Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse...Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.展开更多
AIM： To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. METHODS： The effect of SCFAs on cytokine rel...AIM： To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. METHODS： The effect of SCFAs on cytokine release from human neutrophils was studied with EHSA. SCFA- dependent modulation of NF-κB reporter activity was assessed in the human colon adenocarcinoma cell line, Colo320DM. Finally, the effect of SCFAs on gene expression and cytokine release, measured with RT-PCR and ELISA, respectively, was studied in mouse colon organ cultures established from colitic mice. RESULTS： Acetate, propionate and butyrate at 30 mmol/L decreased LPS-stimulated TNFα release from neutrophils, without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-κB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression, whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132, but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures. CONCLUSION： In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-κB reporter activity, immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate, in addition to butyrate, could be useful in the treatment of inflammatory disorders, including IBD.展开更多
Background:Interest in the use of natural feed additives as an alternative to antimicrobials in the poultry industry has increased in recent years because of the risk of bacterial resistance.One of the most studied gr...Background:Interest in the use of natural feed additives as an alternative to antimicrobials in the poultry industry has increased in recent years because of the risk of bacterial resistance.One of the most studied groups are polyphenolic compounds,given their advantages over other types of additives and their easy potentiation of effects when complexes are formed with metal ions.Therefore,the objective of the present study was to evaluate the impact of dietary supplementation of copper acetate(CA),curcumin(CR),and their combination(CA-CR)against Salmonella Typhimurium colonization,intestinal permeability,and cecal microbiota composition in broiler chickens through a laboratory Salmonella infection model.S.Typhimurium recovery was determined on day 10 post-challenge by isolating Salmonella in homogenates of the right cecal tonsil(12 chickens per group)on Xylose Lysine Tergitol-4(XLT-4)with novobiocin and nalidixic acid.Intestinal integrity was indirectly determined by the fluorometric measurement of fluorescein isothiocyanate dextran(FITC-d)in serum samples from blood obtained on d 10 post-S.Typhimurium challenge.Finally,microbiota analysis was performed using the content of the left caecal tonsil of 5 chickens per group by sequencing V4 region of 16S rRNA gene.Results:The results showed that in two independent studies,all experimental treatments were able to significantly reduce the S.Typhimurium colonization in cecal tonsils(CT,P<0.0001)compared to the positive control(PC)group.However,only CA-CR was the most effective treatment in reducing S.Typhimurium counts in both independent studies.Furthermore,the serum fluorescein isothiocyanate dextran(FITC-d)concentration in chickens treated with CR was significantly lower when compared to PC(P=0.0084),which is related to a decrease in intestinal permeability and therefore intestinal integrity.The effect of dietary treatments in reducing Salmonella was further supported by the analysis of 16S rRNA gene sequences using Linear discriminant analysis effect size(LEfSe)since Salmonella was significantly enriched in PC group(LDA score>2.0 and P<0.05)compared to other groups.In addition,Coprobacillus,Eubacterium,and Clostridium were significantly higher in the PC group compared to other treatment groups.On the contrary,Fecalibacterium and Enterococcus in CR,unknown genus of Erysipelotrichaceae at CA-CR,and unknown genus of Lachnospiraceae at CA were significantly more abundant respectively.Conclusions:CR treatment was the most effective treatment to reduce S.Typhimurium intestinal colonization and maintain better intestinal homeostasis which might be achieved through modulation of cecal microbiota.展开更多
