Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains elusive.Prohibitin-2(PHB2)is a newly discove red autophagy receptor in the m...Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains elusive.Prohibitin-2(PHB2)is a newly discove red autophagy receptor in the mitochondrial inner membrane,and its role in Parkinson’s disease remains unclear.Protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)is a factor that regulates cell fate during endoplasmic reticulum stress.Parkin is regulated by PERK and is a target of the unfolded protein response.It is unclear whether PERK regulates PHB2-mediated mitophagy thro ugh Parkin.In this study,we established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of Parkinson’s disease.We used adeno-associated virus to knockdown PHB2 expression.Our res ults showed that loss of dopaminergic neurons and motor deficits were aggravated in the MPTP-induced mouse model of Parkinson’s disease.Ove rexpression of PHB2 inhibited these abnormalities.We also established a 1-methyl-4-phenylpyridine(MPP+)-induced SH-SY5Y cell model of Parkinson’s disease.We found that ove rexpression of Parkin increased co-localization of PHB2 and microtubule-associated protein 1 light chain 3,and promoted mitophagy.In addition,MPP+regulated Parkin involvement in PHB2-mediated mitophagy through phosphorylation of PERK.These findings suggest that PHB2 participates in the development of Parkinson’s disease by intera cting with endoplasmic reticulum stress and Parkin.展开更多
Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is k...Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°C.We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort.Plasma samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline project.These samples were stored at-80°C for up to 6 years before being used in this study.Our results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage time.However,the level of total tau showed a negative correlation with sample storage time.Notably,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage time.This was not observed in individuals with cognitive impairment.Consequently,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time.Therefore,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's disease.Furthermore,in cohort studies,it is important to consider the impact of storage time on the overall results.展开更多
Newcastle disease (ND) virus is a leading threat to commercial and domestic poultry in Pakistan. The virus infects and constitutes irreversible impairment to the nervous system, damages the respiratory system, and mar...Newcastle disease (ND) virus is a leading threat to commercial and domestic poultry in Pakistan. The virus infects and constitutes irreversible impairment to the nervous system, damages the respiratory system, and marks severe gastrointestinal lesions leading to heavy mortality in short-living birds and substantial losses in layers and breeders. The continuous emergence and evolution of the virus made it inclined to evade the humoral response and indirectly the circumvention of artificial active immunization. Newcastle disease is caused by the orthoavula genus of the paramyxoviridae family and has shown high genetic diversity even in their genotypes while information regarding enzootic trends of the virus is scanty in Pakistan. A total of 40 tracheal samples of NDV were collected from different commercial broiler farms and 11 isolates of NDV were identified. In the current study, we determined the genetic diversity of the Newcastle disease virus based on the partial sequencing of the fusion protein gene available in the NCBI database. Genetic analysis showed that seven isolates belonged to class I genotype VII and four belonged to class II genotype II. Interestingly, two isolates had epidemiological connections with vaccine-like class II genotype II. Our findings, concerning the recent outbreaks of class I genotype VII and class II genotype II of NDV in vaccinated commercial flocks, suggest possible potential partial mutations in the fusion protein gene. Genetic diversity and formation of the new cleavage site in an important neutralizing protein of wild strain are linked with the potency of artificial active immunization and a major cause of vaccine failure.展开更多
Branched chain amino acids(BCAAs)have been shown to affect gene expression,protein metabolism,apoptosis and regeneration of hepatocytes,and insulin resistance.They have also been shown to inhibit the proliferation of ...Branched chain amino acids(BCAAs)have been shown to affect gene expression,protein metabolism,apoptosis and regeneration of hepatocytes,and insulin resistance.They have also been shown to inhibit the proliferation of liver cancer cells in vitro,and are essential for lymphocyte proliferation and dendritic cell maturation.In patients with advanced chronic liver disease,BCAA concentrations are low,whereas the concentrations of aromatic amino acids such as phenylalanine and tyrosine are high,conditions that may be closely associated with hepatic encephalopathy and the prognosis of these patients.Based on these basic observations,patients with advanced chronic liver disease have been treated clinically with BCAA-rich medicines,with positive effects.展开更多
BACKGROUND An altered (dysbiosis) and unhealthy status of the gut microbiota is usually responsible for a reduction of short chain fatty acids (SCFAs) concentration. SCFAs obtained from the carbohydrate fermentation p...BACKGROUND An altered (dysbiosis) and unhealthy status of the gut microbiota is usually responsible for a reduction of short chain fatty acids (SCFAs) concentration. SCFAs obtained from the carbohydrate fermentation processes are crucial in maintaining gut homeostasis and their determination in stool samples could provide a faster, reliable and cheaper method to highlight the presence of an intestinal dysbiosis and a biomarker for various gut diseases. We hypothesize that different intestinal diseases, such as celiac disease (CD), adenomatous polyposis (AP) and colorectal cancer (CRC) could display a particular fecal SCFAs’ signature. AIM To compare the fecal SCFAs’ profiles of CD, AP, CRC patients and healthy controls, using the same analytical method. METHODS In this cross-sectional study, we defined and compared the SCFAs’ concentration in fecal samples of 9 AP, 16 CD, 19 CRC patients and 16 healthy controls (HC). The SCFAs’ analysis were performed using a gas-chromatography coupled with mass spectrometry method. Data analysis was carried out using Wilcoxon ranksum test to assess pairwise differences of SCFAs’ profiles, partial least squaresdiscriminate analysis (PLS-DA) to determine the status membership based on distinct SCFAs’ profiles, and Dirichlet regression to determine factors influencing concentration levels of SCFAs. RESULTS We have not observed any difference in the SCFAs’ amount and composition between CD and healthy control. On the contrary, the total amount of SCFAs was significantly lower in CRC patients compared to HC (P = 0.044) and CD (P = 0.005). Moreover, the SCFAs’ percentage composition was different in CRC and AP compared to HC. In detail, HC displayed higher percentage of acetic acid (P value = 1.3 × 10-6) and a lower amount of butyric (P value = 0.02192), isobutyric (P value = 7.4 × 10-5), isovaleric (P value = 0.00012) and valeric (P value = 0.00014) acids compared to CRC patients. AP showed a lower abundance of acetic acid (P value = 0.00062) and higher percentages of propionic (P value = 0.00433) and isovaleric (P value = 0.00433) acids compared to HC. Moreover, AP showed higher levels of propionic acid (P value = 0.03251) and a lower level of isobutyric acid (P value = 0.00427) in comparison to CRC. The PLS-DA model demonstrated a significant separation of CRC and AP groups from HC, although some degree of overlap was observed between CRC and AP. CONCLUSION Analysis of fecal SCFAs shows the potential to provide a non-invasive means of diagnosis to detect patients with CRC and AP, while CD patients cannot be discriminated from healthy subjects.展开更多
