The original online version of this article (Kamenarova, K., Cherninkova, S., Mihova, K., Georgiev, R., Nikolaeva, Y. and Kaneva, R. (2022) Identification of Novel Nonsense RPGR Variant Causing Mild X-Linked Cone-Rod ...The original online version of this article (Kamenarova, K., Cherninkova, S., Mihova, K., Georgiev, R., Nikolaeva, Y. and Kaneva, R. (2022) Identification of Novel Nonsense RPGR Variant Causing Mild X-Linked Cone-Rod Dystrophy and Myopia. Case Reports in Clinical Medicine, 11, 422-434. DOI: 10.4236/crcm.2022.1110059) unfortunately contains a mistake. The authors need to replace Figure 1.展开更多
AIM: To assess the effect of our novel cell-permeable nuclear factor-kappaB (NF-κB) inhibitor peptide PN50 in an experimental model of acute pancreatitis. PN50 was produced by conjugating the cell-penetrating penetra...AIM: To assess the effect of our novel cell-permeable nuclear factor-kappaB (NF-κB) inhibitor peptide PN50 in an experimental model of acute pancreatitis. PN50 was produced by conjugating the cell-penetrating penetratin peptide with the nuclear localization signal of the NF-κB p50 subunit.METHODS: Pancreatitis was induced in male Wistar rats by administering 2×100 μg/kg body weight of cholecystokininoctapeptide (CCK) intraperitoneally (IP) at an interval of 1 h. PN50-treated animals received 1 mg/kg of PN50 IP 30 min before or after the CCK injections. The animals were sacrificed 4 h after the first injection of CCK.RESULTS: All the examined laboratory (the pancreatic weight/body weight ratio, serum amylase activity,pancreatic levels of TNF-α and IL-6, degree of lipid peroxidation, reduced glutathione levels, NF-κB binding activity, pancreatic and lung myeloperoxidase activity) and morphological parameters of the disease were improved before and after treatment with the PN50 peptide.According to the histological findings, PN50 protected the animals against acute pancreatitis by favoring the induction of apoptotic, as opposed to necrotic acinar cell death associated with severe acute pancreatitis.CONCLUSION: Our study implies that reversible inhibitors of stress-responsive transcription factors like NF-κB might be clinically useful for the suppression of the severity of acute pancreatitis.展开更多
BACKGROUND: There is a growing evidence that matrix metalloproteinase (MMP)-2 and MMP-9 (gelatinases) play an important role in the pathogenesis of numerous disorders especially with inflammatory etiology and extracel...BACKGROUND: There is a growing evidence that matrix metalloproteinase (MMP)-2 and MMP-9 (gelatinases) play an important role in the pathogenesis of numerous disorders especially with inflammatory etiology and extracellular matrix (ECM) remodeling. Despite the fact that gelatinases involve in liver cirrhosis is provided in the literature, their role in the pathogenesis of chronic pancreatitis and non-specific inflammatory bowel diseases is still under investigation.DATA SOURCES: We carried out a PubM ed search of English language articles relevant to the involvement of gelatinases in the pathogenesis of liver fibrosis, pancreatitis, and non-specific inflammatory bowel diseases.RESULTS: The decreased activity of gelatinases, especially MMP-2, is related to the development of liver fibrosis, probably due to the decrease of capability for ECM remodeling. Similar situation can be found in chronic pancreatitis; however reports on this matter are rare. The presence of non-specific inflammatory bowel diseases results in MMP-9 activity elevation.CONCLUSION: The fluctuation of gelatinases activity during liver fibrosis, chronic pancreatitis and non-specific inflammatorybowel diseases is observed, but the exact role of these enzymes demands further studies.展开更多
Objective:To justify the use of African mistletoe(AM) Viscum album {V.album) in folkoric medicine to treat diabetes.Methods:In one experiment,the fasting blood glucose(FBG) leveb of diabetic rats were monitored for 4 ...Objective:To justify the use of African mistletoe(AM) Viscum album {V.album) in folkoric medicine to treat diabetes.Methods:In one experiment,the fasting blood glucose(FBG) leveb of diabetic rats were monitored for 4 h.Diabetic rats were treated with AM at doses of 50 mg/kg(AM1) and 100 mg/kg(AM2),glibenclamide(GB)(positive control) and saline solution(SS).In another experiment,diabetic rats were treated with AM2,GB and SS daily for 3 weeks.Results:AM1 and AM2 elicited significant(P【0.05) hypoglycaemic effects within 4 h of extract administration. AM1 and AM2 decreased the FBG by 41%and 49%,respectively,at 2 h.AM2 was found to lower FBC by 51%,relative to baseline,which was comparable to GB at 3 h.In the second experiment, AM2 and GB significantly(P【0.05) decreased the FBG by 34%and 51%,respectively.This was followed by marked decrease in levels of HbAlC in AM2- and GB- treated diabetic rats.AM2 significantly(P【0.05) decreased the STZ-induced increase in levels of serum triglyceride,urea, lactate dehydrogenase,α-amylase and low-density lipoprotein-cholesterol.Furthermore, diabetic rats treated with AM2 had significanlly(P【0.05) elevated high-density lipoprotein-cholesterol. In contrast,STZ administration produced insignificant(P【0.05) effect on the levels of serum creatinine and total bilirubin.Conclusions:Extract of African mistletoe has anti-diabetic and anti-hyperlipidemic effects in STZ-diabetic rats.AM may find clinical application in the amelioration of diabetes-induced lipid disorders.展开更多
Gastrointestinal diseases, specifically Crohn's disease, ulcerative colitis, diverticular disease, and primary biliary cirrhosis are all characterized by complicated inflammation of the digestive tract. Their path...Gastrointestinal diseases, specifically Crohn's disease, ulcerative colitis, diverticular disease, and primary biliary cirrhosis are all characterized by complicated inflammation of the digestive tract. Their pathology is multifactorial, and risk factors encompass both genetic and environmental factors. Recent advances in the genetic component of inflammatory bowel diseases(IBDs) have revealed that the tumor necrosis factor superfamily member 15(TNFSF15) contains a number of risk alleles associated not only with IBD but also with other diseases such as diverticular disease and primary biliary cirrhosis. These risk alleles in TNFSF15 and the altered expression of its gene product can serve as the common ground between these disorders by explaining at least some of the underlying processes that lead to a dysregulated immune response and subsequent chronic inflammation. Here, we aim to outline how the TNFSF15 gene is involved in the proliferation and cell fate of different populations of T cells and subsequently in the control of both pro-and anti-inflammatory cytokines. Furthermore, we summarize what is currently known of TNFSF15 control region variants, how they are associated with each mentioned disease, and how these variants can explain the autoimmune pathology of said diseases through altered TNFSF15 expression.展开更多