The purpose of this study was to develop an extended-release(ER) matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combinati...The purpose of this study was to develop an extended-release(ER) matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combination of enteric polymer and hydrophilic polymer. Hypromellose acetate succinate(HPMCAS) and hydroxypropylcellulose(HPC) were selected as ER polymers for the ER matrix tablet(HPMCAS/HPC ER matrix tablet). Oxycodone hydrochloride was employed as a model drug. Dissolution properties of the HPMCAS/HPC ER matrix tablets were evaluated and were not affected by the pH of the test medium or paddle rotating speed.In a USP apparatus 3(bio-relevant dissolution method), dissolution profiles of the HPMCAS/HPC ER matrix tablets containing oxycodone hydrochloride were similar to that of the reference product(OxyC ontin). Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroP lus based on dissolution profiles from the USP apparatus 3. The plasma concentration-time profile simulated was similar to that of the reference product. These results suggest that the combination of HPMCAS and HPC shows a robust dissolution profile against pH and paddle rotating speed and indicates the appropriate extended-release profile in humans.展开更多
Objectives: The aim of this study was to verify mitigating effects of the antioxidants α tocopherol (Vitamin E) and ascorbic acid (Vitamin C) on lead induced renal toxicity in adult male Wistar rats. Methods: A total...Objectives: The aim of this study was to verify mitigating effects of the antioxidants α tocopherol (Vitamin E) and ascorbic acid (Vitamin C) on lead induced renal toxicity in adult male Wistar rats. Methods: A total of 36 mature male Wistar rats separated into 1 control group fed with rat feeds and water only and 3 study groups fed with 10 mg/ml of lead acetate, 10 mg/ml of lead acetate + 200 mg/2ml of vitamin C and 10 mg/ml of lead acetate + 100 mg/2ml of vitamin E respectively in addition to feds and water for 28 days were used. Blood samples were obtained for renal indices and the kidneys of all rats were harvested, weighed and prepared for histological examination. Result: The percentage weight gain was highest among control rats (20.70%), followed by lead + vitamin E group (18.42%), lead + vitamin C group (17.00%) and the least amongst the lead group (9.50%). The mean serum uric acid of 419.20 ± 35.80 μmol/L in the lead treatment group was significantly higher than 395.50 ± 15.35 μmol/L, 393.30 ± 14.16 μmol/L and 387.67 ± 14.56 μmol/L in the lead + vitamin C group, lead + vitamin E group and controls respectively. The extent and proportion of renal tissue damage was higher in the lead-treated group and the commonest renal abnormalities observed were tubular and interstitial damage seen in 90.00% of rats in the lead-treated group compared to 75.00% and 60.00% in the lead + vitamin C and the lead + vitamin E groups respectively while the control rats had a normal histological appearance. Conclusions: The sub-acute administration of lead acetate may have inhibitory effect on growth of animals, and adversely affect renal function and histology with uric acid as a more reliable marker of lead induced renal toxicity compared to urea and creatinine. The histologic parameters of tubulointerstitial abnormalities were also consistent with lead toxicity. Antioxidants were useful in reducing lead induced renal damage and growth inhibition with vitamin E producing a more potent effect compared to Vitamin C.展开更多
Lauramine is widely considered to be an asphaltene flocculant,but its effect on the modification of crude oil by PPDs has been little studied.In this paper,the effect of LA dosage on the rheology improvement of EVA PP...Lauramine is widely considered to be an asphaltene flocculant,but its effect on the modification of crude oil by PPDs has been little studied.In this paper,the effect of LA dosage on the rheology improvement of EVA PPDs(100 ppm)on Qinghai waxy crude oil was investigated through rheological measurement,wax precipitating analysis,granularity test and resins/asphaltenes FTIR analysis.Compared with pure EVA,the compounding of LA and EVA obviously enhances the agglomeration degree and reduces the number of fine wax crystals,thus further enhancing the rheology of the oil samples,and the best performance is at the LA dosage of 200 ppm.At relatively small LA dosages,the LA facilitates the adsorption of EVA molecules on the asphaltene surfaces,which favors the becoming of EVA/asphaltenes composite particles;but at relatively high LA dosages,the LA makes the asphaltenes more aggregated and disturbs the EVA adsorption on the asphaltenes,which is adverse for the formation of EVA/asphaltenes compound particles.The compound particles can serve as wax precipitating templates and significantly influence its morphology,thus further improving the crude oil rheology.In consequence,the rheology improvement of EVA PPDs on Qinghai waxy crude oil first increases and then decreases with increasing the LA dosage.展开更多
基金supported by the National Natural Science Foundation of China,Nos. 32260196 (to JY), 81860646 (to ZY) and 31860274 (to JY)a grant from Yunnan Department of Science and Technology,Nos. 202101AT070251 (to JY), 202201AS070084 (to ZY), 202301AY070001-239 (to JY), 202101AZ070001-012, and 2019FI016 (to ZY)。
文摘Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.
