D-galactose has been widely used in aging research because of its efficacy in inducing senescence and accelerating aging in animal models. The present study investigated the benefits of exercise for preventing neurode...D-galactose has been widely used in aging research because of its efficacy in inducing senescence and accelerating aging in animal models. The present study investigated the benefits of exercise for preventing neurodegeneration, such as synaptic plasticity, spatial learning and memory abilities, in mouse models of aging. D-galactose-induced aging mice were administered daily subcutaneous injections of D-galactose at the base of the neck for 10 consecutive weeks. Then, the mice were subjected to exercise training by running on a treadmill for 6 days a week. Shortened escape latency in a Morris water maze test indicated that exercise improved learning and memory in aging mice. The ameliorative changes were likely induced by an upregulation of Bcl-2 and brain-derived neurotrophic factor, the repression of apoptosis factors such as Fas and Bax, and an increase in the activity of glucose transporters-1 and 4. The data suggest moderate exercise may retard or inhibit neurodegeneration in D-galactose-induced aging mice.展开更多
Why neurogenesis is attenuated in elderly individuals is an intriguing question that has raised renewed interest.Mechanisms associated with declined neurogenesis in the aged brain have been attributed to inflammatory ...Why neurogenesis is attenuated in elderly individuals is an intriguing question that has raised renewed interest.Mechanisms associated with declined neurogenesis in the aged brain have been attributed to inflammatory cytokines[1].More recently,a specific role for interferon-y(IFN-y)produced by CD8-expressing cytotoxic T cells has been implicated[2].These observations suggest a scenario in which neurogenesis,at least in part,is regulated by immune cells within the aging brain.This raises several interesting questions with regards to the characteristics of specific immune cells within the brain,the signals for their expansion and maintenance,and their role in affecting neurogenesis and cognition during normal brain aging.展开更多
Until recently, little was known about the fungi found in shark gills and their biomedicinal potential. In this article, we described the isolation, bioactivity, diversity, and secondary metabolites of bioactive fungi...Until recently, little was known about the fungi found in shark gills and their biomedicinal potential. In this article, we described the isolation, bioactivity, diversity, and secondary metabolites of bioactive fungi from the gill of a shark （Carcharodon carcharias）. A total of 115 isolates were obtained and grown in 12 culture media. Fifty-eight of these isolates demonstrated significant activity in four antimicrobial, pesticidal, and cytotoxic bioassay models. Four randomly selected bioactive isolates inhibited human cancer cell proliferation during re-screening. These active isolates were segregated into 6 genera using the internal transcribed spacer-large subunit （ITS-LSU） rDNA-sequence BLAST comparison. Four genera, Penicillium, Aspergillus, Mucor, and Chaetomium were the dominant taxa. A phylogenic tree illustrated their intergenera and intragenera genetic diversity. HPLC-DAD-HRMS analysis and subsequent database searching revealed that nine representative strains produced diverse bioactive compound profiles. These results detail the broad range of bioactive fimgi found in a shark＇s gills, revealing their biopharmaceutical potential. To the best of our knowledge, this is the first study characterizing shark gill fungi and their bioactivity.展开更多
BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy optio...BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy options are still lacking.Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1(NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis,but its role in diseases including hepatic fibrosis remains undefined.Therefore,additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment.AIM To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1.METHODS Twenty-four male C57BL/6 mice were randomized and separated into three groups,comprising the normal,fibrosis,and calcitriol treatment groups,and liver fibrosis was modeled by carbon tetrachloride(CCl4).To evaluate the level of hepatic fibrosis in every group,serological and pathological examinations of the liver were conducted.TGF-β1 was administered to boost the in vitro cultivation of LX-2 cells.NS3TP1,α-smooth muscle actin(α-SMA),collagen I,and collagen Ⅲ in every group were examined using a Western blot and real-time quantitative polymerase chain reaction.The activity of the transforming growth factor beta 1(TGFβ1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected.The statistical analysis of the data was performed using the Student’s t test.RESULTS NS3TP1 promoted the activation,proliferation,and differentiation of hepatic stellate cells(HSCs)and enhanced hepatic fibrosis via the TGFβ1/Smad3 and NF-κB signaling pathways,as evidenced by the presence of α-SMA,collagen I,collagen Ⅲ,p-smad3,and p-p65 in LX-2 cells,which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference.The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression,as shown by the luciferase assay.NS3TP1 inhibited the apoptosis of HSCs.Moreover,both Smad3 and p65 could bind to NS3TP1,and p65 increased the promoter activity of NS3TP1,while NS3TP1 increased the promoter activity of TGFβ1 receptor I,as indicated by coimmunoprecipitation and luciferase assay results.Both in vivo and in vitro,treatment with calcitriol dramatically reduced the expression of NS3TP1.Calcitriol therapy-controlled HSCs activation,proliferation,and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice.Furthermore,calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1.CONCLUSION Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique,prospective therapeutic target in hepatic fibrosis.展开更多
In Scandinavia, tick-borne infections affecting humans include Lyme borreliosis (LB), tick-borne encephalitis (TBE) and human granulocytic anaplasmosis (HGA). Each of these infections can present with unspecific sympt...In Scandinavia, tick-borne infections affecting humans include Lyme borreliosis (LB), tick-borne encephalitis (TBE) and human granulocytic anaplasmosis (HGA). Each of these infections can present with unspecific symptoms. In this prospective clinical study, we recruited patients based on two independent inclusion criteria;1) patients with unspecific symptoms, i.e. fever (≥38.0℃) or a history of feverishness and/or any combination of headache, myalgia or arthralgia and 2) patients with erythema migrans (EM), following an observed tick bite or tick exposure within one month prior to onset of symptoms. A total of 206 patients fulfilled the study. Among these, we could identify 186 cases of LB (174 with EM), 18 confirmed and two probable cases of HGA and two cases of TBE. Thirteen of the HGA cases presented without fever. Furthermore, 22 of the EM patients had a sub-clinical co-infection with Anaplasma phagocytophilum, based on serology. Both TBE cases had co-infections, one with Borrelia burgdorferi and one with Anaplasma phagocytophilum. We conclude that it is important to consider several causative agents and possible co-infections in the clinical management of infectious diseases where ticks may be suspected as vectors.展开更多