In this paper, we report the design and moleculardocking study of analogues of antimycin A3 as inhibitors of anti-apoptotic Bcl-2 of breast cancer. Twenty designed compounds and the original antimycin A3 were docked b...In this paper, we report the design and moleculardocking study of analogues of antimycin A3 as inhibitors of anti-apoptotic Bcl-2 of breast cancer. Twenty designed compounds and the original antimycin A3 were docked based on their interaction with breast tumor receptor binding target Bcl-2. The docking resulted in the five top-ranked compounds, namely, compounds 11, 14, 15, 16, and 20, which have a lower G binding energy, better affinity and stronger hydrogen bonding interactions to the active site of Bcl-2 than antimycin A3. Among those five top-ranked compounds, analogue compounds 11 and 14, which have an 18-membered tetralactone core and 18-membered tetraol core, respectively, exhibited the strongest hydrogen bond interaction, formed high stability conformation, and demonstrated the greatest inhibitory activity on the catalytic site of Bcl-2.展开更多
UV-VIS spectroscopic investigations of interaction of bovine and human serum albumin with selected chalcones (1) and their cyclic chalcone analogues: (E)-2-(4’-X-benzylidene-1-tetralones (3), benzosuberones (4) with ...UV-VIS spectroscopic investigations of interaction of bovine and human serum albumin with selected chalcones (1) and their cyclic chalcone analogues: (E)-2-(4’-X-benzylidene-1-tetralones (3), benzosuberones (4) with dimethylamino and methoxy substituents and (E)-2-(2’,4’-dimethox- ybenzylidene)-1-indanone (2) were performed in polar respiration medium. Absorption maxima of the tested compounds were investigated in the presence of bovine and human serum albumin at the 0, 10, 30 and 60 minute timepoints of the interaction. The absorbance of all studied compounds in the presence of proteins decreased after one hour of the reaction. Molecule 4a showed the strongest and fastest kinet initial interaction with both albumins.展开更多
The title complex bis(2-acetylpyridine thiosemicarbazonato)-indium(iii) perchlo-rate hydrate has been synthesized by the reaction of 2-acetylpyridine thiosemicarbazide(L) with indium(iii) perchlorate,and its structure...The title complex bis(2-acetylpyridine thiosemicarbazonato)-indium(iii) perchlo-rate hydrate has been synthesized by the reaction of 2-acetylpyridine thiosemicarbazide(L) with indium(iii) perchlorate,and its structure was characterized by elemental analysis,IR and single-crystal X-ray diffraction.The crystal of the title compound([In(C8H9N4S)2]ClO4·H2O) belongs to monoclinic,space group P21/c with a = 12.6438(18),b = 12.6259(18),c = 15.116(2) nm,β = 105.800(2)°,Z = 4,V = 2321.9(6) nm3,Mr = 618.79,Dc = 1.770 g/cm3,μ = 1.359 mm-1,F(000) = 1240,R = 0.0265 and wR = 0.0675.X-ray analysis indicates that various intriguing hydrogen patterns involving both the solvent intermedia and polyatomic counterions play crucial roles in the self-assembly of functional supramolecules.展开更多
Each eukaryotic cell of multicellular organisms must be able to maintain its integrity by sensing both external and internal stimuli. The primary goal of the generated response mechanism is to drive back the system to...Each eukaryotic cell of multicellular organisms must be able to maintain its integrity by sensing both external and internal stimuli. The primary goal of the generated response mechanism is to drive back the system to the former or to a new homeostatic state. Moreover, the response has to provide an accurate survival-or-death decision to avoid any “misunderstanding” and its unwanted consequences. New data revealed that a systems-level crosstalk of molecular networks has an essential role in achieving the correct characteristic of the response. Although many molecular components of these processes already have been revealed, several elements and regulatory connections of crosstalk are still missing. These “gaps” of the complex control networks make hardly impossible to present comprehensive models. Therefore we approach the questions from a systems biology aspect by combining the experimental results with the special technique of mathematical modelling. In this short report we discuss some novel and preliminary data gained by this approach on the crosstalk between life and death decisions under cellular stress, to get a systems biological view of these networks.展开更多
BACKGROUND The B.1.617.2(delta)variant of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was first discovered in Maharashtra in late 2020 and has rapidly expanded across India and worldwide.It took only 2 ...BACKGROUND The B.1.617.2(delta)variant of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was first discovered in Maharashtra in late 2020 and has rapidly expanded across India and worldwide.It took only 2 mo for this variant to spread in Indonesia,making the country the new epicenter of the delta variant as of July 2021.Despite efforts made by accelerating massive rollouts of current vaccines to protect against infection,cases of fully-vaccinated people infected with the delta variant have been reported.AIM To describe the demographic statistics and clinical presentation of the delta variant infection after the second dose of vaccine in Indonesia.METHODS A retrospective,single-centre case series of the general consecutive population that worked or studied at Faculty of Medicine,Universitas Indonesia with confirmed Delta Variant Infection after a second dose of vaccine from 24 June and 25 June 2021.Cases were collected retrospectively based on a combination of author recall,reverse transcription-polymerase chain reaction(RT-PCR),and whole genome sequencing results from the Clinical Microbiology Laboratory,Faculty of Medicine,Universitas Indonesia.RESULTS Between 24 June and 25 June 2021,15 subjects were confirmed with the B.1.617.2(delta)variant infection after a second dose of the vaccine.Fourteen subjects were vaccinated with CoronaVac(Sinovac)and one subject with ChAdOx1 nCoV-19(Oxford-AstraZeneca).All of the subjects remained in home isolation,with fever being the most common symptom at the onset of illness(n=10,66.67%).The mean duration of symptoms was 7.73 d(±5.444).The mean time that elapsed from the first positive swab to a negative RT-PCR test for SARS-CoV-2 was 17.93 d(±6.3464).The median time that elapsed from the second dose of vaccine to the first positive swab was 87 d(interquartile range:86-128).CONCLUSION Although this case shows that after two doses of vaccine,subjects are still susceptible to the delta variant infection,currently available vaccines remain the most effective protection.They reduce clinical manifestations of COVID-19,decrease recovery time from the first positive swab to negative swab,and lower the probability of hospitalization and mortality rate compared to unvaccinated individuals.展开更多
