the study, we explored whether the JNK signaling pathway is involved in the mechanism of XYS treating depression. METHOD: Forty-eight rats were divided randomly into 4 groups (n = 12): the control group (deionized water, p.o.), the model group (deionized water, p.o.), the fluoxetine group (2.08 mg/kg/day, p.o.), and the XYS group (3.9 g/kg/day, p.o.). All rats except for the control group were given continuous 21 days of chronic immobilization stress (CIS; 3 h/day). On day 29, the body weights and the behavioral tests, including the novelty suppressed feeding test, the open field test, and the elevated plus maze test, were measured. On day 30, all the rats were sacrificed, and three indices of the JNK signaling pathway were tested by Western blot. RESULTS: The body weight and behavioral tests of all groups indicated that 21 days of CIS induced depression-like behaviors. After 21 days of treatment with fluoxetine and XYS, changes were seen in body weight, behaviors, and JNK, phosphorylated JNK (P-JNK), and phosphorylated c-Jun (P-c-Jun) levels in the hippocampus. CONCLUSIONS: XYS ameliorated the depression-like behaviors, potentially through affecting the JNK signaling pathway in the hippocampus.

The Chrysanthemum nankingense Genome Provides Insights into the Evolution and Diversification of Chrysanthemum Flowers and Medicinal Traits.

The Asteraceae (Compositae), a large plant family of approximately 24 000-35 000 species, accounts for ∼10% of all angiosperm species and contributes a lot to plant diversity. The most representative members of the Asteraceae are the economically important chrysanthemums (Chrysanthemum L.) that diversified through reticulate evolution. Biodiversity is typically created by multiple evolutionary mechanisms such as whole-genome duplication (WGD) or polyploidization and locally repetitive genome expansion. However, the lack of genomic data from chrysanthemum species has prevented an in-depth analysis of the evolutionary mechanisms involved in their diversification. Here, we used Oxford Nanopore long-read technology to sequence the diploid Chrysanthemum nankingense genome, which represents one of the progenitor genomes of domesticated chrysanthemums. Our analysis revealed that the evolution of the C. nankingense genome was driven by bursts of repetitive element expansion and WGD events including a recent WGD that distinguishes chrysanthemum from sunflower, which diverged from chrysanthemum approximately 38.8 million years ago. Variations of ornamental and medicinal traits in chrysanthemums are linked to the expansion of candidate gene families by duplication events including paralogous gene duplication. Collectively, our study of the assembled reference genome offers new knowledge and resources to dissect the history and pattern of evolution and diversification of chrysanthemum plants, and also to accelerate their breeding and improvement.

Corilagin sensitizes epithelial ovarian cancer to chemotherapy by inhibiting Snail­glycolysis pathways.

We identified that corilagin is a major component extracted from a well-known hepatoprotective and antiviral medicinal herb, Phyllanthus niruri L with antitumor activity. Our previous study found that corilagin inhibited the growth of ovarian cancer cells via the TGF-ß/AKT/ERK signaling pathways. Recently, we demonstrated that corilagin enhanced the sensitivity of ovarian cancer cells to chemotherapy. Ovarian cancer cell lines, SKOv3ip, Hey and HO-8910PM-Snail, were treated with different concentrations of corilagin in combination with paclitaxel and carboplatin. Corilagin distinctly enhanced the inhibitory effects of paclitaxel and carboplatin. To understand the mechanisms involved in the chemo-sensitization by corilagin, we performed reverse phase protein array analysis to determine the signaling networks induced by corilagin. We observed that both paclitaxel and carboplatin upregulated the expression levels of several apoptotic and death-related proteins, such as caspase 3, caspase 7 and PDCD4, which were further enhanced when combined with corilagin. Meanwhile, corilagin induced distinct pathways to paclitaxel and carboplatin treatment. We also performed isobaric tags for relative and absolute quantitation proteomics analysis in corilagen-treated ovarian cancer cells. This analysis indicated that corilagin is mainly involved in the glycolysis pathway. Seahorse XF96 extracellular acidification rate analysis confirmed that corilagin inhibited glycolysis by downregulation of CD44 and STAT3. In summary, our observations indicate that corilagin sensitized epithelial ovarian cancer cells to paclitaxel and carboplatin treatment by primarily inhibiting Snail-glycolysis pathways. Corilagin is a herbal medicine with low toxic effects to normal cells, particularly hepatoprotective, and may be an ideal complimentary medicine when combined with highly toxic chemotherapeutic agents.

Effects of Refined Xiaoyaosan on Depressive-Like Behaviors in Rats with Chronic Unpredictable Mild Stress through Neurosteroids, Their Synthesis and Metabolic Enzymes.

