Dry eye is a common and frequently occurring ophthalmology disease with complex etiology and easy recurrence.Oral administration of traditional Chinese medicine has the characteristicsof high curative effect and littl...Dry eye is a common and frequently occurring ophthalmology disease with complex etiology and easy recurrence.Oral administration of traditional Chinese medicine has the characteristicsof high curative effect and little toxic and side effect in the treatment of dry eye.This paper collates the domestic reported clinical studies on the oral administration of traditional Chinese medicine in the treatment of dry eye,which are discussed from four aspects:special prescription for specific disease,addition and subtraction of main prescription,treatment based on syndrome differentiation and proprietary Chinese medicine.The curative effect and advantages of traditional Chinese medicine in the treatment of dry eye are demonstrated,providing a reference for the treatment of dry eye in the future.展开更多
Irritable bowel syndrome (IBS), a common disease of intestinal dysfunction, is also called emotional enteritis, mucous enteritis, irritable colon and so on1. It is often lingering with a long disease course and is eas...Irritable bowel syndrome (IBS), a common disease of intestinal dysfunction, is also called emotional enteritis, mucous enteritis, irritable colon and so on1. It is often lingering with a long disease course and is easy to recur. The author has in recent years treated 50 cases of the disease by oral administration of Chinese medicines and retention-enema, with satisfactory results reported as follows.展开更多
Hypertension has become a growing public health concern worldwide.In fact,hypertension is commonly associated with increased morbidity and mortality.Currently,oligonucleotide drugs have proven to be promising therapeu...Hypertension has become a growing public health concern worldwide.In fact,hypertension is commonly associated with increased morbidity and mortality.Currently,oligonucleotide drugs have proven to be promising therapeutic agents for various diseases.In the present study,we aimed to demonstrate that a herbal small RNA(s RNA),XKC-sRNA-h3(B55710460,F221.I000082.B11),exhibits potent antihypertensive effects by targeting angiotensin-converting enzyme(ACE)in mice.When compared with captopril,oral administration of the sphingosine(d18:1)-XKC-s RNA-h3 bencaosome more effectively prevented angiotensin II-induced hypertensive cardiac damage and alleviated kidney injury in mice.Such findings indicated that XKC-sRNA-h3 may be a novel orally available ACE inhibitor type oligonucleotide drug for hypertension.展开更多
Traditional Chinese medicine(TCM)believes that the main pathogenesis of ulcerative colitis is spleen deficiency;damp heat in the large intestine as the symptom,the treatment must be warming,clearing,eliminating,tonify...Traditional Chinese medicine(TCM)believes that the main pathogenesis of ulcerative colitis is spleen deficiency;damp heat in the large intestine as the symptom,the treatment must be warming,clearing,eliminating,tonifying,astringing concurrently.From the concept of combining holism and the local treatment in TCM,idea of combining internal and external treatment is adopted.That is,the external treatment follows the therapeutic principle of using herbs with a bitter and cold nature to eliminate stagnation,and the seven carbon decoction,which can clear heat and dampness,cool the blood,and stop dysentery,is used as a rectal drip to retain the enema.Internal treatment follows the therapeutic principle of warmly tonifying and cultivating vital qi,with oral Chinese herbal medicine named Maodie Tang to strengthen the spleen and tonify the kidney,clearing heat and inducing dampness.展开更多
Microglia,which are tissue-resident macrophages in the brain,play a central role in the brain innate immunity and contribute to the maintenance of brain homeostasis.Lipopolysaccharide is a component of the outer membr...Microglia,which are tissue-resident macrophages in the brain,play a central role in the brain innate immunity and contribute to the maintenance of brain homeostasis.Lipopolysaccharide is a component of the outer membrane of gram-negative bacteria,and activates immune cells including microglia via Toll-like receptor 4 signaling.Lipopolysaccharide is generally known as an endotoxin,as administration of highdose lipopolysaccharide induces potent systemic inflammation.Also,it has long been recognized that lipopolysaccharide exacerbates neuroinflammation.In contrast,our study revealed that oral administration of lipopolysaccharide ameliorates Alzheimer’s disease pathology and suggested that neuroprotective microglia are involved in this phenomenon.Additionally,other recent studies have accumulated evidence demonstrating that controlled immune training with low-dose lipopolysaccharide prevents neuronal damage by transforming the microglia into a neuroprotective phenotype.Therefore,lipopolysaccharide may not a mere inflammatory inducer,but an immunomodulator that can lead to neuroprotective effects in the