This paper first applies the sequential cluster method to set up the classification standard of infectious disease incidence state based on the fact that there are many uncertainty characteristics in the incidence cou...This paper first applies the sequential cluster method to set up the classification standard of infectious disease incidence state based on the fact that there are many uncertainty characteristics in the incidence course.Then the paper presents a weighted Markov chain,a method which is used to predict the future incidence state.This method assumes the standardized self-coefficients as weights based on the special characteristics of infectious disease incidence being a dependent stochastic variable.It also analyzes the characteristics of infectious diseases incidence via the Markov chain Monte Carlo method to make the long-term benefit of decision optimal.Our method is successfully validated using existing incidents data of infectious diseases in Jiangsu Province.In summation,this paper proposes ways to improve the accuracy of the weighted Markov chain,specifically in the field of infection epidemiology.展开更多
Objective To establish a multiplex polymerase chain reaction (M-PCR) assay for simultaneous detection of pathogens causing genital ulcer disease (GUD). Mothods Based on the gene-specific region of the following p...Objective To establish a multiplex polymerase chain reaction (M-PCR) assay for simultaneous detection of pathogens causing genital ulcer disease (GUD). Mothods Based on the gene-specific region of the following pathogens: Chlamydia trachomatis omp l/ompb, herpes simplex virus (HSV) DNA polymerase, Treponema pollidum tpp47, Haemophilus ducreyi 16s rRNA, four sets of primers were designed and an M-PCR assay was developed to detect four pathogens in one test. The assay was evaluated with diagnostic result of golden standard for each pathogen.Results Of the 51 clinical samples, M-PCR showed slightly higher positive rate (47.1%) of HSV than cell culture (23.6%). Meanwhile, the positive rate of T. pallidum detected by M-PCR and dark-field microscopy was 19.6% (10/51) and 15.7% (8/51), respectively. Only one sample was positive for H. ducreyi and no sample was positive for C. trachomatis detected by both M-PCR assay and culture. Conclusion This primary study indicated that M-PCR assay can simultaneously and rapidly detect the four etiologic pathogens causing GUD.展开更多
The present paper reports 11 cases of light chain disease (LCD) sequently found in several citles over Fujian province, Immunological classification of this group of LCD ww as follows: six of me cases belonged to type...The present paper reports 11 cases of light chain disease (LCD) sequently found in several citles over Fujian province, Immunological classification of this group of LCD ww as follows: six of me cases belonged to type λ, four of them were type κ, and another one was a double LCD. We found that LCD was common in Fujlan only next to multiple myeloma (MM) of IgG class and accounted for 20% of the total 55 MM cases found in recent yean.It to well known that In matt patients of LCD M protein or Bence Jones proteinemia (BJPemia) to not detectable by conventional electro-phoresis. Our studies show that by making serum protein along with urinary BJP electrophoresis on the same one gel plate the sltuation can be greatly Improved It not only favour* the recognition of smail and faint band or bands of free light chain in serum, but also provides a repid and sensitive way, i. e. , immunofixation, to directly detect urinary light chain on the gel plate Immediately after electrophresis has been run.展开更多
Intracranial delivery of human Fc-deleted antibody specific to amyloid-β peptide (Aβ, anti-Aβ single-chain Fv, scFv) via adeno-associated virus (AAV) inhibits amyloid deposition in transgenic mice. However, the...Intracranial delivery of human Fc-deleted antibody specific to amyloid-β peptide (Aβ, anti-Aβ single-chain Fv, scFv) via adeno-associated virus (AAV) inhibits amyloid deposition in transgenic mice. However, the effects of AAV-mediated Fc-deleted antibody on animal behavior remain unclear. In this study, the anti-Aβ scFv antibody gone, isolated from phage display, was fused to the 5' end of the scFv antibody gone for antibody secretion by 2 rounds of polymerase chain reaction amplification. The fused antibody cDNA was cloned into a pSNAV2 plasmid under the control of the cytomegalovirus promoter. The sequence verified expression vector pSNAV2/scFv was transferred to BHK-21 ceils, and stable transfected BHK-21/scFv cells were established by G418 selection and infected with the recombinant herpes simplex virus rHSV/repcap for AAV production. Recombinant AAV was injected into the left quadriceps femoris of PDAPP transgenic mice. After 3 months, Morris water-maze results confirmed significantly improved cognitive function in a mouse model of Alzheimer's disease. Key Words: Alzheimer's disease; adeno-associated virus; amyloid-β peptide; single-chain antibody; neurodegenerative diseases; neural regeneration展开更多
Very long chain fatty acids (VLCFAs) are accumulated in cells and blood in patients with peroxisomal diseases, such as adrenoleukodystrophy (ALD) and Zellwger Syndrome (ZS). The purpose of this study is to investigate...Very long chain fatty acids (VLCFAs) are accumulated in cells and blood in patients with peroxisomal diseases, such as adrenoleukodystrophy (ALD) and Zellwger Syndrome (ZS). The purpose of this study is to investigate usefulness of Fourier transform infrared spectroscopy (FTIR) with attenuated total reflection (ATR) analysis method for clinical diagnosis of those diseases, thereby we measured the infrared spectra of the sera of patients and healthy controls. Correlation coefficients between 2nd derivative FTIR spectra of the serum samples and the VLCFA content ratio which is used as a clinical parameter to date were comprehensively calculated to investigate which wavenumber showed high correlation with the VLCFA ratio. Multiple regression analysis using the serum FTIR spectra showed that high correlations were observed with VLCFA ratios (C26:0/C22:0 ratio), and we could construct a suitable regression model (R2 = 0.97, p ﹣19). In addition, the model system using various VLCFAs in newborn bovine serum also showed that several FTIR peaks in 800 ~ 900 cm﹣1 region were found to have good correlation with VLCFA ratios. Our results support that FTIR analysis is useful for diagnosis of peroxisomal diseases.展开更多
IgG Heavy Chain Disease (γHCD) is a rare plasma cell disorder. Hypercalcemia related to plasma cell dyscrasias is related to non-PTHrP related mechanisms. Here we describe the first case of a patient with γHCD and P...IgG Heavy Chain Disease (γHCD) is a rare plasma cell disorder. Hypercalcemia related to plasma cell dyscrasias is related to non-PTHrP related mechanisms. Here we describe the first case of a patient with γHCD and PTHrP related hypercalcemia. Methods: Patient case derived from chart review from 2011 to 2015. Literature review performed searching PubMed 1968-current. Results: The patient was diagnosed with hypercalcemia with elevated PTHrP and exclusion of other etiologies of hypercalcemia. She was diagnosed with (γHCD) by M-spike 0.64 g/dL, IFE showing a broad band of IgG heavy chain, without associated light chains and severe depression of the non-mono-clonal IgG. Serum immunoglobulins demonstrated elevated IgG (2110 mg/dL), normal IgA (46 mg/dL) and decreased IgM (<21 mg/dL). Bone marrow biopsy showed 5% PCs, non-clonal by kappa/lambda, but exclusive for IgG by IHC, without any staining for IgA or IgM. The patient was started on therapy with improved hypercalcemia and PTHrP levels. Conclusions: This is the first reported case of γHCD presenting with PTHrP related hypercalcemia. Given that skeletal involvement is uncommon in γHCD, hypercalcemia secondary to γHCD may at times be a PTHrP driven phenomenon and we recommend that this test be ordered in such cases.展开更多