文摘AIM： To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. METHODS： The effect of SCFAs on cytokine release from human neutrophils was studied with EHSA. SCFA- dependent modulation of NF-κB reporter activity was assessed in the human colon adenocarcinoma cell line, Colo320DM. Finally, the effect of SCFAs on gene expression and cytokine release, measured with RT-PCR and ELISA, respectively, was studied in mouse colon organ cultures established from colitic mice. RESULTS： Acetate, propionate and butyrate at 30 mmol/L decreased LPS-stimulated TNFα release from neutrophils, without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-κB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression, whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132, but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures. CONCLUSION： In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-κB reporter activity, immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate, in addition to butyrate, could be useful in the treatment of inflammatory disorders, including IBD.
基金Research was supported in part by funds provided by USDA-NIFA Sustainable Agriculture Systems,Grant No.2019-69012-29905Title of Project:Empowering US Broiler Production for Transformation and Sustainability USDA-NIFA(Sustainable Agriculture Systems):No.2019-69012-29905.
文摘Background:Interest in the use of natural feed additives as an alternative to antimicrobials in the poultry industry has increased in recent years because of the risk of bacterial resistance.One of the most studied groups are polyphenolic compounds,given their advantages over other types of additives and their easy potentiation of effects when complexes are formed with metal ions.Therefore,the objective of the present study was to evaluate the impact of dietary supplementation of copper acetate(CA),curcumin(CR),and their combination(CA-CR)against Salmonella Typhimurium colonization,intestinal permeability,and cecal microbiota composition in broiler chickens through a laboratory Salmonella infection model.S.Typhimurium recovery was determined on day 10 post-challenge by isolating Salmonella in homogenates of the right cecal tonsil(12 chickens per group)on Xylose Lysine Tergitol-4(XLT-4)with novobiocin and nalidixic acid.Intestinal integrity was indirectly determined by the fluorometric measurement of fluorescein isothiocyanate dextran(FITC-d)in serum samples from blood obtained on d 10 post-S.Typhimurium challenge.Finally,microbiota analysis was performed using the content of the left caecal tonsil of 5 chickens per group by sequencing V4 region of 16S rRNA gene.Results:The results showed that in two independent studies,all experimental treatments were able to significantly reduce the S.Typhimurium colonization in cecal tonsils(CT,P<0.0001)compared to the positive control(PC)group.However,only CA-CR was the most effective treatment in reducing S.Typhimurium counts in both independent studies.Furthermore,the serum fluorescein isothiocyanate dextran(FITC-d)concentration in chickens treated with CR was significantly lower when compared to PC(P=0.0084),which is related to a decrease in intestinal permeability and therefore intestinal integrity.The effect of dietary treatments in reducing Salmonella was further supported by the analysis of 16S rRNA gene sequences using Linear discriminant analysis effect size(LEfSe)since Salmonella was significantly enriched in PC group(LDA score>2.0 and P<0.05)compared to other groups.In addition,Coprobacillus,Eubacterium,and Clostridium were significantly higher in the PC group compared to other treatment groups.On the contrary,Fecalibacterium and Enterococcus in CR,unknown genus of Erysipelotrichaceae at CA-CR,and unknown genus of Lachnospiraceae at CA were significantly more abundant respectively.Conclusions:CR treatment was the most effective treatment to reduce S.Typhimurium intestinal colonization and maintain better intestinal homeostasis which might be achieved through modulation of cecal microbiota.