brain.In this review,we summarized current studies regarding neuroprotective microglia transformed by immune training with lipopolysaccharide.We state that microglia transformed by lipopolysaccharide preconditioning cannot simply be characterized by their general suppression of proinflammatory mediators and general promotion of anti-inflammatory mediators,but instead must be described by their complex profile comprising various molecules related to inflammatory regulation,phagocytosis,neuroprotection,anti-apoptosis,and antioxidation.In addition,microglial transformation seems to depend on the dose of lipopolysaccharide used during immune training.Immune training of neuroprotective microglia using lowdose lipopolysaccharide,especially through oral lipopolysaccharide administration,may represent an innovative prevention or treatment for neurological diseases;however more vigorous studies are still required to properly modulate these treatments.展开更多
BACKGROUND Acute pancreatitis(AP)is a pancreatic inflammatory disorder that is commonly complicated by extrapancreatic organ dysfunction.Dachengqi decoction(DCQD)has a potential role in protecting the extrapancreatic ...BACKGROUND Acute pancreatitis(AP)is a pancreatic inflammatory disorder that is commonly complicated by extrapancreatic organ dysfunction.Dachengqi decoction(DCQD)has a potential role in protecting the extrapancreatic organs,but the optimal oral administration time remains unclear.AIM To screen the appropriate oral administration time of DCQD for the protection of extrapancreatic organs based on the pharmacokinetics and pharmacodynamics of AP rats.METHODS This study consisted of two parts.In the first part,24 rats were divided into a sham-operated group and three model groups.The four groups were intragastrically administered with DCQD(10 g/kg)at 4 h,4 h,12 h,and 24 h postoperatively,respectively.Tail vein blood was taken at nine time points after administration,and then the rats were euthanized and the extrapancreatic organ tissues were immediately collected.Finally,the concentrations of the major DCQD components in all samples were detected.In the second part,84 rats were divided into a sham-operated group,as well as 4 h,12 h,and 24 h treatment groups and corresponding control groups(4 h,12 h,and 24 h control groups).Rats in the treatment groups were intragastrically administered with DCQD(10 g/kg)at 4 h,12 h,and 24 h postoperatively,respectively,and rats in the control groups were administered with normal saline at the same time points.Then,six rats from each group were euthanized at 4 h and 24 h after administration.Serum amylase and inflammatory mediators,and pathological scores of extrapancreatic organ tissues were evaluated.RESULTS For part one,the pharmacokinetic parameters(C max,T max,T 1/2,and AUC 0→t)of the major DCQD components and the tissue distribution of most DCQD components were better when administering DCQD at the later(12 h and 24 h)time points.For part two,delayed administration of DCQD resulted in lower IL-6 and amylase levels and relatively higher IL-10 levels,and pathological injury of extrapancreatic organ tissues was slightly less at 4 h after administration,while the results were similar between the treatment and corresponding control groups at 24 h after administration.CONCLUSION Delayed administration of DCQD might reduce pancreatic exocrine secretions and ameliorate pathological injury in the extrapancreatic organs of AP rats,demonstrating that the late time is the optimal dosing time.展开更多
Background:To systematically evaluate the efficacy and safety of traditional Chinese medicine in the treatment of refractory gastroesophageal reflux.Methods:PubMed,The Cochrane Library,Embase,Web of Science,China Nati...Background:To systematically evaluate the efficacy and safety of traditional Chinese medicine in the treatment of refractory gastroesophageal reflux.Methods:PubMed,The Cochrane Library,Embase,Web of Science,China National Knowledge Infrastructure,Wanfang Database,China Science and Technology Journal Database and Chinese BioMedical Literature Database were searched for randomized controlled trials of traditional Chinese medicine in the treatment of refractory gastroesophageal reflux from database establishment time to December 2020.After two researchers independently screened the literature,extracted data and evaluated the bias risk included in the study,RevMan5.3 software was used for meta-analysis.Results:A total of 12 randomized controlled trials,were included,including 893 patients.The results of meta-analysis showed that the total effective rate of the treatment group(relative risk=1.28,95%confidence interval(CI)(1.19,1.38),P<0.00001),RGERDQ(refractory gastroesophageal reflux disease)score(mean difference(MD)=−3.35,95%CI(−4.13,−2.57),P<0.00001],acid reflux(acid in the stomach comes out of the mouth)[MD=−0.30,95%CI(−0.45,−0.15),P<0.00001],heartburn(the feeling that the heart is burned)(MD=−0.44,95%CI(−0.60,−0.29),P<0.00001,and retrosternal pain(MD=−0.27,95%CI(−0.44,−0.10),P<0.00001,belching(MD=−0.40,95%CI(−0.57,−0.24),P<0.00001],endoscopic mucosal score(MD=−0.62,95%CI(−0.78,−0.46),P<0.00001],the differences were statistically significant,and the effective rate of mucosal improvement under endoscopy was P=0.93>0.05,with no statistically significant difference.Conclusion:The current evidence shows that traditional Chinese medicine in the treatment of refractory gastroesophageal reflux disease is better than that of western medicine in the total effective rate,relieving acid reflux,heartburn,retrosternal pain and belching symptoms,but it is impossible to judge the improvement of mucosa under endoscope.Due to the limitations of the quality and quantity of included studies,more high-quality studies are needed to confirm the above conclusions.展开更多