Oxidative stress and mitochondrial damage have been implicated in the pathogenesis of several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Oxidati...Oxidative stress and mitochondrial damage have been implicated in the pathogenesis of several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Oxidative stress is characterized by the overproduction of reactive oxygen species, which can induce mitochondrial DNA mutations, damage the mitochondrial respiratory chain, alter membrane permeability, and influence Ca2+ homeostasis and mitochondrial defense systems. All these changes are implicated in the development of these neurodegenerative diseases, mediating or amplifying neuronal dysfunction and triggering neurodegeneration. This paper summarizes the contribution of oxidative stress and mitochondrial damage to the onset of neurodegenerative diseases and discusses strategies to modify mitochondrial dysfunction that may be attractive therapeutic interventions for the treatment of various neurodegenerative diseases.展开更多
AIM: To compare the histopathologic features of intestinal tuberculosis (ITB) and Crohn’s disease (CD) and to identify whether polymerase chain reaction for Mycobacterium tuberculosis (TB-PCR) would be helpful for di...AIM: To compare the histopathologic features of intestinal tuberculosis (ITB) and Crohn’s disease (CD) and to identify whether polymerase chain reaction for Mycobacterium tuberculosis (TB-PCR) would be helpful for differential diagnosis between ITB and CD.METHODS: We selected 97 patients with established diagnoses (55 cases of ITB and 42 cases of CD) who underwent colonoscopic biopsies.Microscopic features of ITB and CD were reviewed,and eight pathologic parameters were evaluated.Nine cases of acid fast bacilli culture-positive specimens and 10 normal colonic tissue specimens were evaluated as the positive and negative control of the TB-PCR test,respectively.PCR assays were done using two commercial kits: kit <A> detected IS6110 and MPB64,and kit <B> detected IS6110 only;a manual in-house PCR method was also performed on formalin-fi xed,paraffi n-embedded colonoscopic biopsy specimens.RESULTS: Statistically significant differences were noted between ITB and CD with regard histopathologic criteria: size of granulomas (P = 0.000),giant cells (P = 0.015),caseation necrosis (P = 0.003),confluent granulomas (P = 0.001),discrete granulomas (P = 0.000),and granulomas with lymphoid cuffs (P = 0.037).However,29 cases (52.7%) of ITB showed less than fi ve kinds of pathologic parameters,resulting in confusion with CD.The sensitivities and specificities of the TB-PCR test by kit <A>,kit <B>,and the in-house PCR method were 88.9% and 100%,88.9% and 100%,and 66.7% and 100% in positive and negative controls,respectively.The PCR test done on endoscopic biopsy specimens of ITB and CD were signifi cantly different with kit <A> (P = 0.000) and kit <B> (P = 0.000).The sensitivities and specifi cities of TB-PCR were 45.5% and 88.1%,36.4% and 100%,and 5.8% and 100%,for kit <A> and kit <B> and inhouse PCR method on endoscopic biopsy specimens.Among the 29 cases of histopathologically confusing CD,10 cases assayed using kit <A> and 6 cases assayed using kit <B> were TB-PCR positive.A combination of histologic fi ndings and TB-PCR testing led to an increase of diagnostic sensitivity and the increase (from 47.3% to 58.2) was statistically signifi cant with kit <B> (P = 0.000).CONCLUSION: The TB-PCR test combined with histopathologic factors appears to be a helpful technique in formulating the differential diagnosis of ITB and CD in endoscopic biopsy samples.展开更多
Cytomegalovirus(CMV) infection is common in humans.The virus then enters a "latency phase" and can reactivate to different stimuli such as immunosuppression.The clinical significance of CMV infection in infl...Cytomegalovirus(CMV) infection is common in humans.The virus then enters a "latency phase" and can reactivate to different stimuli such as immunosuppression.The clinical significance of CMV infection in inflammatory bowel disease is different in Crohn's disease(CD) and ulcerative colitis(UC).CMV does not interfere in the clinical course of CD.However,CMV reactivation is frequent in severe or steroid-resistant UC.It is not known whether the virus exacerbates the disease or simply appears as a bystander of a severe disease.Different methods are used to diagnose CMV colitis.Diagnosis is classically based on histopathological identification of viral-infected cells or CMV antigens in biopsied tissues using haematoxylin-eosin or immunohistochemistry,other tests on blood or tissue samples are currently being investigated.Polymerase chain reaction performed in colonic mucosa has a high sensitivity and a positive result could be associated with a worse prognosis disease;further studies are needed to determine the most appropriate strategy with positive CMV-DNA in colonic mucosa.Specific endoscopic features have not been described in active UC and CMV infection.CMV colitis is usually treated with ganciclovir for several weeks,there are different opinions about whether or not to stop immunosuppressive therapy.Other antiviral drugs may be used.Multicenter controlled studies would needed to determine which subgroup of UC patients would benefit from early antiviral treatment.展开更多
INTRODUCTIONAlthough several specific detecting methods hadbeen applied to determine the hepatitis virus,therewas a lot of cryptogenic hepatitis without anyknown hepatitis infectious marker.Theprevalence of hepatitis ...INTRODUCTIONAlthough several specific detecting methods hadbeen applied to determine the hepatitis virus,therewas a lot of cryptogenic hepatitis without anyknown hepatitis infectious marker.Theprevalence of hepatitis G virus (HGV) (also knownas GB-C virus) infection has been reported to be 5%-13% in patients with non-A-E hepatitis andcirrhosis,however,there is little evidencesuggesting that HGV causes hepatitis in human.展开更多
AIM:To examine the detection rate of viable Mycobacterium avium subspecies paratuberculosis(MAP) in patients with inflammatory bowel disease [Crohn's disease(CD) and ulcerative colitis(UC)].METHODS:Thirty patients...AIM:To examine the detection rate of viable Mycobacterium avium subspecies paratuberculosis(MAP) in patients with inflammatory bowel disease [Crohn's disease(CD) and ulcerative colitis(UC)].METHODS:Thirty patients with CD(15 with at least one NOD2/CARD15 mutation),29 with UC,and 10 with no inflammatory bowel disease(IBD).were tested for MAP by polymerase chain reaction(specific IS900 fragment) and blood culture.RESULTS:MAP DNA was detected in all original blood samples and 8-wk blood cultures(CD,UC and non-IBD).Positive MAP DNA status was confirmed by dot blot assays.All 69 cultures were negative by acid-fast Ziehl-Neelsen staining.Viable MAP,in spheroplast form,was isolated from the 18-mo blood cultures of all 30 CD patients,one UC patient,and none of the non-IBD controls.No association was found between positive MAP cultures and use of immunosuppressive drugs or CDassociated single nucleotide polymorphisms.CONCLUSION:MAP is widely present in our area and MAP DNA can be recovered from the blood of CD,UC and non-IBD patients.However,MAP spheroplasts were only found in CD patients.展开更多