Interaction of the synthetic chalcones (1b,1c) and their cyclic analogues (2b,2c) with bovine (BSA) and human serum albumin (HSA) as well as with rat liver mitochondria (RLM) was studied by fluorescence spectroscopy. ...Interaction of the synthetic chalcones (1b,1c) and their cyclic analogues (2b,2c) with bovine (BSA) and human serum albumin (HSA) as well as with rat liver mitochondria (RLM) was studied by fluorescence spectroscopy. The maxima of emission fluorescence spectra were changed only in the case of 2b and 2c during interaction with BSA, HSA as well as mitochondrial outer membrane showing a slight hypsochromic shift and decrease of fluorescence. Interaction of the methoxy-(1b,2b) and the dimethylamino-substituted (1c,2c) compounds with outer mitochondrial membrane were studied by fluorescence polarization. Fluorescence polarization of 1b in the presence of the two proteins and mitochondria was found to be unchanged. Under similar conditions (2b,1c,2c) showed continuously increasing fluorescence polarization signal during the 30 minute period of investigations. Since fluorescence polarization supposes that as a result of binding these substances to proteins and lipids. Compound 2c displayed a continuous increase of fluorescence polarization signal in the presence of proteins (BSA, HSA), yeast cytoplasm (YC) and mitochondria (YM and RLM). This compound displayed a significant cytotoxic effect. This pattern of interaction with proteins might be one of the contributing vectors of the observed cytotoxicity against several human carcinoma cell lines.展开更多
Background: Mutations in the RPGR gene are associated with rod-cone or cone-rod dystrophy, the latter associated with mutations at the distal end. Cone-rod dystrophy (CRD) is a subgroup of hereditary retinal disorders...Background: Mutations in the RPGR gene are associated with rod-cone or cone-rod dystrophy, the latter associated with mutations at the distal end. Cone-rod dystrophy (CRD) is a subgroup of hereditary retinal disorders characterized by the primary degeneration of cone photoreceptors often followed by progressive loss of rod photoreceptors in the peripheral visual field. Purpose: The aim of this study was to describe the milder CRD phenotype associated with a novel pathogenic variant c.1905 + 223C > T (p.Q710X) found in RPGR which results in shortening of the photoreceptor specific isoform RPGR <sup>ORF15</sup>. Method: An 11-year-old boy with symptoms of CRD and two female relatives were referred for detailed ophthalmic examinations. Genetic testing was performed by next-generation sequencing of clinical exome followed by Sanger sequencing for segregation analysis. Results: Genetic analysis identified a novel variant in ORF15 of the RPGR gene (c.1905 + 223C > T, p.Q710X) in the proband considered as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) standards. Segregation study identified the mutation in a heterozygous state in the mother and her sister. Detailed ophthalmological examination revealed slightly reduced color vision and scattered grayish point-like deposits in the posterior pole of the fundus in the male patient. All mutation carriers were myopic. Conclusion: We report a novel pathogenic RPGR variant in a Bulgarian patient with clinical features compatible with the CRD diagnosis. This condition is inherited as an X-linked dominant trait in its familial form presenting with a mild CRD phenotype in the male hemizygous proband and a moderate to high myopia in the female heterozygous carriers.展开更多
The integration of the civics course and surveying professional course is an important part of the teaching reform of surveying,which is an important way to implement the principle of cultivating educated talents with...The integration of the civics course and surveying professional course is an important part of the teaching reform of surveying,which is an important way to implement the principle of cultivating educated talents with moral characters for the country.Based on the surveying course,this paper deeply analyses the spirit of hard work and endurance,craftsmanship,innovation,and national sentiment contained in surveying,carries the civics education with professional knowledge,and makes the civics element subliminally enter the brain and heart,so as to improve the patriotic sentiment and professional quality of students.展开更多
Colorectal cancer(CRC) is fourth most common cancer in men and third in women worldwide. Developing a diagnostic panel of sensitive and specific biomarkers for the early detection of CRC is recognised as to be crucial...Colorectal cancer(CRC) is fourth most common cancer in men and third in women worldwide. Developing a diagnostic panel of sensitive and specific biomarkers for the early detection of CRC is recognised as to be crucial for early initial diagnosis, which in turn leads to better long term survival. Most of the research on novel potential CRC biomarkers in the last 2 decades has been focussed on stool DNA analysis. In this paper, we describe the recent advances in non-invasive CRC screening and more specifically in molecular assays for aberrantly methylated BMP3 and NDRG4 promoter regions. In several research papers these markers showed superior rates for sensitivity and specificity in comparison to previously described assays. These tests detected the majority of adenomas ≥ 1 cm in size and the detection rates progressively increased with larger adenomas. The methylation status of the BMP3 and NDRG4 promoters demonstrated effective detection of neoplasms at all sites throughout the colon and was not affected by common clinical variables. Recently, a multitarget stool DNA test consisting of molecular assays for aberrantly methylated BMP3 and NDRG4 promoter regions, mutant KRAS and immunochemical assay for human haemoglobin has been made commercially available and is currently reimbursed in the United States. Although this is the most sensitive noninvasive CRC screening test, there is the need for further research in several areas- establishment of the best timeframe for repeated DNA stool testing; validation of the results in populations outside of North America; usefulness for surveillance and prognosis of patients; cost-effectiveness of DNA stool testing in real-life populations.展开更多