Urea transporters(UT)play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics.Thus,UT inhibitors are promising for development as nove...Urea transporters(UT)play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics.Thus,UT inhibitors are promising for development as novel diuretics.In the present study,a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput screening.Optimization of the inhibitor led to the identifi-cation of a promising preclinical candidate,N-[4-(acetylamino)phenyl]-5-nitrofuran-2-carboxamide(1 H),with excellent in vitro UT inhibitory activity at the submicromolar level.The half maximal inhibitory concentrations of 1 H against UT-B in mouse,rat,and human erythrocyte were 1.60,0.64,and0.13 mmol/L,respectively.Further investigation suggested that 8 mmol/L 1 H more powerfully inhibited UT-A1 at a rate of 86.8%than UT-B at a rate of 73.9%in MDCK cell models.Most interestingly,we found for the first time that oral administration of 1 H at a dose of 100 mg/kg showed superior diuretic effect in vivo without causing electrolyte imbalance in rats.Additionally,1 H did not exhibit apparent toxicity in vivo and in vitro,and possessed favorable pharmacokinetic characteristics.1 H shows promise as a novel diuretic to treat hyponatremia accompanied with volume expansion and may cause few side effects.展开更多
Oral administration has been widely regarded as the most conve nient,quick and safe approach compared to other routes of drug delivery.However,oral absorption of drugs is often limited due to rigorous environments and...Oral administration has been widely regarded as the most conve nient,quick and safe approach compared to other routes of drug delivery.However,oral absorption of drugs is often limited due to rigorous environments and complex obstacles in gastrointestinal tract.Having received considerable attention,biomacromolecules have been applied for oral drug delivery to improve the bioavailability,which could be attributed to its stability and unique bioactivities,including intestinal adhesion,opening of epithelial tight junctions,inhibiting cell efflux and regulating relative protein expression.Specifically,enhancing intestinal permeability has been regarded as a promising strategy for improving bioavailability of oral drug delivery.In this review,a series of biomacromolecules and the related mechanisms of increasing intestinal permeability for enhanced oral bioavailability are comprehensively classified and elucidated.In addition,recent advances in biomacromolecules based oral delivery and related future directions are mentioned and predicted in this review article.展开更多
Hydrogel has been used for in suit gastric ulcer therapy by stopping bleeding,separating from ulcer from gastric fluids and providing extracellular matrix scaffold for tissue regeneration,however,this treatment guided...Hydrogel has been used for in suit gastric ulcer therapy by stopping bleeding,separating from ulcer from gastric fluids and providing extracellular matrix scaffold for tissue regeneration,however,this treatment guided with endoscopic catheter in most cases.Here,we developed an oral keratin hydrogel to accelerate the ulcer healing without endoscopic guidance,which can specially adhere to the ulcer because of the high-viscosity gel formation on the wound surface in vivo.Approximately 50%of the ulcer-adhesive keratin hydrogel can resident in ethanol-treated rat stomach within 12 h,while approximately 18%of them maintained in health rat stomach in the same amount of time.Furthermore,Keratin hydrogels accelerated the ethanol-induced gastric ulcer healing by stopping the bleeding,preventing the epithelium cells from gastric acid damage,suppressing inflammation and promoting re-epithelization.The oral administration of keratin hydrogel in gastric ulcer treatment can enhance the patient compliance and reduce the gastroscopy complications.Our research findings reveal a promising biomaterial-based approach for treating gastrointestinal ulcers.展开更多