Microbial stimulation in early childhood may be necessary for proper maturation of the immune system. Infants colonized with Staphylococcus aureus have low risk of developing food allergy. Neonatal exposure to staphyl...Microbial stimulation in early childhood may be necessary for proper maturation of the immune system. Infants colonized with Staphylococcus aureus have low risk of developing food allergy. Neonatal exposure to staphylococcal superantigen improves oral tolerance and enhances protection in experimental allergy models. Here, we used three wild-type strains of S. aureus, naturally harboring genes for different superantigens (SElM/SElO alone, or in combination with SEA or TSST-1). We first investigated their in vitro stimulatory capacity of splenocytes from germ-free mice. Secondly, germ-free mice were colonized with the strains and their capacity to develop oral tolerance was tested in a food allergy model. In vitro, S. aureus with only SElM/SElO genes promoted the strongest B-cell stimulation. S. aureus carrying gene for SEA induced the highest proportion of CD4<sup>+</sup>FoxP3<sup>+</sup> T cells. The proportion of regulatory T cells was inversely correlated to B-cell proliferation, indicating suppressive ability of these cells. All strains were equally able to colonize the germ-free gut, initially achieving 10<sup>10</sup>CFU/g faeces, which decreased to 10<sup>5</sup> over a period of six weeks. Mice colonized with S. aureus carrying genes for SEA or TSST-1 had improved capacity to develop tolerance compared to germ-free mice. These results suggest that colonization by S. aureus producing superantigens may improve active tolerance to gut allergens.展开更多
We expose a case of a woman with hypertension and hypokalemia. The differential diagnosis should include primary hyperaldosteronism, diuretics or lazantes intake, secondary hyperaldosteronism. In this patient, additio...We expose a case of a woman with hypertension and hypokalemia. The differential diagnosis should include primary hyperaldosteronism, diuretics or lazantes intake, secondary hyperaldosteronism. In this patient, additional tests performed show no cause of hormonal disruption and the whole picture is due to a high intake of licorice. Glycyrrhetinic acid, the active component of licorice, inhibits renal IIbeta-hydroxisteroid dehydrogenase. This allows cortisol to stimulate mineralocorticoid receptors. Licorice ingestion should be considered in the differential diagnosis of hypertension with hypokalemia.展开更多
The objective of this study was to examine longitudinally the effects of exenatide on different physical and biochemical markers, evaluated in adult type 2 diabetic patients with cardiovascular risk. Data were recorde...The objective of this study was to examine longitudinally the effects of exenatide on different physical and biochemical markers, evaluated in adult type 2 diabetic patients with cardiovascular risk. Data were recorded from 10 patients who attended the outpatient primary care health center Mariano Iago Yecla, Murcia province, Spain in the period of December 2009 to October 2011 and who were treated with Byetta®. Differences were statistically significant (p 0.05) in HbA1c from the third month of treatment, and trends of decrease in body weight from the third week of treatment. There was a significant and better glycemic control. Overall effect was interpreted as a sensitizer drug of the parameters evaluated. Randomized studies are recommended with a minimum follow-up of 2 years, to see if the results are maintained over time.展开更多
Patients with diabetes are characterized by the development of cardiovascular complications: nephropathy, retinopathy, neuropathy, ischemia or hypertensive etc. Therefore, the cardiovascular involvement is the leading...Patients with diabetes are characterized by the development of cardiovascular complications: nephropathy, retinopathy, neuropathy, ischemia or hypertensive etc. Therefore, the cardiovascular involvement is the leading cause of death in patients with Diabetes Mellitus type 2 (DM2). Despite intensive treatment on classical factors of cardiovascular disease (blood pressure levels, LDL cholesterol, etc.), patients with diabetes have a high number of cardiovascular events and the onset and prognosis of these are related to glycemic control parameters, glycosylated hemoglobin (HbA1c). On the other hand, the question of the cardiovascular protective effect of some hypoglycemic treatments has been raised, asking what he has done to know more accurately about the safety and cardiovascular effects of the treatments we have today. The two most important incretin hormones are GIP (gastric inhibitory polypeptide) and GLP-1 (glucagon-like peptide-1). Treatment based on GLP-1 is a novel weapon in T2DM that achieves a reduction in HbA1c with other metabolic effects: weight loss and extra effect in dyslipidemia and blood pressure. In the last years other beneficial actions such a protector effect against myocardium ischemia and other actions in basals were reported. In this article we will try to explain the evidence of GLP-1 treatments and its cardiovascular effects.展开更多
Worldwide, the prevalence of diabetes and obesity is increasing in recent years in developed countries. The first step of treatment is changes in lifestyle and in case of failure to initiate drug treatment. In our cas...Worldwide, the prevalence of diabetes and obesity is increasing in recent years in developed countries. The first step of treatment is changes in lifestyle and in case of failure to initiate drug treatment. In our case, the patient with morbid obesity and glucose intolerance to metformin therapy was initiated without achieving weight loss and loss of glycemic control after 6 months of treatment. It was decided to add exenatide as an alternative to bariatric surgery. At the end of the study (12 months), it showed a weight reduction of 20.8% (Table 1), 20.83% BMI, glycosylated hemoglobin decrease of 2 points, and improved the lipid profile. So exenatide may be an acceptable option in the use of patient profile. It would be necessary to seek a new alternative treatment with minimal side effects and less healthcare costs.展开更多