Obesity due to excessive food intake and the lack of physical activity is becoming one of the most serious public health problems of the 21stcentury. With the increasing prevalence of obesity, non-alcoholic fatty live...Obesity due to excessive food intake and the lack of physical activity is becoming one of the most serious public health problems of the 21stcentury. With the increasing prevalence of obesity, non-alcoholic fatty liver disease is also emerging as a pandemic. While previously this pathophysiological condition was mainly attributed to triglyceride accumulation in hepatocytes,recent data show that the development of oxidative stress, lipid peroxidation, cell death, inflammation and fibrosis are mostly due to accumulation of fatty acids,and the altered composition of membrane phospholipids. In fact, triglyceride accumulation might play a protective role, and the higher toxicity of saturated or trans fatty acids seems to be the consequence of a blockade in triglyceride synthesis. Increased membrane saturation can profoundly disturb cellular homeostasis by impairing the function of membrane receptors,channels and transporters. However, it also inducesendoplasmic reticulum stress via novel sensing mechanisms of the organelle's stress receptors. The triggered signaling pathways in turn largely contribute to the development of insulin resistance and apoptosis. These findings have substantiated the lipotoxic liver injury hypothesis for the pathomechanism of hepatosteatosis.This minireview focuses on the metabolic and redox aspects of lipotoxicity and lipoapoptosis, with special regards on the involvement of endoplasmic reticulum stress responses.展开更多
AIM: To establish the therapeutic potential of proteasome inhibition, we examined the therapeutic effects of MG132 (Z-Leu-Leu-Leu-aldehyde) in an experimental model of acute pancreatitis.METHODS: Pancreatitis was indu...AIM: To establish the therapeutic potential of proteasome inhibition, we examined the therapeutic effects of MG132 (Z-Leu-Leu-Leu-aldehyde) in an experimental model of acute pancreatitis.METHODS: Pancreatitis was induced in rats by two hourly intraperitoneal (ip) injections of cholecystokinin octapeptide (CCK; 2 x 100 μg/kg) and the proteasome inhibitor MG132 (10 mg/kg ip) was administered 30 min after the second CCK injection. Animals were sacrificed 4 h after the first injection of CCK.RESULTS: Administering the proteasome inhibitor MG132 (at a dose of 10 mg/kg, ip) 90 min after the onset of pancreatic inflammation induced the expression of cell-protective 72 kDa heat shock protein (HSP72) and decreased DNA-binding of nuclear factor-kB (NF-kB). Furthermore MG132 treatment resulted in milder inflammatory response and cellular damage, as revealed by improved laboratory and histological parameters of pancreatitis and associated oxidative stress.CONCLUSION: Our findings suggest that proteasome inhibition might be beneficial not only for the prevention, but also for the therapy of acute pancreatitis.展开更多
The metabolic syndrome, one of the most common clinical conditions in recent times, represents a combination of cardiometabolic risk determinants, including central obesity, glucose intolerance, insulin resistance, dy...The metabolic syndrome, one of the most common clinical conditions in recent times, represents a combination of cardiometabolic risk determinants, including central obesity, glucose intolerance, insulin resistance, dyslipidemia, non-alcoholic fatty liver disease and hypertension. Prevalence of the metabolic syndrome is rapidly increasing worldwide as a consequence of common overnutrition and consequent obesity. Although a unifying picture of the pathomechanism is still missing, the key role of the pre-receptor glucocorticoid activation has emerged recently. Local glucocorticoid activation is catalyzed by a triad composed of glucose-6-phosphate-transporter, hexose-6-phosphate dehydrogenase and 11β-hydroxysteroid dehydrogenase type 1 in the endoplasmic reticulum. The elements of this system can be found in various cell types, including adipocytes and hepatocytes. While the contribution of glucocorticoid activation in adipose tissue to the pathomechanism of the metabolic syndrome has been well established, the relative importance of the hepatic process is less understood. This review summarizes the available data on the role of the hepatic triad and its role in the metabolic syndrome, by confronting experimental findings with clinical observations.展开更多
Diabetic neuropathy is one of the most serious complications of diabetes, and its increase shows no sign of stopping. Furthermore, current clinical treatments do not yet approach the best effectiveness. Thus, the deve...Diabetic neuropathy is one of the most serious complications of diabetes, and its increase shows no sign of stopping. Furthermore, current clinical treatments do not yet approach the best effectiveness. Thus, the development of better strategies for treating diabetic neuropathy is an urgent matter. In this review, we first discuss the advantages and disadvantages of some major mouse models of diabetic neuropathy and then address the targets for mechanism-based treatment that have been studied. We also introduce our studies on each part. Using stem cells as a source of neurotrophic factors to target extrinsic factors of diabetic neuropathy, we found that they present a promising treatment.展开更多
文摘The original online version of this article (Kamenarova, K., Cherninkova, S., Mihova, K., Georgiev, R., Nikolaeva, Y. and Kaneva, R. (2022) Identification of Novel Nonsense RPGR Variant Causing Mild X-Linked Cone-Rod Dystrophy and Myopia. Case Reports in Clinical Medicine, 11, 422-434. DOI: 10.4236/crcm.2022.1110059) unfortunately contains a mistake. The authors need to replace Figure 1.