Mitochondria are one of the major sites for the genera-tion of reactive oxygen species(ROS) as an undesirable side product of oxidative energy metabolism. Damaged mitochondria can augment the generation of ROS. Dys-fu...Mitochondria are one of the major sites for the genera-tion of reactive oxygen species(ROS) as an undesirable side product of oxidative energy metabolism. Damaged mitochondria can augment the generation of ROS. Dys-function of mitochondria increase the risk for a large number of human diseases, including cardiovascular diseases(CVDs). Heart failure(HF) following ischemic heart disease, infantile cardiomyopathy and cardiac hypertrophy associated with left ventricular dilations are some of the CVDs in which the role of mitochon-drial oxidative stress has been reported. Advances in mitochondrial research during the last decade focused on the preservation of its function in the myocardium, which is vital for the cellular energy production. Expe-rimental and clinical trials have been conducted using mitochondria-targeted molecules like: MnSOD mimetics, such as EUK-8, EUK-134 and MitoSOD; choline esters of glutathione and N-acetyl-L-cysteine; triphenylphospho-nium ligated vitamin E, lipoic acid, plastoquinone andmitoCoQ10; and Szeto-Schiller(SS)- peptides(SS-02 and SS-31). Although many results are inconclusive, some of the findings, especially on CoQ10, are worthwhile. This review summarizes the role of mitochondria-tar-geted delivery of agents and their consequences in the control of HF.展开更多
Defects in autophagy-mediated clearance of α-synuclein may be one of the key factors leading to progressive loss of dopaminergic neurons in the substantia nigra. Moxibustion therapy for Parkinson’s disease has been ...Defects in autophagy-mediated clearance of α-synuclein may be one of the key factors leading to progressive loss of dopaminergic neurons in the substantia nigra. Moxibustion therapy for Parkinson’s disease has been shown to have a positive effect, but the underlying mechanism remains unknown. Based on this, we explored whether moxibustion could protect dopaminergic neurons by promoting autophagy mediated by mammalian target of rapamycin (mTOR), with subsequent elimination of α-syn. A Parkinson’s disease model was induced in rats by subcutaneous injection of rotenone at the back of their necks, and they received moxibustion at Zusanli (ST36), Guanyuan (CV4)and Fengfu (GV16), for 10 minutes at every point, once per day, for 14 consecutive days. Model rats without any treatment were used as a sham control. Compared with the Parkinson’s disease group, the moxibustion group showed significantly greater tyrosine hydroxylase immunoreactivity and expression of light chain 3-II protein in the substantia nigra, and their behavioral score, α-synuclein immunoreactivity,the expression of phosphorylated mTOR and phosphorylated ribosomal protein S6 kinase (p-p70S6K) in the substantia nigra were significantly lower. These results suggest that moxibustion can promote the autophagic clearance of α-syn and improve behavioral performance in Parkinson’s disease model rats. The protective mechanism may be associated with suppression of the mTOR/p70S6K pathway.展开更多
Here,we report a case of fulminant gastrointestinal graft-versus-host disease(GI-GVHD) with cytomegalovirus(CMV) infection in 44-year-old woman.Despite the difficulties associated with the treatment of GIGVHD and GI-C...Here,we report a case of fulminant gastrointestinal graft-versus-host disease(GI-GVHD) with cytomegalovirus(CMV) infection in 44-year-old woman.Despite the difficulties associated with the treatment of GIGVHD and GI-CMV disease,the mucosal findings and the clinical course showed marked improvements during long-term clinical observation.The endoscopic findings were remarkable,with diffuse sloughing mucosa in the stomach and highly active inflammation and deep discrete ulcers throughout the colon.Changes in the CMV quantitative polymerase chain reaction results were correlated with the endoscopic mucosal findings and were useful for assessing the efficacy of the treatment.Although a definite diagnosis of GI-GVHD is generally made by endoscopy with biopsy,the gross appearance of this disease can vary depending on the endoscopy.In this paper,we also conduct a literature review of patients with GI-GVHD.展开更多
AIM:To define the parameters that positively predict diagnosis of Crohn's disease (CD) and differentiate it from gastrointestinal tuberculosis (GITB). METHODS:This prospective study over 3 years was carried out in...AIM:To define the parameters that positively predict diagnosis of Crohn's disease (CD) and differentiate it from gastrointestinal tuberculosis (GITB). METHODS:This prospective study over 3 years was carried out in the consecutive Indian patients with definite diagnosis of CD and equal numbers of patients with definite diagnosis of GITB. Demographic, clinical, laboratory, morphological and histological features were noted in all the patients. Serological tests such as p-ANCA, c-ANCA, IgA ASCA and IgG ASCA, were performed. Endoscopic biopsy and/or surgical tissue specimens were subjected to smear and culture for acid-fast bacilli (AFB) and tissue polymerase chain reaction for tuberculosis (TB PCR). Diagnosis of CD and GITB was based on the standard criteria. Data were analyzed using univariate Chi-square test and multiple logistic regression (MLR). RESULTS:The study is comprised of 26 patients with CD (age 36.6 ± 8.6 year, male:female, 16:10) and 26 patients with GITB (age 37.2 ± 9.6 year, male:female, 15:11). The following clinical variables between the two groups (CD vs TB) were significant in univariate analysis:duration of symptoms (58.1 ± 9.8 vs 7.2 ± 3.4 mo), diarrhoea (69.2% vs 34.6%), bleeding per rectum (30.7% vs 3.8%), fever (23.1% vs 69.2%), ascites (7.7% vs 34.6%) and extra-intestinal manifestations of inflammatory bowel disease (61.5% vs 23.1%). Of these, all except ascites and extra-colonic manifestations were found statistically significant by MLR. Accuracy of predicting CD was 84.62% based on the fever, bleeding P/R, diarrhoea and duration of symptoms while it was 63.4% when histology was reported as inflammatory bowel disease and 42.3% when there was recurrence of disease after surgery. Accuracy of predicting GITB was 73.1% when there was co-existing pulmonary lesions and/or abdominal lymphadenopathy;75% when tuberculosis was reported in histology;63.4% when granuloma was found in histology;82.6% when TB PCR was positive;and 61.5% when smear and/ or culture was positive for AFB. Serological test was not useful in differentiation of CD from GITB. Positivity rates for CD and GITB were:p-ANCA-3.8% and 3.8%, c-ANCA-3.8% and 0%, IgA ASCA-38.4% and 23.1%, and IgG ASCA-38.4% and 42.3%, respectively. CONCLUSION:Simple clinical parameters like fever, bleeding P/R, diarrhoea and duration of symptoms have the highest accuracy in differentiating CD from GITB.展开更多
基金supported by the Key Science and Technology Research of Henan Province,No.222102310351(to JW)Luoyang 2022 Medical and Health Guiding Science and Technology Plan Project,No.2022057Y(to JY)Henan Medical Science and Technology Research Program Province-Ministry Co-sponsorship,No.SBGJ202002099(to JY)。