Effects of antimicrobial peptides(AMP)added to diets on aquatic animal health and body function are influenced by multiple factors such as animal species,initial body weight,the dosage of AMP and feeding duration.Howe...Effects of antimicrobial peptides(AMP)added to diets on aquatic animal health and body function are influenced by multiple factors such as animal species,initial body weight,the dosage of AMP and feeding duration.However,there is limited knowledge on the relationship between these factors and the body function of aquatic animals.Here,we aimed to perform multiple meta-analyses to investigate the effects of dietary AMP on growth performance(feed conversion ratio[FCR],specific growth rate[SGR]),enzyme activity(superoxide dismutase activity[SOD],lysozyme activity[LSA]),disease resistance(cumulative survival rate[CSR],the expression of immune-related genes[GENE])and the abundance of gut microbiota(MICRO)from a pool of empirical studies.Additionally,the dose-effect model was applied to determine the optimal AMP dose,initial body weight and feeding duration to maximize body function.To conduct the meta-analyses,we included 34 publications that estimated 705 effect sizes across 21 fish,2 shrimp and 2 shellfish species.The results confirmed that the inclusion of AMP in the diet can significantly improve SGR,SOD,LSA,CSR and GENE and decrease FCR for aquatic animals.Interestingly,our findings implied a slight positive effect of AMP on MICRO albeit with a limited number of studies available on fish gut microbial communities.Although no significant linear or quadratic relationship was predicted by meta-regression,the dose-effect indicated that the optimal AMP doses for FCR,SGR,SOD and LSA were 707.5,750.0,1,050.0 and 937.5 mg/kg,respectively.Taken together,fish with an initial body weight of 30 g could be fed with a dose of 600 to 800 mg/kg for 2 mo when AMP-supplemented diets were applied in aquaculture,which can effectively improve body function and health while lowering aquafeed costs.In addition,more studies should address fish gut microbiota to delimitate the influence of dietary AMP on MICRO in the future.展开更多
Phenylketonuria(PKU),a disease resulting in the disability to degrade phenylalanine(Phe)is an inborn error with a 1 in 10,000 morbidity rate on average around the world which leads to neurotoxicity.As an potential alt...Phenylketonuria(PKU),a disease resulting in the disability to degrade phenylalanine(Phe)is an inborn error with a 1 in 10,000 morbidity rate on average around the world which leads to neurotoxicity.As an potential alternative to a protein-restricted diet,oral intake of engineered probiotics degrading Phe inside the body is a promising treatment,currently at clinical stage II(Isabella,et al.,2018).However,limited transmembrane transport of Phe is a bottleneck to further improvement of the probiotic’s activity.Here,we achieved simultaneous degradation of Phe both intracellularly and extracellularly by expressing genes encoding the Phe-metabolizing enzyme phenylalanine ammonia lyase(PAL)as an intracellularly free and a cell surface-immobilized enzyme in Escherichia coli Nissle 1917(EcN)which overcomes the transportation problem.The metabolic engineering strategy was also combined with strengthening of Phe transportation,transportation of PAL-catalyzed trans-cinnamic acid and fixation of released ammonia.Administration of our final synthetic strain TYS8500 with PAL both displayed on the cell surface and expressed inside the cell to the Pah^(F263S)PKU mouse model reduced blood Phe concentration by 44.4%compared to the control Ec N,independent of dietary protein intake.TYS8500 shows great potential in future applications for PKU therapy.展开更多
Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer,their inefficient therapeutic outcomes,serious adverse effects,and high cost of mass production remai...Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer,their inefficient therapeutic outcomes,serious adverse effects,and high cost of mass production remain crucial challenges.Herein,we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers(TFENs).These nanovehicles had desirable particle sizes(131 nm),exosome-like morphology,and negative zeta potentials.Furthermore,TFENs were found to contain large amounts of polyphenols,flavonoids,functional proteins,and lipids.Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species(ROS)amplification.The increased intracellular ROS amounts could not only trigger mitochondrial damage,but also arrest cell cycle,resulting in the in vitro anti-proliferation,anti-migration,and anti-invasion activities against breast cancer cells.Further mice investigations demonstrated that TFENs after intravenous(i.v.)injection or oral administration could accumulate in breast tumors and lung metastatic sites,inhibit the growth and metastasis of breast cancer,and modulate gut microbiota.This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v.and oral routes.展开更多
变应性鼻炎（AR）已成为了一个全球性的健康问题,发病率呈逐年增长趋势,其发病时可以影响患者的日常工作、生活及学习效率,WHO组织全球鼻科和变态反应科的学者编写了＂变应性鼻炎及其对哮喘的影响（Allergic rhinitis and its impact on...变应性鼻炎（AR）已成为了一个全球性的健康问题,发病率呈逐年增长趋势,其发病时可以影响患者的日常工作、生活及学习效率,WHO组织全球鼻科和变态反应科的学者编写了＂变应性鼻炎及其对哮喘的影响（Allergic rhinitis and its impact on asthma,ARIA）＂指南,展开更多
基金The study was supported by the Tianjin municipal health and Health Committee and Tianjin Administration of traditional Chinese Medicine(Scientific research project of integrated traditional Chinese and Western Medicine NO.2019027).