文摘The purpose of this study was to develop an extended-release(ER) matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combination of enteric polymer and hydrophilic polymer. Hypromellose acetate succinate(HPMCAS) and hydroxypropylcellulose(HPC) were selected as ER polymers for the ER matrix tablet(HPMCAS/HPC ER matrix tablet). Oxycodone hydrochloride was employed as a model drug. Dissolution properties of the HPMCAS/HPC ER matrix tablets were evaluated and were not affected by the pH of the test medium or paddle rotating speed.In a USP apparatus 3(bio-relevant dissolution method), dissolution profiles of the HPMCAS/HPC ER matrix tablets containing oxycodone hydrochloride were similar to that of the reference product(OxyC ontin). Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroP lus based on dissolution profiles from the USP apparatus 3. The plasma concentration-time profile simulated was similar to that of the reference product. These results suggest that the combination of HPMCAS and HPC shows a robust dissolution profile against pH and paddle rotating speed and indicates the appropriate extended-release profile in humans.
文摘Objectives: The aim of this study was to verify mitigating effects of the antioxidants α tocopherol (Vitamin E) and ascorbic acid (Vitamin C) on lead induced renal toxicity in adult male Wistar rats. Methods: A total of 36 mature male Wistar rats separated into 1 control group fed with rat feeds and water only and 3 study groups fed with 10 mg/ml of lead acetate, 10 mg/ml of lead acetate + 200 mg/2ml of vitamin C and 10 mg/ml of lead acetate + 100 mg/2ml of vitamin E respectively in addition to feds and water for 28 days were used. Blood samples were obtained for renal indices and the kidneys of all rats were harvested, weighed and prepared for histological examination. Result: The percentage weight gain was highest among control rats (20.70%), followed by lead + vitamin E group (18.42%), lead + vitamin C group (17.00%) and the least amongst the lead group (9.50%). The mean serum uric acid of 419.20 ± 35.80 μmol/L in the lead treatment group was significantly higher than 395.50 ± 15.35 μmol/L, 393.30 ± 14.16 μmol/L and 387.67 ± 14.56 μmol/L in the lead + vitamin C group, lead + vitamin E group and controls respectively. The extent and proportion of renal tissue damage was higher in the lead-treated group and the commonest renal abnormalities observed were tubular and interstitial damage seen in 90.00% of rats in the lead-treated group compared to 75.00% and 60.00% in the lead + vitamin C and the lead + vitamin E groups respectively while the control rats had a normal histological appearance. Conclusions: The sub-acute administration of lead acetate may have inhibitory effect on growth of animals, and adversely affect renal function and histology with uric acid as a more reliable marker of lead induced renal toxicity compared to urea and creatinine. The histologic parameters of tubulointerstitial abnormalities were also consistent with lead toxicity. Antioxidants were useful in reducing lead induced renal damage and growth inhibition with vitamin E producing a more potent effect compared to Vitamin C.
基金financially supported by the National Natural Science Foundation of China(grant number 51774311,51904327)China Postdoctoral Science Foundation(grant number 2019TQ0354,2019M662468)。
文摘Lauramine is widely considered to be an asphaltene flocculant,but its effect on the modification of crude oil by PPDs has been little studied.In this paper,the effect of LA dosage on the rheology improvement of EVA PPDs(100 ppm)on Qinghai waxy crude oil was investigated through rheological measurement,wax precipitating analysis,granularity test and resins/asphaltenes FTIR analysis.Compared with pure EVA,the compounding of LA and EVA obviously enhances the agglomeration degree and reduces the number of fine wax crystals,thus further enhancing the rheology of the oil samples,and the best performance is at the LA dosage of 200 ppm.At relatively small LA dosages,the LA facilitates the adsorption of EVA molecules on the asphaltene surfaces,which favors the becoming of EVA/asphaltenes composite particles;but at relatively high LA dosages,the LA makes the asphaltenes more aggregated and disturbs the EVA adsorption on the asphaltenes,which is adverse for the formation of EVA/asphaltenes compound particles.The compound particles can serve as wax precipitating templates and significantly influence its morphology,thus further improving the crude oil rheology.In consequence,the rheology improvement of EVA PPDs on Qinghai waxy crude oil first increases and then decreases with increasing the LA dosage.