基金Supported by the National Research Foundation (OTKA) T30735 and T042589
文摘AIM: To assess the effect of our novel cell-permeable nuclear factor-kappaB (NF-κB) inhibitor peptide PN50 in an experimental model of acute pancreatitis. PN50 was produced by conjugating the cell-penetrating penetratin peptide with the nuclear localization signal of the NF-κB p50 subunit.METHODS: Pancreatitis was induced in male Wistar rats by administering 2×100 μg/kg body weight of cholecystokininoctapeptide (CCK) intraperitoneally (IP) at an interval of 1 h. PN50-treated animals received 1 mg/kg of PN50 IP 30 min before or after the CCK injections. The animals were sacrificed 4 h after the first injection of CCK.RESULTS: All the examined laboratory (the pancreatic weight/body weight ratio, serum amylase activity,pancreatic levels of TNF-α and IL-6, degree of lipid peroxidation, reduced glutathione levels, NF-κB binding activity, pancreatic and lung myeloperoxidase activity) and morphological parameters of the disease were improved before and after treatment with the PN50 peptide.According to the histological findings, PN50 protected the animals against acute pancreatitis by favoring the induction of apoptotic, as opposed to necrotic acinar cell death associated with severe acute pancreatitis.CONCLUSION: Our study implies that reversible inhibitors of stress-responsive transcription factors like NF-κB might be clinically useful for the suppression of the severity of acute pancreatitis.
基金supported by a grant from own resources of Medical University of Lublin
文摘BACKGROUND: There is a growing evidence that matrix metalloproteinase (MMP)-2 and MMP-9 (gelatinases) play an important role in the pathogenesis of numerous disorders especially with inflammatory etiology and extracellular matrix (ECM) remodeling. Despite the fact that gelatinases involve in liver cirrhosis is provided in the literature, their role in the pathogenesis of chronic pancreatitis and non-specific inflammatory bowel diseases is still under investigation.DATA SOURCES: We carried out a PubM ed search of English language articles relevant to the involvement of gelatinases in the pathogenesis of liver fibrosis, pancreatitis, and non-specific inflammatory bowel diseases.RESULTS: The decreased activity of gelatinases, especially MMP-2, is related to the development of liver fibrosis, probably due to the decrease of capability for ECM remodeling. Similar situation can be found in chronic pancreatitis; however reports on this matter are rare. The presence of non-specific inflammatory bowel diseases results in MMP-9 activity elevation.CONCLUSION: The fluctuation of gelatinases activity during liver fibrosis, chronic pancreatitis and non-specific inflammatorybowel diseases is observed, but the exact role of these enzymes demands further studies.
基金financially supported by the Scientific Research Foundation of State Education Ministry of China (Jiaowaisiliu[2008]890)Research Foundation of Education Department of Hebei Province of China(No. 2007132)
基金sapported by 3 months visiting fellowship (Ref.32402047975)from TWAS-UNESCO Associateship progranneIran National Science Foundation
文摘Objective:To justify the use of African mistletoe(AM) Viscum album {V.album) in folkoric medicine to treat diabetes.Methods:In one experiment,the fasting blood glucose(FBG) leveb of diabetic rats were monitored for 4 h.Diabetic rats were treated with AM at doses of 50 mg/kg(AM1) and 100 mg/kg(AM2),glibenclamide(GB)(positive control) and saline solution(SS).In another experiment,diabetic rats were treated with AM2,GB and SS daily for 3 weeks.Results:AM1 and AM2 elicited significant(P【0.05) hypoglycaemic effects within 4 h of extract administration. AM1 and AM2 decreased the FBG by 41%and 49%,respectively,at 2 h.AM2 was found to lower FBC by 51%,relative to baseline,which was comparable to GB at 3 h.In the second experiment, AM2 and GB significantly(P【0.05) decreased the FBG by 34%and 51%,respectively.This was followed by marked decrease in levels of HbAlC in AM2- and GB- treated diabetic rats.AM2 significantly(P【0.05) decreased the STZ-induced increase in levels of serum triglyceride,urea, lactate dehydrogenase,α-amylase and low-density lipoprotein-cholesterol.Furthermore, diabetic rats treated with AM2 had significanlly(P【0.05) elevated high-density lipoprotein-cholesterol. In contrast,STZ administration produced insignificant(P【0.05) effect on the levels of serum creatinine and total bilirubin.Conclusions:Extract of African mistletoe has anti-diabetic and anti-hyperlipidemic effects in STZ-diabetic rats.AM may find clinical application in the amelioration of diabetes-induced lipid disorders.