文摘Dry eye is a common and frequently occurring ophthalmology disease with complex etiology and easy recurrence.Oral administration of traditional Chinese medicine has the characteristicsof high curative effect and little toxic and side effect in the treatment of dry eye.This paper collates the domestic reported clinical studies on the oral administration of traditional Chinese medicine in the treatment of dry eye,which are discussed from four aspects:special prescription for specific disease,addition and subtraction of main prescription,treatment based on syndrome differentiation and proprietary Chinese medicine.The curative effect and advantages of traditional Chinese medicine in the treatment of dry eye are demonstrated,providing a reference for the treatment of dry eye in the future.
文摘Irritable bowel syndrome (IBS), a common disease of intestinal dysfunction, is also called emotional enteritis, mucous enteritis, irritable colon and so on1. It is often lingering with a long disease course and is easy to recur. The author has in recent years treated 50 cases of the disease by oral administration of Chinese medicines and retention-enema, with satisfactory results reported as follows.
基金the National Natural Science Foundation of China(81788101)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-022)+1 种基金the 111 Project(BP0820029)the CAMS Endowment Fund(2021-CAMSJZ001)。
文摘Hypertension has become a growing public health concern worldwide.In fact,hypertension is commonly associated with increased morbidity and mortality.Currently,oligonucleotide drugs have proven to be promising therapeutic agents for various diseases.In the present study,we aimed to demonstrate that a herbal small RNA(s RNA),XKC-sRNA-h3(B55710460,F221.I000082.B11),exhibits potent antihypertensive effects by targeting angiotensin-converting enzyme(ACE)in mice.When compared with captopril,oral administration of the sphingosine(d18:1)-XKC-s RNA-h3 bencaosome more effectively prevented angiotensin II-induced hypertensive cardiac damage and alleviated kidney injury in mice.Such findings indicated that XKC-sRNA-h3 may be a novel orally available ACE inhibitor type oligonucleotide drug for hypertension.
基金supported by the Clinical Effect Evaluation of Chinese Medicine on Moderately Active Ulcerative Colitis(2018YFC1705403).
文摘Traditional Chinese medicine(TCM)believes that the main pathogenesis of ulcerative colitis is spleen deficiency;damp heat in the large intestine as the symptom,the treatment must be warming,clearing,eliminating,tonifying,astringing concurrently.From the concept of combining holism and the local treatment in TCM,idea of combining internal and external treatment is adopted.That is,the external treatment follows the therapeutic principle of using herbs with a bitter and cold nature to eliminate stagnation,and the seven carbon decoction,which can clear heat and dampness,cool the blood,and stop dysentery,is used as a rectal drip to retain the enema.Internal treatment follows the therapeutic principle of warmly tonifying and cultivating vital qi,with oral Chinese herbal medicine named Maodie Tang to strengthen the spleen and tonify the kidney,clearing heat and inducing dampness.
基金This work was funded by Control of Innate Immunity Technology Research Association,a grant of Cross-ministerial Strategic Innovation Promotion Program,SIP-No.14533073(to GIS)from the Council for Science from Technology and Innovation(CSTI)in Cabinet Office of Japanese Government and the National Agriculture and Food Research Organization(NARO).