BACKGROUND Surgical site infections(SSIs)increase mortality,hospital stays,additional medical treatment,and medical costs.Subcutaneous drains prevent SSIs in gynecological and breast surgeries;however,their clinical i...BACKGROUND Surgical site infections(SSIs)increase mortality,hospital stays,additional medical treatment,and medical costs.Subcutaneous drains prevent SSIs in gynecological and breast surgeries;however,their clinical impact in abdominal surgery remains unclear.AIM To investigate whether subcutaneous drains were beneficial in abdominal surgery using a systematic review and meta-analysis.METHODS The database search used PubMed,MEDLINE,and the Cochrane Library.The following inclusion criteria were set for the systematic review:(1)Randomized controlled trial studies comparing SSIs after abdominal surgery with or without subcutaneous drains;and(2)Studies that described clinical outcomes,such as SSIs,seroma formation,the length of hospital stays,and mortality.RESULTS Eight studies were included in this meta-analysis.The rate of total SSIs was significantly lower in the drained group(54/771,7.0%)than in the control group(89/759,11.7%),particularly in gastrointestinal surgery.Furthermore,the rate of superficial SSIs was slightly lower in the drained group(31/517,6.0%)than in the control group(49/521,9.4%).No significant differences were observed in seroma formation between the groups.Hospital stays were shorter in the drained group than in the control group.CONCLUSION Subcutaneous drains after abdominal surgery prevented SSIs and reduced hospital stays but did not significantly affect seroma formation.The timing of drain removal needs to be reconsidered in future studies.展开更多
In the last decades we have witnessed a significant increase in the incidence of type 2 diabetes mellitus, and obesity in parallel. So 90% of patients with Diabetes Mellitus type 2 (DM2) are obese. Changes in lifestyl...In the last decades we have witnessed a significant increase in the incidence of type 2 diabetes mellitus, and obesity in parallel. So 90% of patients with Diabetes Mellitus type 2 (DM2) are obese. Changes in lifestyle (diet and exercise), behavioral therapies or the use of certain anti-obesity drugs have shown a limited effect and are not maintained over time. Currently, bariatric surgery is the most effective anti-obesity treatment, which is durable and resolves associated comorbidities. The surgical treatment of obesity for the modification of the anatomy of the digestive system is to produce gastric capacity constraints alone or associate with varying degrees of intestinal malabsorption and reduce body weight, improve and maintain the comorbidities associated weight loss by reduced food intake alone or in combination with malabsorption of this. The development of these surgical techniques has occurred in stages. With these techniques, setting to bariatric surgery is an effective, safe and proven procedure for the treatment of obesity and its complications especially DM2, as their post surgery referral mechanisms provide us with information for potential therapeutic treatment aimed at optimizing the control DM2 patients metabolic obese. In this review, we expose the evidence in treatment of DM2 with bariatric surgery and the actual hypothesis trying to explain how it is possible.展开更多
In a recent publication in Nature,Sakoguchi et al.reveal a long-sought missing link between pathogen-derived ligands and activating human natural killer(NK)cell receptors.1 The study identifies a clade of Plasmodium f...In a recent publication in Nature,Sakoguchi et al.reveal a long-sought missing link between pathogen-derived ligands and activating human natural killer(NK)cell receptors.1 The study identifies a clade of Plasmodium falciparum(P.falciparum)repetitive interspersed family(RIFIN)proteins that not only bind to the inhibitory KIR2DL1 receptor but,strikingly,also engage the activating KIR2DS1 receptor,thereby offering new insight into NK cell regulation in malaria and expanding our understanding of host–pathogen interaction in innate immune responses.展开更多
Objective:Stress is the main factor that leads to hair loss,and no effective therapeutics have been developed for stress alopecia.Polygonum multiflorum Thunb.(PM)is a famous traditional Chinese medicine for tonifying ...Objective:Stress is the main factor that leads to hair loss,and no effective therapeutics have been developed for stress alopecia.Polygonum multiflorum Thunb.(PM)is a famous traditional Chinese medicine for tonifying the kidney and nourishing the liver,which is used to treat hair loss.This study aimed to demonstrate that PM is a promising agent for the treatment of chronic stress-induced hair loss.Materials and Methods:C57BL/6J male mice were subjected to chronic restraint stress to inhibit hair follicle growth.Subsequently,the effect of PM was examined by oral administration of the PM water extract or cortisone,followed by histological analysis,immunofluorescence of follicle samples,serum metabolomics,and adrenal proteomics.Results:Hair regeneration in a mouse model was severely inhibited by chronic restraint stress.After PM treatment,hair regeneration in model mice was promoted,including an increased length of hair shafts in skin sections,an increased number of 5-Ethynyl-2'-deoxyuridine-positive cells,and a decreased number of apoptotic cells around the hair follicles.The various test indicators of these PM-treated mice almost recovered to levels comparable to those of the control mice.Through metabolomics and proteomics analyses,we identified 181 endogenous differential metabolites and 75 differential proteins,which may be the potential targets for PM.Pathway enrichment analysis showed that steroid biosynthesis(the main pathway through which stress leads to an imbalance in glucocorticoid secretion by the adrenal gland)may play an important role in the therapeutic effects of PM.In addition,omics analysis revealed that glycolysis/gluconeogenesis,pyruvate metabolism,lipid metabolism,and other glucocorticoid-related metabolic pathways differed significantly after PM treatment.Conclusions:PM is an important natural drug that regulates hair regeneration in mice under stress,and its underlying mechanism is closely related to the regulation of adrenal glucocorticoids and their metabolism.展开更多
Although the coronavirus disease 2019(COvID-19)pandemic has ended,the enduring health impacts of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection continue to garner global attention,as approximatel...Although the coronavirus disease 2019(COvID-19)pandemic has ended,the enduring health impacts of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection continue to garner global attention,as approximately 10%of patients develop long COVID(post COVID-19 condition).The epidemiological characteristics and symptoms of long COVID have been reported,and various pathogenic hypotheses have been proposed.Recent evidence suggests that SARS-CoV-2 nucleic acids or fragments persist in some patients post-infection and that these are correlated with long COvID symptoms.This review focuses on clinical studies linking SARS-CoV-2 persistence to long COVID symptoms,and explores the relationship between viral persistence and other etiological hypotheses,such as immune dysregulation,vascular issues,coagulation dysfunction,microbiome dysbiosis,brainstem/vagus nerve signaling dysfunction,and latent virus reactivation.Futhermore,treatment strategies for long COvID are proposed based on current clinical trials of antiviral and immune modulation therapies.Understanding the role of viral persistence in long COvID pathogenesis is critical for developing targeted therapies and improving clinical management of this debilitating condition.展开更多