文摘Gastrointestinal diseases, specifically Crohn's disease, ulcerative colitis, diverticular disease, and primary biliary cirrhosis are all characterized by complicated inflammation of the digestive tract. Their pathology is multifactorial, and risk factors encompass both genetic and environmental factors. Recent advances in the genetic component of inflammatory bowel diseases(IBDs) have revealed that the tumor necrosis factor superfamily member 15(TNFSF15) contains a number of risk alleles associated not only with IBD but also with other diseases such as diverticular disease and primary biliary cirrhosis. These risk alleles in TNFSF15 and the altered expression of its gene product can serve as the common ground between these disorders by explaining at least some of the underlying processes that lead to a dysregulated immune response and subsequent chronic inflammation. Here, we aim to outline how the TNFSF15 gene is involved in the proliferation and cell fate of different populations of T cells and subsequently in the control of both pro-and anti-inflammatory cytokines. Furthermore, we summarize what is currently known of TNFSF15 control region variants, how they are associated with each mentioned disease, and how these variants can explain the autoimmune pathology of said diseases through altered TNFSF15 expression.
基金Supported by the "Mecenatura" grant of Debrecen University 3/1999 to K. P., and grants from the Hungarian Ministry of Health (ETT 41/2000 to I. A., and ETT 026/2003 to F. E.) from the Hungarian Science Research Fund (OTKA 043296 to F. E.).
文摘瞄准：在煽动性的肠疾病(IBD ) 学习内皮和可诱导的氮的氧化物 synthases (eNOS 和 i NOS ) 和他们的角色的表示。方法：我们检验了重量的单位的效果一在人的脐的静脉 endothelial (HUVEC ) 的功能和生存能力上与活跃 Crohn 的疾病(CD ) 和 ulcerative (UC ) 从病人获得了。HUVEC 面对与活跃 CD 或 UC 从病人包含健康控制，或浆液的分享的浆液的媒介为 0-48 h 是有教养的。eNOS 和 i NOS 的表示被免疫荧光设想，并且由西方的污点的测密度术确定了。增长活动被 Ki-67 免疫的计算机化的图象分析估计反应房间，并且也面对 NOS 禁止者测试了， 10 (-4) mol/L L 名字。Apoptosis 和坏死被 annexin-V-biotin 方法并且由分别地染色的 propidium 碘化物检验。结果：在 HUVEC 立即在到 UC 的暴露以后，浆液 eNOS 显著地被导致，在 12 h 到达一座山峰。相反，在 eNOS 的减少与 CD 重量的单位在孵化以后被观察一 eNOS 铺平的 and 在与控制(18%+/-16% 对 23%+/-15% P【0.01 ) 相比的 20 h 是最小的。UC 或 CD 浆液与控制相比在 i NOS 引起了重要增加(UC：300%+/-21% ；CD：275%+/-27% 对 108%+/-14% ， P【0.01 ) 。Apoptosis/necrosis 特征没在任何一个实验显著地不同。增加的增长活动与 L 名字面对 CD 浆液或术后疗法被检测。文化与 CD 浆液在 24 h 处理以后显示出像试管的形成。结论：IBD 重量的单位一在 eNOS/iNOS 的比率的唤起的变化，而没影响 HUVEC 的生存能力。这些同时包含了 eNOS 的下面规定和 i NOS 的起来规定，导致增加的增长活动并且可能 endothelial 的减少的反煽动性的保护。
文摘In this paper, we report the design and moleculardocking study of analogues of antimycin A3 as inhibitors of anti-apoptotic Bcl-2 of breast cancer. Twenty designed compounds and the original antimycin A3 were docked based on their interaction with breast tumor receptor binding target Bcl-2. The docking resulted in the five top-ranked compounds, namely, compounds 11, 14, 15, 16, and 20, which have a lower G binding energy, better affinity and stronger hydrogen bonding interactions to the active site of Bcl-2 than antimycin A3. Among those five top-ranked compounds, analogue compounds 11 and 14, which have an 18-membered tetralactone core and 18-membered tetraol core, respectively, exhibited the strongest hydrogen bond interaction, formed high stability conformation, and demonstrated the greatest inhibitory activity on the catalytic site of Bcl-2.
基金thanks to the Austrian grant(ASO)SK-06/07-14/2007the Faculty of Mediccine Research Fund(University of Pécs)AOK-KA-213/20.
文摘UV-VIS spectroscopic investigations of interaction of bovine and human serum albumin with selected chalcones (1) and their cyclic chalcone analogues: (E)-2-(4’-X-benzylidene-1-tetralones (3), benzosuberones (4) with dimethylamino and methoxy substituents and (E)-2-(2’,4’-dimethox- ybenzylidene)-1-indanone (2) were performed in polar respiration medium. Absorption maxima of the tested compounds were investigated in the presence of bovine and human serum albumin at the 0, 10, 30 and 60 minute timepoints of the interaction. The absorbance of all studied compounds in the presence of proteins decreased after one hour of the reaction. Molecule 4a showed the strongest and fastest kinet initial interaction with both albumins.
基金Financially supported from the Science Research Foundation of Shandong Entry-Exit InspectionQuarantine Bureau (No. SK201042)Weifang Medical University (No. KQ2007030)
文摘The title complex bis(2-acetylpyridine thiosemicarbazonato)-indium(iii) perchlo-rate hydrate has been synthesized by the reaction of 2-acetylpyridine thiosemicarbazide(L) with indium(iii) perchlorate,and its structure was characterized by elemental analysis,IR and single-crystal X-ray diffraction.The crystal of the title compound([In(C8H9N4S)2]ClO4·H2O) belongs to monoclinic,space group P21/c with a = 12.6438(18),b = 12.6259(18),c = 15.116(2) nm,β = 105.800(2)°,Z = 4,V = 2321.9(6) nm3,Mr = 618.79,Dc = 1.770 g/cm3,μ = 1.359 mm-1,F(000) = 1240,R = 0.0265 and wR = 0.0675.X-ray analysis indicates that various intriguing hydrogen patterns involving both the solvent intermedia and polyatomic counterions play crucial roles in the self-assembly of functional supramolecules.