文摘Microglia,which are tissue-resident macrophages in the brain,play a central role in the brain innate immunity and contribute to the maintenance of brain homeostasis.Lipopolysaccharide is a component of the outer membrane of gram-negative bacteria,and activates immune cells including microglia via Toll-like receptor 4 signaling.Lipopolysaccharide is generally known as an endotoxin,as administration of highdose lipopolysaccharide induces potent systemic inflammation.Also,it has long been recognized that lipopolysaccharide exacerbates neuroinflammation.In contrast,our study revealed that oral administration of lipopolysaccharide ameliorates Alzheimer’s disease pathology and suggested that neuroprotective microglia are involved in this phenomenon.Additionally,other recent studies have accumulated evidence demonstrating that controlled immune training with low-dose lipopolysaccharide prevents neuronal damage by transforming the microglia into a neuroprotective phenotype.Therefore,lipopolysaccharide may not a mere inflammatory inducer,but an immunomodulator that can lead to neuroprotective effects in the brain.In this review,we summarized current studies regarding neuroprotective microglia transformed by immune training with lipopolysaccharide.We state that microglia transformed by lipopolysaccharide preconditioning cannot simply be characterized by their general suppression of proinflammatory mediators and general promotion of anti-inflammatory mediators,but instead must be described by their complex profile comprising various molecules related to inflammatory regulation,phagocytosis,neuroprotection,anti-apoptosis,and antioxidation.In addition,microglial transformation seems to depend on the dose of lipopolysaccharide used during immune training.Immune training of neuroprotective microglia using lowdose lipopolysaccharide,especially through oral lipopolysaccharide administration,may represent an innovative prevention or treatment for neurological diseases;however more vigorous studies are still required to properly modulate these treatments.
基金Supported by the National Natural Science Foundation of China,No.81603480 and No.81573857.
文摘BACKGROUND Acute pancreatitis(AP)is a pancreatic inflammatory disorder that is commonly complicated by extrapancreatic organ dysfunction.Dachengqi decoction(DCQD)has a potential role in protecting the extrapancreatic organs,but the optimal oral administration time remains unclear.AIM To screen the appropriate oral administration time of DCQD for the protection of extrapancreatic organs based on the pharmacokinetics and pharmacodynamics of AP rats.METHODS This study consisted of two parts.In the first part,24 rats were divided into a sham-operated group and three model groups.The four groups were intragastrically administered with DCQD(10 g/kg)at 4 h,4 h,12 h,and 24 h postoperatively,respectively.Tail vein blood was taken at nine time points after administration,and then the rats were euthanized and the extrapancreatic organ tissues were immediately collected.Finally,the concentrations of the major DCQD components in all samples were detected.In the second part,84 rats were divided into a sham-operated group,as well as 4 h,12 h,and 24 h treatment groups and corresponding control groups(4 h,12 h,and 24 h control groups).Rats in the treatment groups were intragastrically administered with DCQD(10 g/kg)at 4 h,12 h,and 24 h postoperatively,respectively,and rats in the control groups were administered with normal saline at the same time points.Then,six rats from each group were euthanized at 4 h and 24 h after administration.Serum amylase and inflammatory mediators,and pathological scores of extrapancreatic organ tissues were evaluated.RESULTS For part one,the pharmacokinetic parameters(C max,T max,T 1/2,and AUC 0→t)of the major DCQD components and the tissue distribution of most DCQD components were better when administering DCQD at the later(12 h and 24 h)time points.For part two,delayed administration of DCQD resulted in lower IL-6 and amylase levels and relatively higher IL-10 levels,and pathological injury of extrapancreatic organ tissues was slightly less at 4 h after administration,while the results were similar between the treatment and corresponding control groups at 24 h after administration.CONCLUSION Delayed administration of DCQD might reduce pancreatic exocrine secretions and ameliorate pathological injury in the extrapancreatic organs of AP rats,demonstrating that the late time is the optimal dosing time.
文摘Background:To systematically evaluate the efficacy and safety of traditional Chinese medicine in the treatment of refractory gastroesophageal reflux.Methods:PubMed,The Cochrane Library,Embase,Web of Science,China National Knowledge Infrastructure,Wanfang Database,China Science and Technology Journal Database and Chinese BioMedical Literature Database were searched for randomized controlled trials of traditional Chinese medicine in the treatment of refractory gastroesophageal reflux from database establishment time to December 2020.After two researchers independently screened the literature,extracted data and evaluated the bias risk included in the study,RevMan5.3 software was used for meta-analysis.Results:A total of 12 randomized controlled trials,were included,including 893 patients.The results of meta-analysis showed that the total effective rate of the treatment group(relative risk=1.28,95%confidence interval(CI)(1.19,1.38),P<0.00001),RGERDQ(refractory gastroesophageal reflux disease)score(mean difference(MD)=−3.35,95%CI(−4.13,−2.57),P<0.00001],acid reflux(acid in the stomach comes out of the mouth)[MD=−0.30,95%CI(−0.45,−0.15),P<0.00001],heartburn(the feeling that the heart is burned)(MD=−0.44,95%CI(−0.60,−0.29),P<0.00001,and retrosternal pain(MD=−0.27,95%CI(−0.44,−0.10),P<0.00001,belching(MD=−0.40,95%CI(−0.57,−0.24),P<0.00001],endoscopic mucosal score(MD=−0.62,95%CI(−0.78,−0.46),P<0.00001],the differences were statistically significant,and the effective rate of mucosal improvement under endoscopy was P=0.93>0.05,with no statistically significant difference.Conclusion:The current evidence shows that traditional Chinese medicine in the treatment of refractory gastroesophageal reflux disease is better than that of western medicine in the total effective rate,relieving acid reflux,heartburn,retrosternal pain and belching symptoms,but it is impossible to judge the improvement of mucosa under endoscope.Due to the limitations of the quality and quantity of included studies,more high-quality studies are needed to confirm the above conclusions.