Abstract: To observe the effects of refined Xiaoyaosan (XYS) on the depressive-like behaviors in rats with chronic unpredictable mild stress (CUMS), and to explore the relationship between the changes of neurosteroids and mRNA expressions of their synthesis and metabolic enzymes, and the mechanism of XYS in the treatment of depression. Methods: Eighty-four healthy male Sprague-Dawley rats were randomly divided into normal group, model group, XYS group and fluoxetine group. The latter three groups were subjected to 21 days of CUMS to prepare the stress depression model. Rats in the XYS group, and fluoxetine group were given intragastric administration with refined XYS and fluoxetine, respectively. The behavioral changes of the rats were observed after 21 days. The contents of pregnenolone (PREG), progesterone (PROG) and alloprognanolone (ALLO) in the plasma of rats were measured by ELISA. The levels of PREG, PROG and ALLO in the hippocampus and amygdala tissues were measured by LC-MS/MS. The mRNA expressions of 3α-hydroxysteroid dehydrogenase (3α-HSD), 3ß-hydroxysteroid dehydrogenase (3ß-HSD), cholesterol side-chain cleavage enzyme (P450scc) and 5α-reductase (5a-R) in the hippocampus and amygdala were detected by RT-qPCR methods. Results: There were changes in the model rats. The contents of PREG, PROG and ALLO changed similarly, which reflected in the decrease of PROG and ALLO, and the increase of PREG. The mRNA expression of P450scc was increased, and the mRNA expressions of 3α-HSD, 3ß-HSD and 5a-R were decreased. Refined XYS could improve the behaviors of rats and the biological indicators. Conclusions: There is a neurosteroid dysfunction in the brain region of depression rat model animals, and the mechanism of refined XYS depression treatment may be related to the regulation of the control of mRNA expression of related synthesis and metabolic enzymes in the hippocampus and amygdala, further affecting the contents of neurosteroids.

Xiao Yao San Improves the Anxiety-Like Behaviors of Rats Induced by Chronic Immobilization Stress: The Involvement of the JNK Signaling Pathway in the Hippocampus.

The current study evaluated the effects of Xiao Yao San (XYS) on anxiety-like behaviors and sought to determine whether the c-Jun N-terminal kinase (JNK) signaling pathway is involved. A total of 40 rats were divided into 5 groups (n=8): the control group (deionized water, per os (p.o.)), the model group (deionized water, p.o.), the SP600125 group (surgery), the per se group (surgery), and the XYS group (3.9 g/kg/d, p.o.). A 1% dimethyl sulfoxide (DMSO) citrate buffer solution (2 µL/ventricle/d) and SP600125 (10 µg/ventricle, 2 µL/ventricle/d) were separately and bilaterally injected into the rats of the two surgery groups via the ventricular system of the brain. All but the control group underwent 14 d of chronic immobilization stress (CIS; 3 h/d). On day 15, the body weights of all of the rats were measured; additionally, the rats were subjected to the elevated plus maze (EPM) and novelty suppressed feeding (NSF) tests. Finally, JNK signaling pathway indices, including phosphorylated JNK (P-JNK), JNK, phosphorylated c-Jun (P-c-Jun) and cytochrome C (Cyt-C), were examined. After modeling, the body weight and behavioral analyses of the model rats indicated that this modeling method induced anxiety-like behaviors. P-JNK, JNK, and P-c-Jun were altered in the hippocampus of the model rats. After 14 d of treatment with XYS and SP600125, rat body weight and behaviors as well as P-JNK, JNK, and P-c-Jun had changed. However, no significant difference in Cyt-C was found. XYS improves the anxiety-like behaviors induced by CIS, which might be related to the JNK signaling pathway in the hippocampus.

Effects of Xiaoyaosan on Stress-Induced Anxiety-Like Behavior in Rats: Involvement of CRF1 Receptor.

Background. Compared with antidepressant activity of Xiaoyaosan, the role of Xiaoyaosan in anxiety has been poorly studied. Objective. To observe the effects of Xiaoyaosan on anxiety-like behavior induced by chronic immobilization stress (CIS) and further explore whether these effects were related to CRF1R signaling. Methods. Adult male SD rats were randomly assigned to five groups (n = 12): the nonstressed control group, vehicle-treated (saline, p.o.) group, Xiaoyaosan-treated (3.854 g/kg, p.o.) group, vehicle-treated (surgery) group, and antalarmin-treated (surgery) group. Artificial cerebrospinal fluid (0.5 µL/side) or CRF1R antagonist antalarmin (125 ng/0.5 µL, 0.5 µL/side) was bilaterally administered into the basolateral amygdala in the surgery groups. Except for the nonstressed control group, the other four groups were exposed to CIS (14 days, 3 h/day) 30 minutes after treatment. On days 15 and 16, all animals were subjected to the elevated plus-maze (EPM) and novelty suppressed feeding (NSF) test. We then examined the expression of CRF1R, pCREB, and BDNF in the amygdala. Results. Chronic pretreatment with Xiaoyaosan or antalarmin significantly reversed elevated anxiety-like behavior and the upregulated level of CRF1R and BDNF in the amygdala of stressed rats. pCREB did not differ significantly among the groups. Conclusions. These results suggest that Xiaoyaosan exerts anxiolytic-like effects in behavioral tests and the effects may be related to CRF1R signaling in the amygdala.