文摘Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains elusive.Prohibitin-2(PHB2)is a newly discove red autophagy receptor in the mitochondrial inner membrane,and its role in Parkinson’s disease remains unclear.Protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)is a factor that regulates cell fate during endoplasmic reticulum stress.Parkin is regulated by PERK and is a target of the unfolded protein response.It is unclear whether PERK regulates PHB2-mediated mitophagy thro ugh Parkin.In this study,we established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of Parkinson’s disease.We used adeno-associated virus to knockdown PHB2 expression.Our res ults showed that loss of dopaminergic neurons and motor deficits were aggravated in the MPTP-induced mouse model of Parkinson’s disease.Ove rexpression of PHB2 inhibited these abnormalities.We also established a 1-methyl-4-phenylpyridine(MPP+)-induced SH-SY5Y cell model of Parkinson’s disease.We found that ove rexpression of Parkin increased co-localization of PHB2 and microtubule-associated protein 1 light chain 3,and promoted mitophagy.In addition,MPP+regulated Parkin involvement in PHB2-mediated mitophagy through phosphorylation of PERK.These findings suggest that PHB2 participates in the development of Parkinson’s disease by intera cting with endoplasmic reticulum stress and Parkin.
基金supported by the National Key Research&Development Program of China,Nos.2021YFC2501205(to YC),2022YFC24069004(to JL)the STI2030-Major Project,Nos.2021ZD0201101(to YC),2022ZD0211800(to YH)+2 种基金the National Natural Science Foundation of China(Major International Joint Research Project),No.82020108013(to YH)the Sino-German Center for Research Promotion,No.M-0759(to YH)a grant from Beijing Municipal Science&Technology Commission(Beijing Brain Initiative),No.Z201100005520018(to JL)。
文摘Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°C.We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort.Plasma samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline project.These samples were stored at-80°C for up to 6 years before being used in this study.Our results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage time.However,the level of total tau showed a negative correlation with sample storage time.Notably,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage time.This was not observed in individuals with cognitive impairment.Consequently,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time.Therefore,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's disease.Furthermore,in cohort studies,it is important to consider the impact of storage time on the overall results.
文摘Newcastle disease (ND) virus is a leading threat to commercial and domestic poultry in Pakistan. The virus infects and constitutes irreversible impairment to the nervous system, damages the respiratory system, and marks severe gastrointestinal lesions leading to heavy mortality in short-living birds and substantial losses in layers and breeders. The continuous emergence and evolution of the virus made it inclined to evade the humoral response and indirectly the circumvention of artificial active immunization. Newcastle disease is caused by the orthoavula genus of the paramyxoviridae family and has shown high genetic diversity even in their genotypes while information regarding enzootic trends of the virus is scanty in Pakistan. A total of 40 tracheal samples of NDV were collected from different commercial broiler farms and 11 isolates of NDV were identified. In the current study, we determined the genetic diversity of the Newcastle disease virus based on the partial sequencing of the fusion protein gene available in the NCBI database. Genetic analysis showed that seven isolates belonged to class I genotype VII and four belonged to class II genotype II. Interestingly, two isolates had epidemiological connections with vaccine-like class II genotype II. Our findings, concerning the recent outbreaks of class I genotype VII and class II genotype II of NDV in vaccinated commercial flocks, suggest possible potential partial mutations in the fusion protein gene. Genetic diversity and formation of the new cleavage site in an important neutralizing protein of wild strain are linked with the potency of artificial active immunization and a major cause of vaccine failure.
文摘Branched chain amino acids(BCAAs)have been shown to affect gene expression,protein metabolism,apoptosis and regeneration of hepatocytes,and insulin resistance.They have also been shown to inhibit the proliferation of liver cancer cells in vitro,and are essential for lymphocyte proliferation and dendritic cell maturation.In patients with advanced chronic liver disease,BCAA concentrations are low,whereas the concentrations of aromatic amino acids such as phenylalanine and tyrosine are high,conditions that may be closely associated with hepatic encephalopathy and the prognosis of these patients.Based on these basic observations,patients with advanced chronic liver disease have been treated clinically with BCAA-rich medicines,with positive effects.
基金Supported by Italian Society for Celiac Disease and Foundation for Celicac Disease,No.007_FC_2016Regione Toscana(The Programma Attuativo Regionale Toscana funded by FAS),No.MICp ROBIMM
文摘BACKGROUND An altered (dysbiosis) and unhealthy status of the gut microbiota is usually responsible for a reduction of short chain fatty acids (SCFAs) concentration. SCFAs obtained from the carbohydrate fermentation processes are crucial in maintaining gut homeostasis and their determination in stool samples could provide a faster, reliable and cheaper method to highlight the presence of an intestinal dysbiosis and a biomarker for various gut diseases. We hypothesize that different intestinal diseases, such as celiac disease (CD), adenomatous polyposis (AP) and colorectal cancer (CRC) could display a particular fecal SCFAs’ signature. AIM To compare the fecal SCFAs’ profiles of CD, AP, CRC patients and healthy controls, using the same analytical method. METHODS In this cross-sectional study, we defined and compared the SCFAs’ concentration in fecal samples of 9 AP, 16 CD, 19 CRC patients and 16 healthy controls (HC). The SCFAs’ analysis were performed using a gas-chromatography coupled with mass spectrometry method. Data analysis was carried out using Wilcoxon ranksum test to assess pairwise differences of SCFAs’ profiles, partial least squaresdiscriminate analysis (PLS-DA) to determine the status membership based on distinct SCFAs’ profiles, and Dirichlet regression to determine factors influencing concentration levels of SCFAs. RESULTS We have not observed any difference in the SCFAs’ amount and composition between CD and healthy control. On the contrary, the total amount of SCFAs was significantly lower in CRC patients compared to HC (P = 0.044) and CD (P = 0.005). Moreover, the SCFAs’ percentage composition was different in CRC and AP compared to HC. In detail, HC displayed higher percentage of acetic acid (P value = 1.3 × 10-6) and a lower amount of butyric (P value = 0.02192), isobutyric (P value = 7.4 × 10-5), isovaleric (P value = 0.00012) and valeric (P value = 0.00014) acids compared to CRC patients. AP showed a lower abundance of acetic acid (P value = 0.00062) and higher percentages of propionic (P value = 0.00433) and isovaleric (P value = 0.00433) acids compared to HC. Moreover, AP showed higher levels of propionic acid (P value = 0.03251) and a lower level of isobutyric acid (P value = 0.00427) in comparison to CRC. The PLS-DA model demonstrated a significant separation of CRC and AP groups from HC, although some degree of overlap was observed between CRC and AP. CONCLUSION Analysis of fecal SCFAs shows the potential to provide a non-invasive means of diagnosis to detect patients with CRC and AP, while CD patients cannot be discriminated from healthy subjects.