China banned colistin as growth promoter for animals in the year of 2017.A decrease of colistin-resistant Escherichia coli(COREC)and mcr-1-positive Escherichia coli(MCRPEC)were observed in livestock(pigs and chickens)...China banned colistin as growth promoter for animals in the year of 2017.A decrease of colistin-resistant Escherichia coli(COREC)and mcr-1-positive Escherichia coli(MCRPEC)were observed in livestock(pigs and chickens)and humans after the ban policy.However,the prevalence of COREC among Chinese companion animals after the ban policy has not been investigated.Here,we recovered 771 E.coli isolates from the China Antimicrobial Resistance Surveil-lance Network for Pets(CARPet)surveillance system(19 provinces/municipalities)from 2018 to 2021.We identified 12 COREC from eight dogs and four cats,among which one feline and three canine isolates were MCRPEC.The prevalence of COREC and MCRPEC in pets from 2018-2021(1.1%-2.2%and 0.8%-1.1%)were lower than those from 2012-2016(7.1%-17.8%and 6.1%-14.3%).The phylogenetic analysis revealed that the four MCRPEC isolates displayed genetic diversity,while one canine isolate exhibited only 26 SNPs difference with one human MCRPEC isolate in the same city,suggesting the exchange of MCRPEC isolates between companion animals and humans.In three MCRPEC isolates,mcr-1 was located on an IncI2 plasmid,which exhibited 99.5%-99.9%nucleotide sequence identity with plasmid pHNSD133-MCR from E.coli of chicken origin.In the remaining MCRPEC,mcr-1 was chromosomally located flanked by intact ISApl1 elements forming a unit of ISApl1-mcr-1-pap2-ISApl1.Despite the low prevalence of COREC and MCRPEC observed in companion animals after the ban policy,the association of pet-derived MCRPEC and mcr-carrying plasmids with those from humans and farm animals suggest that annual surveillance of colistin resistance in bacteria of pet origin is essential.展开更多
Background and aims:Esophagogastric varices(EGV)are common complications of primary biliary cholangitis(PBC).We examined the risk factors for variceal bleeding-related liver transplantation(LT)or death.Methods:This pr...Background and aims:Esophagogastric varices(EGV)are common complications of primary biliary cholangitis(PBC).We examined the risk factors for variceal bleeding-related liver transplantation(LT)or death.Methods:This prospective observational cohort study involved PBC in our hospital from 1 January 2005 to 1 January 2020.The clinical endpoints were variceal bleeding-related LT and death.Survival analysis was performed using the Kaplan-Meier estimate,cox regression analysis was performed to investigate risk factors.Results:PBC with EGV had significantly shorter survival than those without(p?0.002).Endoscopic prophylaxis significantly improved poor outcomes in PBC with EGV(p<0.001).Risk factors in patients with EGV included:cholinesterase(CHE)of<1.0upper limit of normal(ULN),international normalized ratio(INR)of>1.2ULN at baseline,total bilirubin of>1.2ULN,aspartate aminotransferase(AST)of>2.3ULN after 1 year of ursodeoxycholic acid(UDCA)treatment,non-biochemical responders according to the Paris criteria,and no history of endoscopic therapy.In PBC without EGV,risk factors included AST of>2.3ULN,INR of>1.2ULN at baseline,CHE of<1.0ULN after 1 year of UDCA treatment,and GLOBE score of>1.125.Conclusion:This study provides evidence that AST,INR and CHE are major risk factors for variceal bleedingrelated poor outcomes in PBC.For PBC with EGV,a good biochemical response to UDCA and endoscopic prophylaxis may improve survival.These findings can aid for guiding initial PBC risk stratification and screening endoscopy in patients without EGV.展开更多
Allergic diseases have become a significant global health issue with prevalence rates increasing over recent decades[1].However,safe and long-lasting strategies to prevent or treat allergic disorders are still lacking...Allergic diseases have become a significant global health issue with prevalence rates increasing over recent decades[1].However,safe and long-lasting strategies to prevent or treat allergic disorders are still lacking,with the exception of active allergen avoidance,physical protective measures,or the intake of antihistamines upon accidental exposure.Recently,Rochman et al.reported the application of a lipid nanoparticle(LNP)-mRNA platform to develop anti-allergy vaccines[2],which coincided with our recent finding that ovalbumin(OVA)-mRNA-LNP and OVA-interleukin(IL)-10-mRNA-LNP vaccines demonstrate prophylactic efficacy against the onset of allergic responses[3].Both studies proposed that an allergen-specific mRNA vaccine could shift Th2-type allergic immunity to a Th1 phenotype,and concomitantly elicit robust levels of allergen-specific immunoglobulin G(IgG)that block the immunoglobulin E(IgE)-allergen interaction.However,the rationale for using unmodified whole allergens in vaccine development remains uncertain based on the potential risk of allergenicity.Additionally,it remains to be determined whether Th1-type T cell responses or allergen-blocking antibodies play a more pivotal role in mediating anti-allergic effects.展开更多
基金supported by the National Natural Science Foundation of China,No.81373020Beijing Natural Science Foundation of China,No.7112014+1 种基金a grant from the Science and Technology Development Project of Beijing Municipal Education Commission of China,No.KM201110025014a grant from the Beijing Municipal Science and Technology Project of China,No.Z131107002213071
文摘D-galactose has been widely used in aging research because of its efficacy in inducing senescence and accelerating aging in animal models. The present study investigated the benefits of exercise for preventing neurodegeneration, such as synaptic plasticity, spatial learning and memory abilities, in mouse models of aging. D-galactose-induced aging mice were administered daily subcutaneous injections of D-galactose at the base of the neck for 10 consecutive weeks. Then, the mice were subjected to exercise training by running on a treadmill for 6 days a week. Shortened escape latency in a Morris water maze test indicated that exercise improved learning and memory in aging mice. The ameliorative changes were likely induced by an upregulation of Bcl-2 and brain-derived neurotrophic factor, the repression of apoptosis factors such as Fas and Bax, and an increase in the activity of glucose transporters-1 and 4. The data suggest moderate exercise may retard or inhibit neurodegeneration in D-galactose-induced aging mice.