基金supported by National Natural Science Foundation of China(Grant Nos.81620108029,81974083,and 81330074)Beijing Natural Science Foundation grant 7172113(China)
文摘Urea transporters(UT)play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics.Thus,UT inhibitors are promising for development as novel diuretics.In the present study,a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput screening.Optimization of the inhibitor led to the identifi-cation of a promising preclinical candidate,N-[4-(acetylamino)phenyl]-5-nitrofuran-2-carboxamide(1 H),with excellent in vitro UT inhibitory activity at the submicromolar level.The half maximal inhibitory concentrations of 1 H against UT-B in mouse,rat,and human erythrocyte were 1.60,0.64,and0.13 mmol/L,respectively.Further investigation suggested that 8 mmol/L 1 H more powerfully inhibited UT-A1 at a rate of 86.8%than UT-B at a rate of 73.9%in MDCK cell models.Most interestingly,we found for the first time that oral administration of 1 H at a dose of 100 mg/kg showed superior diuretic effect in vivo without causing electrolyte imbalance in rats.Additionally,1 H did not exhibit apparent toxicity in vivo and in vitro,and possessed favorable pharmacokinetic characteristics.1 H shows promise as a novel diuretic to treat hyponatremia accompanied with volume expansion and may cause few side effects.
基金the National Natural Science Foundation of China(No.51803152)Natural Science Foundation of Shanghai(No.19ZR1478800)。
文摘Oral administration has been widely regarded as the most conve nient,quick and safe approach compared to other routes of drug delivery.However,oral absorption of drugs is often limited due to rigorous environments and complex obstacles in gastrointestinal tract.Having received considerable attention,biomacromolecules have been applied for oral drug delivery to improve the bioavailability,which could be attributed to its stability and unique bioactivities,including intestinal adhesion,opening of epithelial tight junctions,inhibiting cell efflux and regulating relative protein expression.Specifically,enhancing intestinal permeability has been regarded as a promising strategy for improving bioavailability of oral drug delivery.In this review,a series of biomacromolecules and the related mechanisms of increasing intestinal permeability for enhanced oral bioavailability are comprehensively classified and elucidated.In addition,recent advances in biomacromolecules based oral delivery and related future directions are mentioned and predicted in this review article.
基金The authors acknowledge the financial assistance provided by the National Natural Science Foundation of China(11972099 and 31600770)the Venture&Innovation Support Program for Chongqing Overseas Returnees(cx2020079)+2 种基金the Visiting Scholar Foundation of Key Laboratory of Biorheological Science and Technology(Chongqing University),Ministry of Education(CQKLBST-2017-008)the research and development talent base subject of advantageous traditional Chinese medicine in Bijie City,Guizhou Province(RCJD2020-21)the projects in the National Science&Technology Pillar Program during the Twelfth Five-year Plan Period(2015BAI05B03).
文摘Hydrogel has been used for in suit gastric ulcer therapy by stopping bleeding,separating from ulcer from gastric fluids and providing extracellular matrix scaffold for tissue regeneration,however,this treatment guided with endoscopic catheter in most cases.Here,we developed an oral keratin hydrogel to accelerate the ulcer healing without endoscopic guidance,which can specially adhere to the ulcer because of the high-viscosity gel formation on the wound surface in vivo.Approximately 50%of the ulcer-adhesive keratin hydrogel can resident in ethanol-treated rat stomach within 12 h,while approximately 18%of them maintained in health rat stomach in the same amount of time.Furthermore,Keratin hydrogels accelerated the ethanol-induced gastric ulcer healing by stopping the bleeding,preventing the epithelium cells from gastric acid damage,suppressing inflammation and promoting re-epithelization.The oral administration of keratin hydrogel in gastric ulcer treatment can enhance the patient compliance and reduce the gastroscopy complications.Our research findings reveal a promising biomaterial-based approach for treating gastrointestinal ulcers.