基金supported in part by"National S&T Major Project Foundation of China"(2009ZX10004-904)Universities Natural Science Foundation of Jiangsu Province(09KJB330004),National Science Foundation Grant DMS-9971405National Institutes of Health Contract N01-HV-28183
文摘This paper first applies the sequential cluster method to set up the classification standard of infectious disease incidence state based on the fact that there are many uncertainty characteristics in the incidence course.Then the paper presents a weighted Markov chain,a method which is used to predict the future incidence state.This method assumes the standardized self-coefficients as weights based on the special characteristics of infectious disease incidence being a dependent stochastic variable.It also analyzes the characteristics of infectious diseases incidence via the Markov chain Monte Carlo method to make the long-term benefit of decision optimal.Our method is successfully validated using existing incidents data of infectious diseases in Jiangsu Province.In summation,this paper proposes ways to improve the accuracy of the weighted Markov chain,specifically in the field of infection epidemiology.
文摘Objective To establish a multiplex polymerase chain reaction (M-PCR) assay for simultaneous detection of pathogens causing genital ulcer disease (GUD). Mothods Based on the gene-specific region of the following pathogens: Chlamydia trachomatis omp l/ompb, herpes simplex virus (HSV) DNA polymerase, Treponema pollidum tpp47, Haemophilus ducreyi 16s rRNA, four sets of primers were designed and an M-PCR assay was developed to detect four pathogens in one test. The assay was evaluated with diagnostic result of golden standard for each pathogen.Results Of the 51 clinical samples, M-PCR showed slightly higher positive rate (47.1%) of HSV than cell culture (23.6%). Meanwhile, the positive rate of T. pallidum detected by M-PCR and dark-field microscopy was 19.6% (10/51) and 15.7% (8/51), respectively. Only one sample was positive for H. ducreyi and no sample was positive for C. trachomatis detected by both M-PCR assay and culture. Conclusion This primary study indicated that M-PCR assay can simultaneously and rapidly detect the four etiologic pathogens causing GUD.
文摘The present paper reports 11 cases of light chain disease (LCD) sequently found in several citles over Fujian province, Immunological classification of this group of LCD ww as follows: six of me cases belonged to type λ, four of them were type κ, and another one was a double LCD. We found that LCD was common in Fujlan only next to multiple myeloma (MM) of IgG class and accounted for 20% of the total 55 MM cases found in recent yean.It to well known that In matt patients of LCD M protein or Bence Jones proteinemia (BJPemia) to not detectable by conventional electro-phoresis. Our studies show that by making serum protein along with urinary BJP electrophoresis on the same one gel plate the sltuation can be greatly Improved It not only favour* the recognition of smail and faint band or bands of free light chain in serum, but also provides a repid and sensitive way, i. e. , immunofixation, to directly detect urinary light chain on the gel plate Immediately after electrophresis has been run.
基金the National Natural Science Foundation of China,No. 30670741
文摘Intracranial delivery of human Fc-deleted antibody specific to amyloid-β peptide (Aβ, anti-Aβ single-chain Fv, scFv) via adeno-associated virus (AAV) inhibits amyloid deposition in transgenic mice. However, the effects of AAV-mediated Fc-deleted antibody on animal behavior remain unclear. In this study, the anti-Aβ scFv antibody gone, isolated from phage display, was fused to the 5' end of the scFv antibody gone for antibody secretion by 2 rounds of polymerase chain reaction amplification. The fused antibody cDNA was cloned into a pSNAV2 plasmid under the control of the cytomegalovirus promoter. The sequence verified expression vector pSNAV2/scFv was transferred to BHK-21 ceils, and stable transfected BHK-21/scFv cells were established by G418 selection and infected with the recombinant herpes simplex virus rHSV/repcap for AAV production. Recombinant AAV was injected into the left quadriceps femoris of PDAPP transgenic mice. After 3 months, Morris water-maze results confirmed significantly improved cognitive function in a mouse model of Alzheimer's disease. Key Words: Alzheimer's disease; adeno-associated virus; amyloid-β peptide; single-chain antibody; neurodegenerative diseases; neural regeneration
文摘Very long chain fatty acids (VLCFAs) are accumulated in cells and blood in patients with peroxisomal diseases, such as adrenoleukodystrophy (ALD) and Zellwger Syndrome (ZS). The purpose of this study is to investigate usefulness of Fourier transform infrared spectroscopy (FTIR) with attenuated total reflection (ATR) analysis method for clinical diagnosis of those diseases, thereby we measured the infrared spectra of the sera of patients and healthy controls. Correlation coefficients between 2nd derivative FTIR spectra of the serum samples and the VLCFA content ratio which is used as a clinical parameter to date were comprehensively calculated to investigate which wavenumber showed high correlation with the VLCFA ratio. Multiple regression analysis using the serum FTIR spectra showed that high correlations were observed with VLCFA ratios (C26:0/C22:0 ratio), and we could construct a suitable regression model (R2 = 0.97, p ﹣19). In addition, the model system using various VLCFAs in newborn bovine serum also showed that several FTIR peaks in 800 ~ 900 cm﹣1 region were found to have good correlation with VLCFA ratios. Our results support that FTIR analysis is useful for diagnosis of peroxisomal diseases.