文摘Each eukaryotic cell of multicellular organisms must be able to maintain its integrity by sensing both external and internal stimuli. The primary goal of the generated response mechanism is to drive back the system to the former or to a new homeostatic state. Moreover, the response has to provide an accurate survival-or-death decision to avoid any “misunderstanding” and its unwanted consequences. New data revealed that a systems-level crosstalk of molecular networks has an essential role in achieving the correct characteristic of the response. Although many molecular components of these processes already have been revealed, several elements and regulatory connections of crosstalk are still missing. These “gaps” of the complex control networks make hardly impossible to present comprehensive models. Therefore we approach the questions from a systems biology aspect by combining the experimental results with the special technique of mathematical modelling. In this short report we discuss some novel and preliminary data gained by this approach on the crosstalk between life and death decisions under cellular stress, to get a systems biological view of these networks.
文摘BACKGROUND The B.1.617.2(delta)variant of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was first discovered in Maharashtra in late 2020 and has rapidly expanded across India and worldwide.It took only 2 mo for this variant to spread in Indonesia,making the country the new epicenter of the delta variant as of July 2021.Despite efforts made by accelerating massive rollouts of current vaccines to protect against infection,cases of fully-vaccinated people infected with the delta variant have been reported.AIM To describe the demographic statistics and clinical presentation of the delta variant infection after the second dose of vaccine in Indonesia.METHODS A retrospective,single-centre case series of the general consecutive population that worked or studied at Faculty of Medicine,Universitas Indonesia with confirmed Delta Variant Infection after a second dose of vaccine from 24 June and 25 June 2021.Cases were collected retrospectively based on a combination of author recall,reverse transcription-polymerase chain reaction(RT-PCR),and whole genome sequencing results from the Clinical Microbiology Laboratory,Faculty of Medicine,Universitas Indonesia.RESULTS Between 24 June and 25 June 2021,15 subjects were confirmed with the B.1.617.2(delta)variant infection after a second dose of the vaccine.Fourteen subjects were vaccinated with CoronaVac(Sinovac)and one subject with ChAdOx1 nCoV-19(Oxford-AstraZeneca).All of the subjects remained in home isolation,with fever being the most common symptom at the onset of illness(n=10,66.67%).The mean duration of symptoms was 7.73 d(±5.444).The mean time that elapsed from the first positive swab to a negative RT-PCR test for SARS-CoV-2 was 17.93 d(±6.3464).The median time that elapsed from the second dose of vaccine to the first positive swab was 87 d(interquartile range:86-128).CONCLUSION Although this case shows that after two doses of vaccine,subjects are still susceptible to the delta variant infection,currently available vaccines remain the most effective protection.They reduce clinical manifestations of COVID-19,decrease recovery time from the first positive swab to negative swab,and lower the probability of hospitalization and mortality rate compared to unvaccinated individuals.
基金supported by the Austrian Science and Research Liaison Office(ASO)grant,the VEGA 1/0999/11 grant；the Faculty of Medicine Research Fund(PTE AOK-KA-2013/20),(University of Pécs).
文摘Interaction of the synthetic chalcones (1b,1c) and their cyclic analogues (2b,2c) with bovine (BSA) and human serum albumin (HSA) as well as with rat liver mitochondria (RLM) was studied by fluorescence spectroscopy. The maxima of emission fluorescence spectra were changed only in the case of 2b and 2c during interaction with BSA, HSA as well as mitochondrial outer membrane showing a slight hypsochromic shift and decrease of fluorescence. Interaction of the methoxy-(1b,2b) and the dimethylamino-substituted (1c,2c) compounds with outer mitochondrial membrane were studied by fluorescence polarization. Fluorescence polarization of 1b in the presence of the two proteins and mitochondria was found to be unchanged. Under similar conditions (2b,1c,2c) showed continuously increasing fluorescence polarization signal during the 30 minute period of investigations. Since fluorescence polarization supposes that as a result of binding these substances to proteins and lipids. Compound 2c displayed a continuous increase of fluorescence polarization signal in the presence of proteins (BSA, HSA), yeast cytoplasm (YC) and mitochondria (YM and RLM). This compound displayed a significant cytotoxic effect. This pattern of interaction with proteins might be one of the contributing vectors of the observed cytotoxicity against several human carcinoma cell lines.
文摘Background: Mutations in the RPGR gene are associated with rod-cone or cone-rod dystrophy, the latter associated with mutations at the distal end. Cone-rod dystrophy (CRD) is a subgroup of hereditary retinal disorders characterized by the primary degeneration of cone photoreceptors often followed by progressive loss of rod photoreceptors in the peripheral visual field. Purpose: The aim of this study was to describe the milder CRD phenotype associated with a novel pathogenic variant c.1905 + 223C > T (p.Q710X) found in RPGR which results in shortening of the photoreceptor specific isoform RPGR <sup>ORF15</sup>. Method: An 11-year-old boy with symptoms of CRD and two female relatives were referred for detailed ophthalmic examinations. Genetic testing was performed by next-generation sequencing of clinical exome followed by Sanger sequencing for segregation analysis. Results: Genetic analysis identified a novel variant in ORF15 of the RPGR gene (c.1905 + 223C > T, p.Q710X) in the proband considered as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) standards. Segregation study identified the mutation in a heterozygous state in the mother and her sister. Detailed ophthalmological examination revealed slightly reduced color vision and scattered grayish point-like deposits in the posterior pole of the fundus in the male patient. All mutation carriers were myopic. Conclusion: We report a novel pathogenic RPGR variant in a Bulgarian patient with clinical features compatible with the CRD diagnosis. This condition is inherited as an X-linked dominant trait in its familial form presenting with a mild CRD phenotype in the male hemizygous proband and a moderate to high myopia in the female heterozygous carriers.