基金Open access funding provided by Karolinska Institute.
文摘Why neurogenesis is attenuated in elderly individuals is an intriguing question that has raised renewed interest.Mechanisms associated with declined neurogenesis in the aged brain have been attributed to inflammatory cytokines[1].More recently,a specific role for interferon-y(IFN-y)produced by CD8-expressing cytotoxic T cells has been implicated[2].These observations suggest a scenario in which neurogenesis,at least in part,is regulated by immune cells within the aging brain.This raises several interesting questions with regards to the characteristics of specific immune cells within the brain,the signals for their expansion and maintenance,and their role in affecting neurogenesis and cognition during normal brain aging.
基金Supported by the National Natural Science Foundation of China(No.20902009)the National Science Foundation for Post-Doctoral Scientists of China(Nos.2011M500051,2012T50258)+2 种基金the Yang Fan Scarce Top Talent Project of Guangdong Province(to ZHANG Yi)the Program for Scientific Research Start-up Funds of Guangdong Ocean University(GDOU)(to ZHANG Yi)the Natural Science Research Project of GDOU(No.C14519)
文摘Until recently, little was known about the fungi found in shark gills and their biomedicinal potential. In this article, we described the isolation, bioactivity, diversity, and secondary metabolites of bioactive fungi from the gill of a shark （Carcharodon carcharias）. A total of 115 isolates were obtained and grown in 12 culture media. Fifty-eight of these isolates demonstrated significant activity in four antimicrobial, pesticidal, and cytotoxic bioassay models. Four randomly selected bioactive isolates inhibited human cancer cell proliferation during re-screening. These active isolates were segregated into 6 genera using the internal transcribed spacer-large subunit （ITS-LSU） rDNA-sequence BLAST comparison. Four genera, Penicillium, Aspergillus, Mucor, and Chaetomium were the dominant taxa. A phylogenic tree illustrated their intergenera and intragenera genetic diversity. HPLC-DAD-HRMS analysis and subsequent database searching revealed that nine representative strains produced diverse bioactive compound profiles. These results detail the broad range of bioactive fimgi found in a shark＇s gills, revealing their biopharmaceutical potential. To the best of our knowledge, this is the first study characterizing shark gill fungi and their bioactivity.
基金the National Key Research and Development Program of China,No.2017YFC0908104National Science and Technology Projects,No.2017ZX10203201,No.2017ZX10201201,and No.2017ZX10202202.
文摘BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy options are still lacking.Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1(NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis,but its role in diseases including hepatic fibrosis remains undefined.Therefore,additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment.AIM To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1.METHODS Twenty-four male C57BL/6 mice were randomized and separated into three groups,comprising the normal,fibrosis,and calcitriol treatment groups,and liver fibrosis was modeled by carbon tetrachloride(CCl4).To evaluate the level of hepatic fibrosis in every group,serological and pathological examinations of the liver were conducted.TGF-β1 was administered to boost the in vitro cultivation of LX-2 cells.NS3TP1,α-smooth muscle actin(α-SMA),collagen I,and collagen Ⅲ in every group were examined using a Western blot and real-time quantitative polymerase chain reaction.The activity of the transforming growth factor beta 1(TGFβ1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected.The statistical analysis of the data was performed using the Student’s t test.RESULTS NS3TP1 promoted the activation,proliferation,and differentiation of hepatic stellate cells(HSCs)and enhanced hepatic fibrosis via the TGFβ1/Smad3 and NF-κB signaling pathways,as evidenced by the presence of α-SMA,collagen I,collagen Ⅲ,p-smad3,and p-p65 in LX-2 cells,which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference.The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression,as shown by the luciferase assay.NS3TP1 inhibited the apoptosis of HSCs.Moreover,both Smad3 and p65 could bind to NS3TP1,and p65 increased the promoter activity of NS3TP1,while NS3TP1 increased the promoter activity of TGFβ1 receptor I,as indicated by coimmunoprecipitation and luciferase assay results.Both in vivo and in vitro,treatment with calcitriol dramatically reduced the expression of NS3TP1.Calcitriol therapy-controlled HSCs activation,proliferation,and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice.Furthermore,calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1.CONCLUSION Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique,prospective therapeutic target in hepatic fibrosis.