文摘IgG Heavy Chain Disease (γHCD) is a rare plasma cell disorder. Hypercalcemia related to plasma cell dyscrasias is related to non-PTHrP related mechanisms. Here we describe the first case of a patient with γHCD and PTHrP related hypercalcemia. Methods: Patient case derived from chart review from 2011 to 2015. Literature review performed searching PubMed 1968-current. Results: The patient was diagnosed with hypercalcemia with elevated PTHrP and exclusion of other etiologies of hypercalcemia. She was diagnosed with (γHCD) by M-spike 0.64 g/dL, IFE showing a broad band of IgG heavy chain, without associated light chains and severe depression of the non-mono-clonal IgG. Serum immunoglobulins demonstrated elevated IgG (2110 mg/dL), normal IgA (46 mg/dL) and decreased IgM (<21 mg/dL). Bone marrow biopsy showed 5% PCs, non-clonal by kappa/lambda, but exclusive for IgG by IHC, without any staining for IgA or IgM. The patient was started on therapy with improved hypercalcemia and PTHrP levels. Conclusions: This is the first reported case of γHCD presenting with PTHrP related hypercalcemia. Given that skeletal involvement is uncommon in γHCD, hypercalcemia secondary to γHCD may at times be a PTHrP driven phenomenon and we recommend that this test be ordered in such cases.
基金supported by the National Natural Science Foundation of China,No.81274005Medical Science Research,Health Department of Hebei Province,No.20110173,20090588Hebei Education Department Science Foundation,No.2007302
文摘Oxidative stress and mitochondrial damage have been implicated in the pathogenesis of several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Oxidative stress is characterized by the overproduction of reactive oxygen species, which can induce mitochondrial DNA mutations, damage the mitochondrial respiratory chain, alter membrane permeability, and influence Ca2+ homeostasis and mitochondrial defense systems. All these changes are implicated in the development of these neurodegenerative diseases, mediating or amplifying neuronal dysfunction and triggering neurodegeneration. This paper summarizes the contribution of oxidative stress and mitochondrial damage to the onset of neurodegenerative diseases and discusses strategies to modify mitochondrial dysfunction that may be attractive therapeutic interventions for the treatment of various neurodegenerative diseases.
基金Supported by Inha University Research Grant and Korean Food and Drug Administration
文摘AIM: To compare the histopathologic features of intestinal tuberculosis (ITB) and Crohn’s disease (CD) and to identify whether polymerase chain reaction for Mycobacterium tuberculosis (TB-PCR) would be helpful for differential diagnosis between ITB and CD.METHODS: We selected 97 patients with established diagnoses (55 cases of ITB and 42 cases of CD) who underwent colonoscopic biopsies.Microscopic features of ITB and CD were reviewed,and eight pathologic parameters were evaluated.Nine cases of acid fast bacilli culture-positive specimens and 10 normal colonic tissue specimens were evaluated as the positive and negative control of the TB-PCR test,respectively.PCR assays were done using two commercial kits: kit <A> detected IS6110 and MPB64,and kit <B> detected IS6110 only;a manual in-house PCR method was also performed on formalin-fi xed,paraffi n-embedded colonoscopic biopsy specimens.RESULTS: Statistically significant differences were noted between ITB and CD with regard histopathologic criteria: size of granulomas (P = 0.000),giant cells (P = 0.015),caseation necrosis (P = 0.003),confluent granulomas (P = 0.001),discrete granulomas (P = 0.000),and granulomas with lymphoid cuffs (P = 0.037).However,29 cases (52.7%) of ITB showed less than fi ve kinds of pathologic parameters,resulting in confusion with CD.The sensitivities and specificities of the TB-PCR test by kit <A>,kit <B>,and the in-house PCR method were 88.9% and 100%,88.9% and 100%,and 66.7% and 100% in positive and negative controls,respectively.The PCR test done on endoscopic biopsy specimens of ITB and CD were signifi cantly different with kit <A> (P = 0.000) and kit <B> (P = 0.000).The sensitivities and specifi cities of TB-PCR were 45.5% and 88.1%,36.4% and 100%,and 5.8% and 100%,for kit <A> and kit <B> and inhouse PCR method on endoscopic biopsy specimens.Among the 29 cases of histopathologically confusing CD,10 cases assayed using kit <A> and 6 cases assayed using kit <B> were TB-PCR positive.A combination of histologic fi ndings and TB-PCR testing led to an increase of diagnostic sensitivity and the increase (from 47.3% to 58.2) was statistically signifi cant with kit <B> (P = 0.000).CONCLUSION: The TB-PCR test combined with histopathologic factors appears to be a helpful technique in formulating the differential diagnosis of ITB and CD in endoscopic biopsy samples.
文摘Cytomegalovirus(CMV) infection is common in humans.The virus then enters a "latency phase" and can reactivate to different stimuli such as immunosuppression.The clinical significance of CMV infection in inflammatory bowel disease is different in Crohn's disease(CD) and ulcerative colitis(UC).CMV does not interfere in the clinical course of CD.However,CMV reactivation is frequent in severe or steroid-resistant UC.It is not known whether the virus exacerbates the disease or simply appears as a bystander of a severe disease.Different methods are used to diagnose CMV colitis.Diagnosis is classically based on histopathological identification of viral-infected cells or CMV antigens in biopsied tissues using haematoxylin-eosin or immunohistochemistry,other tests on blood or tissue samples are currently being investigated.Polymerase chain reaction performed in colonic mucosa has a high sensitivity and a positive result could be associated with a worse prognosis disease;further studies are needed to determine the most appropriate strategy with positive CMV-DNA in colonic mucosa.Specific endoscopic features have not been described in active UC and CMV infection.CMV colitis is usually treated with ganciclovir for several weeks,there are different opinions about whether or not to stop immunosuppressive therapy.Other antiviral drugs may be used.Multicenter controlled studies would needed to determine which subgroup of UC patients would benefit from early antiviral treatment.
基金Science Fund of Military Medical Science for the Ninth Five-Year Key Research,No.98Z073
文摘INTRODUCTIONAlthough several specific detecting methods hadbeen applied to determine the hepatitis virus,therewas a lot of cryptogenic hepatitis without anyknown hepatitis infectious marker.Theprevalence of hepatitis G virus (HGV) (also knownas GB-C virus) infection has been reported to be 5%-13% in patients with non-A-E hepatitis andcirrhosis,however,there is little evidencesuggesting that HGV causes hepatitis in human.