文摘Effects of antimicrobial peptides(AMP)added to diets on aquatic animal health and body function are influenced by multiple factors such as animal species,initial body weight,the dosage of AMP and feeding duration.However,there is limited knowledge on the relationship between these factors and the body function of aquatic animals.Here,we aimed to perform multiple meta-analyses to investigate the effects of dietary AMP on growth performance(feed conversion ratio[FCR],specific growth rate[SGR]),enzyme activity(superoxide dismutase activity[SOD],lysozyme activity[LSA]),disease resistance(cumulative survival rate[CSR],the expression of immune-related genes[GENE])and the abundance of gut microbiota(MICRO)from a pool of empirical studies.Additionally,the dose-effect model was applied to determine the optimal AMP dose,initial body weight and feeding duration to maximize body function.To conduct the meta-analyses,we included 34 publications that estimated 705 effect sizes across 21 fish,2 shrimp and 2 shellfish species.The results confirmed that the inclusion of AMP in the diet can significantly improve SGR,SOD,LSA,CSR and GENE and decrease FCR for aquatic animals.Interestingly,our findings implied a slight positive effect of AMP on MICRO albeit with a limited number of studies available on fish gut microbial communities.Although no significant linear or quadratic relationship was predicted by meta-regression,the dose-effect indicated that the optimal AMP doses for FCR,SGR,SOD and LSA were 707.5,750.0,1,050.0 and 937.5 mg/kg,respectively.Taken together,fish with an initial body weight of 30 g could be fed with a dose of 600 to 800 mg/kg for 2 mo when AMP-supplemented diets were applied in aquaculture,which can effectively improve body function and health while lowering aquafeed costs.In addition,more studies should address fish gut microbiota to delimitate the influence of dietary AMP on MICRO in the future.
基金supported by the National Natural Science Foundation of China(21825804,31921006)the National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”,China(2018ZX09711002-019)the Shanghai Municipal Science and Technology Major Project and the National Key Research and Development Program of China(2018YFA0800603)。
文摘Phenylketonuria(PKU),a disease resulting in the disability to degrade phenylalanine(Phe)is an inborn error with a 1 in 10,000 morbidity rate on average around the world which leads to neurotoxicity.As an potential alternative to a protein-restricted diet,oral intake of engineered probiotics degrading Phe inside the body is a promising treatment,currently at clinical stage II(Isabella,et al.,2018).However,limited transmembrane transport of Phe is a bottleneck to further improvement of the probiotic’s activity.Here,we achieved simultaneous degradation of Phe both intracellularly and extracellularly by expressing genes encoding the Phe-metabolizing enzyme phenylalanine ammonia lyase(PAL)as an intracellularly free and a cell surface-immobilized enzyme in Escherichia coli Nissle 1917(EcN)which overcomes the transportation problem.The metabolic engineering strategy was also combined with strengthening of Phe transportation,transportation of PAL-catalyzed trans-cinnamic acid and fixation of released ammonia.Administration of our final synthetic strain TYS8500 with PAL both displayed on the cell surface and expressed inside the cell to the Pah^(F263S)PKU mouse model reduced blood Phe concentration by 44.4%compared to the control Ec N,independent of dietary protein intake.TYS8500 shows great potential in future applications for PKU therapy.
基金supported by the National Natural Science Foundation of China(82072060 and 81571807,China)the Fundamental Research Funds for the Central Universities(XDJK2019TY002 and 2020CDJQY-A041,China)+1 种基金the Natural Science Foundation Project of Chongqing(cstc2020jcyjmsxm X0292,China)the Venture&Innovation Support Program for Chongqing Overseas Returnees(cx2018029,China)。
文摘Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer,their inefficient therapeutic outcomes,serious adverse effects,and high cost of mass production remain crucial challenges.Herein,we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers(TFENs).These nanovehicles had desirable particle sizes(131 nm),exosome-like morphology,and negative zeta potentials.Furthermore,TFENs were found to contain large amounts of polyphenols,flavonoids,functional proteins,and lipids.Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species(ROS)amplification.The increased intracellular ROS amounts could not only trigger mitochondrial damage,but also arrest cell cycle,resulting in the in vitro anti-proliferation,anti-migration,and anti-invasion activities against breast cancer cells.Further mice investigations demonstrated that TFENs after intravenous(i.v.)injection or oral administration could accumulate in breast tumors and lung metastatic sites,inhibit the growth and metastasis of breast cancer,and modulate gut microbiota.This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v.and oral routes.