TCM Formula Xiaoyaosan Decoction Improves Depressive-Like Behaviors in Rats with Type 2 Diabetes.

The mechanism of depression with type 2 diabetes remains elusive, requiring further study. Objective. To evaluate the effect of TCM formula Xiaoyaosan on depressive-like behaviors in rats with type 2 diabetes. Methods. Rats were divided into 5 groups and drugs were administered during the model period of 21 days. The model of depressive-like behaviors in rats with type 2 diabetes was induced by a high fat diet, low doses of STZ injection, and chronic restraint stress for 21 days. The body weight, fasting blood glucose, ITT, OGTT, 5-HT, DA, depression behaviors, and morphological changes of formation were measured and observed. Results. After modeling, marked changes were found in model rats; behavioral analyses of rats indicated that this modeling method negatively impacts locomotor function. In the H&E staining, changes were found predominately in the CA1 and DG subregions of the hippocampus. After 21 days of treatment by fluoxetine and Xiaoyaosan, rats' body weights, behaviors and fasting blood glucose, and hippocampal formation were modified. Conclusions. A new model of depressive-like behaviors in rats with type 2 diabetes was successfully created. Xiaoyaosan and fluoxetine in this study independently contribute to exacerbate the disease progression.

Effects of feeding ß-carotene on levels of ß-carotene and vitamin A in blood and tissues of beef cattle and the effects on beef quality.

The effects of feeding ß-carotene (ßC) on levels of ßC and vitamin A (retinol) in blood and tissues, and on beef quality, were evaluated in 120 steers. Each steer received supplementary ßC (at concentrations of 0, 600, 1200, or 1800 mg/day) for 90 days and then received no supplementary ßC for 60 days. ßC significantly increased in blood serum, liver, and subcutaneous and omental fat; linearly increased in the intestine and muscle; and remained unchanged in perirenal fat during supplementation. Differences between treatment groups were eliminated in subcutaneous and omental fat and in the liver by days 120 and 150, respectively, but remained significant at day 150 in blood. Retinol increased significantly in the liver and intestine during supplementation. Intramuscular fat content, meat color, and retinol in blood, muscle, or adipose tissues were not affected. Backfat thickness decreased slightly with increasing ßC supplementation and significantly differed between groups during depletion.

ATP-mediated potassium recycling in the cochlear supporting cells.

UNLABELLED: Gap junction-mediated K(+) recycling in the cochlear supporting cell has been proposed to play a critical role in hearing. However, how potassium ions enter into the supporting cells to recycle K(+) remains undetermined. In this paper, we report that ATP can mediate K(+) sinking to recycle K(+) in the cochlear supporting cells. We found that micromolar or submicromolar levels of ATP could evoke a K(+)-dependent inward current in the cochlear supporting cells. At negative membrane potentials and the resting membrane potential of -80 mV, the amplitude of the ATP-evoked inward current demonstrated a linear relationship to the extracellular concentration of K(+), increasing as the extracellular concentration of K(+) increased. The inward current also increased as the concentration of ATP was increased. In the absence of ATP, there was no evoked inward current for extracellular K(+) challenge in the cochlear supporting cells. The ATP-evoked inward current could be inhibited by ionotropic purinergic (P2X) receptor antagonists. Application of pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, 50 microM) or pre-incubation with an irreversible P2X7 antagonist oxidized ATP (oATP, 0.1 mM) completely abolished the ATP-evoked inward current at the negative membrane potential. ATP also evoked an inward current at cell depolarization, which could be inhibited by intracellular Cs(+) and eliminated by positive holding potentials. Our data indicate that ATP can activate P2X receptors to recycle K(+) in the cochlear supporting cells at the resting membrane potential under normal physiological and pathological conditions. This ATP-mediated K(+) recycling may play an important role in the maintenance of cochlear ionic homeostasis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11302-010-9184-9) contains supplementary material, which is available to authorized users.