基金Supported by A grant from Fundación de Investigación Médica Mutua Madrilena(FMM)(to Díaz-Rubio M)
文摘AIM:To examine the detection rate of viable Mycobacterium avium subspecies paratuberculosis(MAP) in patients with inflammatory bowel disease [Crohn's disease(CD) and ulcerative colitis(UC)].METHODS:Thirty patients with CD(15 with at least one NOD2/CARD15 mutation),29 with UC,and 10 with no inflammatory bowel disease(IBD).were tested for MAP by polymerase chain reaction(specific IS900 fragment) and blood culture.RESULTS:MAP DNA was detected in all original blood samples and 8-wk blood cultures(CD,UC and non-IBD).Positive MAP DNA status was confirmed by dot blot assays.All 69 cultures were negative by acid-fast Ziehl-Neelsen staining.Viable MAP,in spheroplast form,was isolated from the 18-mo blood cultures of all 30 CD patients,one UC patient,and none of the non-IBD controls.No association was found between positive MAP cultures and use of immunosuppressive drugs or CDassociated single nucleotide polymorphisms.CONCLUSION:MAP is widely present in our area and MAP DNA can be recovered from the blood of CD,UC and non-IBD patients.However,MAP spheroplasts were only found in CD patients.
文摘Mitochondria are one of the major sites for the genera-tion of reactive oxygen species(ROS) as an undesirable side product of oxidative energy metabolism. Damaged mitochondria can augment the generation of ROS. Dys-function of mitochondria increase the risk for a large number of human diseases, including cardiovascular diseases(CVDs). Heart failure(HF) following ischemic heart disease, infantile cardiomyopathy and cardiac hypertrophy associated with left ventricular dilations are some of the CVDs in which the role of mitochon-drial oxidative stress has been reported. Advances in mitochondrial research during the last decade focused on the preservation of its function in the myocardium, which is vital for the cellular energy production. Expe-rimental and clinical trials have been conducted using mitochondria-targeted molecules like: MnSOD mimetics, such as EUK-8, EUK-134 and MitoSOD; choline esters of glutathione and N-acetyl-L-cysteine; triphenylphospho-nium ligated vitamin E, lipoic acid, plastoquinone andmitoCoQ10; and Szeto-Schiller(SS)- peptides(SS-02 and SS-31). Although many results are inconclusive, some of the findings, especially on CoQ10, are worthwhile. This review summarizes the role of mitochondria-tar-geted delivery of agents and their consequences in the control of HF.
基金supported by the National Natural Science Foundation of China,No.81403456,81473788a grant from the Hubei Provincial Collaborative Innovation Center of Preventive Treatment by Acupuncture and Moxibustion,No.HBPCIC-2016-003
文摘Defects in autophagy-mediated clearance of α-synuclein may be one of the key factors leading to progressive loss of dopaminergic neurons in the substantia nigra. Moxibustion therapy for Parkinson’s disease has been shown to have a positive effect, but the underlying mechanism remains unknown. Based on this, we explored whether moxibustion could protect dopaminergic neurons by promoting autophagy mediated by mammalian target of rapamycin (mTOR), with subsequent elimination of α-syn. A Parkinson’s disease model was induced in rats by subcutaneous injection of rotenone at the back of their necks, and they received moxibustion at Zusanli (ST36), Guanyuan (CV4)and Fengfu (GV16), for 10 minutes at every point, once per day, for 14 consecutive days. Model rats without any treatment were used as a sham control. Compared with the Parkinson’s disease group, the moxibustion group showed significantly greater tyrosine hydroxylase immunoreactivity and expression of light chain 3-II protein in the substantia nigra, and their behavioral score, α-synuclein immunoreactivity,the expression of phosphorylated mTOR and phosphorylated ribosomal protein S6 kinase (p-p70S6K) in the substantia nigra were significantly lower. These results suggest that moxibustion can promote the autophagic clearance of α-syn and improve behavioral performance in Parkinson’s disease model rats. The protective mechanism may be associated with suppression of the mTOR/p70S6K pathway.
基金Supported by Grant from the National Center for Global Health and Medicine
文摘Here,we report a case of fulminant gastrointestinal graft-versus-host disease(GI-GVHD) with cytomegalovirus(CMV) infection in 44-year-old woman.Despite the difficulties associated with the treatment of GIGVHD and GI-CMV disease,the mucosal findings and the clinical course showed marked improvements during long-term clinical observation.The endoscopic findings were remarkable,with diffuse sloughing mucosa in the stomach and highly active inflammation and deep discrete ulcers throughout the colon.Changes in the CMV quantitative polymerase chain reaction results were correlated with the endoscopic mucosal findings and were useful for assessing the efficacy of the treatment.Although a definite diagnosis of GI-GVHD is generally made by endoscopy with biopsy,the gross appearance of this disease can vary depending on the endoscopy.In this paper,we also conduct a literature review of patients with GI-GVHD.
文摘AIM:To define the parameters that positively predict diagnosis of Crohn's disease (CD) and differentiate it from gastrointestinal tuberculosis (GITB). METHODS:This prospective study over 3 years was carried out in the consecutive Indian patients with definite diagnosis of CD and equal numbers of patients with definite diagnosis of GITB. Demographic, clinical, laboratory, morphological and histological features were noted in all the patients. Serological tests such as p-ANCA, c-ANCA, IgA ASCA and IgG ASCA, were performed. Endoscopic biopsy and/or surgical tissue specimens were subjected to smear and culture for acid-fast bacilli (AFB) and tissue polymerase chain reaction for tuberculosis (TB PCR). Diagnosis of CD and GITB was based on the standard criteria. Data were analyzed using univariate Chi-square test and multiple logistic regression (MLR). RESULTS:The study is comprised of 26 patients with CD (age 36.6 ± 8.6 year, male:female, 16:10) and 26 patients with GITB (age 37.2 ± 9.6 year, male:female, 15:11). The following clinical variables between the two groups (CD vs TB) were significant in univariate analysis:duration of symptoms (58.1 ± 9.8 vs 7.2 ± 3.4 mo), diarrhoea (69.2% vs 34.6%), bleeding per rectum (30.7% vs 3.8%), fever (23.1% vs 69.2%), ascites (7.7% vs 34.6%) and extra-intestinal manifestations of inflammatory bowel disease (61.5% vs 23.1%). Of these, all except ascites and extra-colonic manifestations were found statistically significant by MLR. Accuracy of predicting CD was 84.62% based on the fever, bleeding P/R, diarrhoea and duration of symptoms while it was 63.4% when histology was reported as inflammatory bowel disease and 42.3% when there was recurrence of disease after surgery. Accuracy of predicting GITB was 73.1% when there was co-existing pulmonary lesions and/or abdominal lymphadenopathy;75% when tuberculosis was reported in histology;63.4% when granuloma was found in histology;82.6% when TB PCR was positive;and 61.5% when smear and/ or culture was positive for AFB. Serological test was not useful in differentiation of CD from GITB. Positivity rates for CD and GITB were:p-ANCA-3.8% and 3.8%, c-ANCA-3.8% and 0%, IgA ASCA-38.4% and 23.1%, and IgG ASCA-38.4% and 42.3%, respectively. CONCLUSION:Simple clinical parameters like fever, bleeding P/R, diarrhoea and duration of symptoms have the highest accuracy in differentiating CD from GITB.