基金FORSS—The Health Research Council in the Southeast of Sweden(Grant No 2000-320, 2001-332, 2002-335)research funds from the Ostergotland County Council (Grant No 2000-027, 2001-015, 2002-031)the Ostergotland County Council
文摘In Scandinavia, tick-borne infections affecting humans include Lyme borreliosis (LB), tick-borne encephalitis (TBE) and human granulocytic anaplasmosis (HGA). Each of these infections can present with unspecific symptoms. In this prospective clinical study, we recruited patients based on two independent inclusion criteria;1) patients with unspecific symptoms, i.e. fever (≥38.0℃) or a history of feverishness and/or any combination of headache, myalgia or arthralgia and 2) patients with erythema migrans (EM), following an observed tick bite or tick exposure within one month prior to onset of symptoms. A total of 206 patients fulfilled the study. Among these, we could identify 186 cases of LB (174 with EM), 18 confirmed and two probable cases of HGA and two cases of TBE. Thirteen of the HGA cases presented without fever. Furthermore, 22 of the EM patients had a sub-clinical co-infection with Anaplasma phagocytophilum, based on serology. Both TBE cases had co-infections, one with Borrelia burgdorferi and one with Anaplasma phagocytophilum. We conclude that it is important to consider several causative agents and possible co-infections in the clinical management of infectious diseases where ticks may be suspected as vectors.
文摘Microbial stimulation in early childhood may be necessary for proper maturation of the immune system. Infants colonized with Staphylococcus aureus have low risk of developing food allergy. Neonatal exposure to staphylococcal superantigen improves oral tolerance and enhances protection in experimental allergy models. Here, we used three wild-type strains of S. aureus, naturally harboring genes for different superantigens (SElM/SElO alone, or in combination with SEA or TSST-1). We first investigated their in vitro stimulatory capacity of splenocytes from germ-free mice. Secondly, germ-free mice were colonized with the strains and their capacity to develop oral tolerance was tested in a food allergy model. In vitro, S. aureus with only SElM/SElO genes promoted the strongest B-cell stimulation. S. aureus carrying gene for SEA induced the highest proportion of CD4<sup>+</sup>FoxP3<sup>+</sup> T cells. The proportion of regulatory T cells was inversely correlated to B-cell proliferation, indicating suppressive ability of these cells. All strains were equally able to colonize the germ-free gut, initially achieving 10<sup>10</sup>CFU/g faeces, which decreased to 10<sup>5</sup> over a period of six weeks. Mice colonized with S. aureus carrying genes for SEA or TSST-1 had improved capacity to develop tolerance compared to germ-free mice. These results suggest that colonization by S. aureus producing superantigens may improve active tolerance to gut allergens.
文摘We expose a case of a woman with hypertension and hypokalemia. The differential diagnosis should include primary hyperaldosteronism, diuretics or lazantes intake, secondary hyperaldosteronism. In this patient, additional tests performed show no cause of hormonal disruption and the whole picture is due to a high intake of licorice. Glycyrrhetinic acid, the active component of licorice, inhibits renal IIbeta-hydroxisteroid dehydrogenase. This allows cortisol to stimulate mineralocorticoid receptors. Licorice ingestion should be considered in the differential diagnosis of hypertension with hypokalemia.
文摘The objective of this study was to examine longitudinally the effects of exenatide on different physical and biochemical markers, evaluated in adult type 2 diabetic patients with cardiovascular risk. Data were recorded from 10 patients who attended the outpatient primary care health center Mariano Iago Yecla, Murcia province, Spain in the period of December 2009 to October 2011 and who were treated with Byetta®. Differences were statistically significant (p 0.05) in HbA1c from the third month of treatment, and trends of decrease in body weight from the third week of treatment. There was a significant and better glycemic control. Overall effect was interpreted as a sensitizer drug of the parameters evaluated. Randomized studies are recommended with a minimum follow-up of 2 years, to see if the results are maintained over time.
文摘Patients with diabetes are characterized by the development of cardiovascular complications: nephropathy, retinopathy, neuropathy, ischemia or hypertensive etc. Therefore, the cardiovascular involvement is the leading cause of death in patients with Diabetes Mellitus type 2 (DM2). Despite intensive treatment on classical factors of cardiovascular disease (blood pressure levels, LDL cholesterol, etc.), patients with diabetes have a high number of cardiovascular events and the onset and prognosis of these are related to glycemic control parameters, glycosylated hemoglobin (HbA1c). On the other hand, the question of the cardiovascular protective effect of some hypoglycemic treatments has been raised, asking what he has done to know more accurately about the safety and cardiovascular effects of the treatments we have today. The two most important incretin hormones are GIP (gastric inhibitory polypeptide) and GLP-1 (glucagon-like peptide-1). Treatment based on GLP-1 is a novel weapon in T2DM that achieves a reduction in HbA1c with other metabolic effects: weight loss and extra effect in dyslipidemia and blood pressure. In the last years other beneficial actions such a protector effect against myocardium ischemia and other actions in basals were reported. In this article we will try to explain the evidence of GLP-1 treatments and its cardiovascular effects.
文摘Worldwide, the prevalence of diabetes and obesity is increasing in recent years in developed countries. The first step of treatment is changes in lifestyle and in case of failure to initiate drug treatment. In our case, the patient with morbid obesity and glucose intolerance to metformin therapy was initiated without achieving weight loss and loss of glycemic control after 6 months of treatment. It was decided to add exenatide as an alternative to bariatric surgery. At the end of the study (12 months), it showed a weight reduction of 20.8% (Table 1), 20.83% BMI, glycosylated hemoglobin decrease of 2 points, and improved the lipid profile. So exenatide may be an acceptable option in the use of patient profile. It would be necessary to seek a new alternative treatment with minimal side effects and less healthcare costs.
基金Supported by Grants-in-Aid from JSPS KAKENHI,No.JP 21K10715 and No.JP 20K10404Northern Advancement Center for Science&Technology,No.T-2-2+9 种基金the Yasuda Medical Foundation,No.31010316the Okawa Foundation for Information and Telecommunications,No.41111042Taiju Life Social Welfare Foundation,No.50811490Japan Keirin Autorace Foundation,No.2023M-378Project Mirai Cancer Research Grants,No.31010269Takahashi Industrial and Economic Research Foundation,No.50411278Sapporo Doto Hospital,No.50311211Noguchi Hospital,No.40310551Doki-kai Tomakomai Hospital,No.40710739Tsuchida Hospital,No.50811478.
文摘BACKGROUND Surgical site infections(SSIs)increase mortality,hospital stays,additional medical treatment,and medical costs.Subcutaneous drains prevent SSIs in gynecological and breast surgeries;however,their clinical impact in abdominal surgery remains unclear.AIM To investigate whether subcutaneous drains were beneficial in abdominal surgery using a systematic review and meta-analysis.METHODS The database search used PubMed,MEDLINE,and the Cochrane Library.The following inclusion criteria were set for the systematic review:(1)Randomized controlled trial studies comparing SSIs after abdominal surgery with or without subcutaneous drains;and(2)Studies that described clinical outcomes,such as SSIs,seroma formation,the length of hospital stays,and mortality.RESULTS Eight studies were included in this meta-analysis.The rate of total SSIs was significantly lower in the drained group(54/771,7.0%)than in the control group(89/759,11.7%),particularly in gastrointestinal surgery.Furthermore,the rate of superficial SSIs was slightly lower in the drained group(31/517,6.0%)than in the control group(49/521,9.4%).No significant differences were observed in seroma formation between the groups.Hospital stays were shorter in the drained group than in the control group.CONCLUSION Subcutaneous drains after abdominal surgery prevented SSIs and reduced hospital stays but did not significantly affect seroma formation.The timing of drain removal needs to be reconsidered in future studies.
文摘In the last decades we have witnessed a significant increase in the incidence of type 2 diabetes mellitus, and obesity in parallel. So 90% of patients with Diabetes Mellitus type 2 (DM2) are obese. Changes in lifestyle (diet and exercise), behavioral therapies or the use of certain anti-obesity drugs have shown a limited effect and are not maintained over time. Currently, bariatric surgery is the most effective anti-obesity treatment, which is durable and resolves associated comorbidities. The surgical treatment of obesity for the modification of the anatomy of the digestive system is to produce gastric capacity constraints alone or associate with varying degrees of intestinal malabsorption and reduce body weight, improve and maintain the comorbidities associated weight loss by reduced food intake alone or in combination with malabsorption of this. The development of these surgical techniques has occurred in stages. With these techniques, setting to bariatric surgery is an effective, safe and proven procedure for the treatment of obesity and its complications especially DM2, as their post surgery referral mechanisms provide us with information for potential therapeutic treatment aimed at optimizing the control DM2 patients metabolic obese. In this review, we expose the evidence in treatment of DM2 with bariatric surgery and the actual hypothesis trying to explain how it is possible.
文摘In a recent publication in Nature,Sakoguchi et al.reveal a long-sought missing link between pathogen-derived ligands and activating human natural killer(NK)cell receptors.1 The study identifies a clade of Plasmodium falciparum(P.falciparum)repetitive interspersed family(RIFIN)proteins that not only bind to the inhibitory KIR2DL1 receptor but,strikingly,also engage the activating KIR2DS1 receptor,thereby offering new insight into NK cell regulation in malaria and expanding our understanding of host–pathogen interaction in innate immune responses.
基金supported by the National Natural Science Foundation of China(grant numbers 82074112 and 82004057)Beijing Science Foundation for Distinguished Young Scholars(grant number JQ21026)the Science Fund for Distinguished Young Scholars of the Capital Medical University(grant number 1220090104)。
文摘Objective:Stress is the main factor that leads to hair loss,and no effective therapeutics have been developed for stress alopecia.Polygonum multiflorum Thunb.(PM)is a famous traditional Chinese medicine for tonifying the kidney and nourishing the liver,which is used to treat hair loss.This study aimed to demonstrate that PM is a promising agent for the treatment of chronic stress-induced hair loss.Materials and Methods:C57BL/6J male mice were subjected to chronic restraint stress to inhibit hair follicle growth.Subsequently,the effect of PM was examined by oral administration of the PM water extract or cortisone,followed by histological analysis,immunofluorescence of follicle samples,serum metabolomics,and adrenal proteomics.Results:Hair regeneration in a mouse model was severely inhibited by chronic restraint stress.After PM treatment,hair regeneration in model mice was promoted,including an increased length of hair shafts in skin sections,an increased number of 5-Ethynyl-2'-deoxyuridine-positive cells,and a decreased number of apoptotic cells around the hair follicles.The various test indicators of these PM-treated mice almost recovered to levels comparable to those of the control mice.Through metabolomics and proteomics analyses,we identified 181 endogenous differential metabolites and 75 differential proteins,which may be the potential targets for PM.Pathway enrichment analysis showed that steroid biosynthesis(the main pathway through which stress leads to an imbalance in glucocorticoid secretion by the adrenal gland)may play an important role in the therapeutic effects of PM.In addition,omics analysis revealed that glycolysis/gluconeogenesis,pyruvate metabolism,lipid metabolism,and other glucocorticoid-related metabolic pathways differed significantly after PM treatment.Conclusions:PM is an important natural drug that regulates hair regeneration in mice under stress,and its underlying mechanism is closely related to the regulation of adrenal glucocorticoids and their metabolism.
基金supported by National Key Research and Development Program of China(2022YFC2304803).
文摘Although the coronavirus disease 2019(COvID-19)pandemic has ended,the enduring health impacts of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection continue to garner global attention,as approximately 10%of patients develop long COVID(post COVID-19 condition).The epidemiological characteristics and symptoms of long COVID have been reported,and various pathogenic hypotheses have been proposed.Recent evidence suggests that SARS-CoV-2 nucleic acids or fragments persist in some patients post-infection and that these are correlated with long COvID symptoms.This review focuses on clinical studies linking SARS-CoV-2 persistence to long COVID symptoms,and explores the relationship between viral persistence and other etiological hypotheses,such as immune dysregulation,vascular issues,coagulation dysfunction,microbiome dysbiosis,brainstem/vagus nerve signaling dysfunction,and latent virus reactivation.Futhermore,treatment strategies for long COvID are proposed based on current clinical trials of antiviral and immune modulation therapies.Understanding the role of viral persistence in long COvID pathogenesis is critical for developing targeted therapies and improving clinical management of this debilitating condition.
基金supported by the National Key Research and Development Program of China(2022YFD1800400)National Natural Science Foundation of China(32141002)Beijing Municipal Science and Technology Project(Z171100001517008).
文摘China banned colistin as growth promoter for animals in the year of 2017.A decrease of colistin-resistant Escherichia coli(COREC)and mcr-1-positive Escherichia coli(MCRPEC)were observed in livestock(pigs and chickens)and humans after the ban policy.However,the prevalence of COREC among Chinese companion animals after the ban policy has not been investigated.Here,we recovered 771 E.coli isolates from the China Antimicrobial Resistance Surveil-lance Network for Pets(CARPet)surveillance system(19 provinces/municipalities)from 2018 to 2021.We identified 12 COREC from eight dogs and four cats,among which one feline and three canine isolates were MCRPEC.The prevalence of COREC and MCRPEC in pets from 2018-2021(1.1%-2.2%and 0.8%-1.1%)were lower than those from 2012-2016(7.1%-17.8%and 6.1%-14.3%).The phylogenetic analysis revealed that the four MCRPEC isolates displayed genetic diversity,while one canine isolate exhibited only 26 SNPs difference with one human MCRPEC isolate in the same city,suggesting the exchange of MCRPEC isolates between companion animals and humans.In three MCRPEC isolates,mcr-1 was located on an IncI2 plasmid,which exhibited 99.5%-99.9%nucleotide sequence identity with plasmid pHNSD133-MCR from E.coli of chicken origin.In the remaining MCRPEC,mcr-1 was chromosomally located flanked by intact ISApl1 elements forming a unit of ISApl1-mcr-1-pap2-ISApl1.Despite the low prevalence of COREC and MCRPEC observed in companion animals after the ban policy,the association of pet-derived MCRPEC and mcr-carrying plasmids with those from humans and farm animals suggest that annual surveillance of colistin resistance in bacteria of pet origin is essential.
基金supported by the National Natural Science Foundation of China[Nos 82170538 and 81873564]the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine[No.ZYYCXTD-C-202005].
文摘Background and aims:Esophagogastric varices(EGV)are common complications of primary biliary cholangitis(PBC).We examined the risk factors for variceal bleeding-related liver transplantation(LT)or death.Methods:This prospective observational cohort study involved PBC in our hospital from 1 January 2005 to 1 January 2020.The clinical endpoints were variceal bleeding-related LT and death.Survival analysis was performed using the Kaplan-Meier estimate,cox regression analysis was performed to investigate risk factors.Results:PBC with EGV had significantly shorter survival than those without(p?0.002).Endoscopic prophylaxis significantly improved poor outcomes in PBC with EGV(p<0.001).Risk factors in patients with EGV included:cholinesterase(CHE)of<1.0upper limit of normal(ULN),international normalized ratio(INR)of>1.2ULN at baseline,total bilirubin of>1.2ULN,aspartate aminotransferase(AST)of>2.3ULN after 1 year of ursodeoxycholic acid(UDCA)treatment,non-biochemical responders according to the Paris criteria,and no history of endoscopic therapy.In PBC without EGV,risk factors included AST of>2.3ULN,INR of>1.2ULN at baseline,CHE of<1.0ULN after 1 year of UDCA treatment,and GLOBE score of>1.125.Conclusion:This study provides evidence that AST,INR and CHE are major risk factors for variceal bleedingrelated poor outcomes in PBC.For PBC with EGV,a good biochemical response to UDCA and endoscopic prophylaxis may improve survival.These findings can aid for guiding initial PBC risk stratification and screening endoscopy in patients without EGV.
文摘Allergic diseases have become a significant global health issue with prevalence rates increasing over recent decades[1].However,safe and long-lasting strategies to prevent or treat allergic disorders are still lacking,with the exception of active allergen avoidance,physical protective measures,or the intake of antihistamines upon accidental exposure.Recently,Rochman et al.reported the application of a lipid nanoparticle(LNP)-mRNA platform to develop anti-allergy vaccines[2],which coincided with our recent finding that ovalbumin(OVA)-mRNA-LNP and OVA-interleukin(IL)-10-mRNA-LNP vaccines demonstrate prophylactic efficacy against the onset of allergic responses[3].Both studies proposed that an allergen-specific mRNA vaccine could shift Th2-type allergic immunity to a Th1 phenotype,and concomitantly elicit robust levels of allergen-specific immunoglobulin G(IgG)that block the immunoglobulin E(IgE)-allergen interaction.However,the rationale for using unmodified whole allergens in vaccine development remains uncertain based on the potential risk of allergenicity.Additionally,it remains to be determined whether Th1-type T cell responses or allergen-blocking antibodies play a more pivotal role in mediating anti-allergic effects.