基金Project of Young Teachers’Research Fund of Xinyang College of Agriculture and Forestry(Project number:QN2021014)。
文摘The integration of the civics course and surveying professional course is an important part of the teaching reform of surveying,which is an important way to implement the principle of cultivating educated talents with moral characters for the country.Based on the surveying course,this paper deeply analyses the spirit of hard work and endurance,craftsmanship,innovation,and national sentiment contained in surveying,carries the civics education with professional knowledge,and makes the civics element subliminally enter the brain and heart,so as to improve the patriotic sentiment and professional quality of students.
文摘Colorectal cancer(CRC) is fourth most common cancer in men and third in women worldwide. Developing a diagnostic panel of sensitive and specific biomarkers for the early detection of CRC is recognised as to be crucial for early initial diagnosis, which in turn leads to better long term survival. Most of the research on novel potential CRC biomarkers in the last 2 decades has been focussed on stool DNA analysis. In this paper, we describe the recent advances in non-invasive CRC screening and more specifically in molecular assays for aberrantly methylated BMP3 and NDRG4 promoter regions. In several research papers these markers showed superior rates for sensitivity and specificity in comparison to previously described assays. These tests detected the majority of adenomas ≥ 1 cm in size and the detection rates progressively increased with larger adenomas. The methylation status of the BMP3 and NDRG4 promoters demonstrated effective detection of neoplasms at all sites throughout the colon and was not affected by common clinical variables. Recently, a multitarget stool DNA test consisting of molecular assays for aberrantly methylated BMP3 and NDRG4 promoter regions, mutant KRAS and immunochemical assay for human haemoglobin has been made commercially available and is currently reimbursed in the United States. Although this is the most sensitive noninvasive CRC screening test, there is the need for further research in several areas- establishment of the best timeframe for repeated DNA stool testing; validation of the results in populations outside of North America; usefulness for surveillance and prognosis of patients; cost-effectiveness of DNA stool testing in real-life populations.
基金Supported by Hungarian Scientific Research Fund(OTKA 104113 and 106060)the Hungarian Research and Technological Innovation Fund(KMR_12-1-2012-0074)
文摘Obesity due to excessive food intake and the lack of physical activity is becoming one of the most serious public health problems of the 21stcentury. With the increasing prevalence of obesity, non-alcoholic fatty liver disease is also emerging as a pandemic. While previously this pathophysiological condition was mainly attributed to triglyceride accumulation in hepatocytes,recent data show that the development of oxidative stress, lipid peroxidation, cell death, inflammation and fibrosis are mostly due to accumulation of fatty acids,and the altered composition of membrane phospholipids. In fact, triglyceride accumulation might play a protective role, and the higher toxicity of saturated or trans fatty acids seems to be the consequence of a blockade in triglyceride synthesis. Increased membrane saturation can profoundly disturb cellular homeostasis by impairing the function of membrane receptors,channels and transporters. However, it also inducesendoplasmic reticulum stress via novel sensing mechanisms of the organelle's stress receptors. The triggered signaling pathways in turn largely contribute to the development of insulin resistance and apoptosis. These findings have substantiated the lipotoxic liver injury hypothesis for the pathomechanism of hepatosteatosis.This minireview focuses on the metabolic and redox aspects of lipotoxicity and lipoapoptosis, with special regards on the involvement of endoplasmic reticulum stress responses.
基金the postdoctoral fellowship of the Hungarian Ministry of Educationthe National Research Foundations (OTKA) grants T30735,T042589 and TS049817
文摘AIM: To establish the therapeutic potential of proteasome inhibition, we examined the therapeutic effects of MG132 (Z-Leu-Leu-Leu-aldehyde) in an experimental model of acute pancreatitis.METHODS: Pancreatitis was induced in rats by two hourly intraperitoneal (ip) injections of cholecystokinin octapeptide (CCK; 2 x 100 μg/kg) and the proteasome inhibitor MG132 (10 mg/kg ip) was administered 30 min after the second CCK injection. Animals were sacrificed 4 h after the first injection of CCK.RESULTS: Administering the proteasome inhibitor MG132 (at a dose of 10 mg/kg, ip) 90 min after the onset of pancreatic inflammation induced the expression of cell-protective 72 kDa heat shock protein (HSP72) and decreased DNA-binding of nuclear factor-kB (NF-kB). Furthermore MG132 treatment resulted in milder inflammatory response and cellular damage, as revealed by improved laboratory and histological parameters of pancreatitis and associated oxidative stress.CONCLUSION: Our findings suggest that proteasome inhibition might be beneficial not only for the prevention, but also for the therapy of acute pancreatitis.
基金Supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences to Csala M
文摘The metabolic syndrome, one of the most common clinical conditions in recent times, represents a combination of cardiometabolic risk determinants, including central obesity, glucose intolerance, insulin resistance, dyslipidemia, non-alcoholic fatty liver disease and hypertension. Prevalence of the metabolic syndrome is rapidly increasing worldwide as a consequence of common overnutrition and consequent obesity. Although a unifying picture of the pathomechanism is still missing, the key role of the pre-receptor glucocorticoid activation has emerged recently. Local glucocorticoid activation is catalyzed by a triad composed of glucose-6-phosphate-transporter, hexose-6-phosphate dehydrogenase and 11β-hydroxysteroid dehydrogenase type 1 in the endoplasmic reticulum. The elements of this system can be found in various cell types, including adipocytes and hepatocytes. While the contribution of glucocorticoid activation in adipose tissue to the pathomechanism of the metabolic syndrome has been well established, the relative importance of the hepatic process is less understood. This review summarizes the available data on the role of the hepatic triad and its role in the metabolic syndrome, by confronting experimental findings with clinical observations.
文摘Diabetic neuropathy is one of the most serious complications of diabetes, and its increase shows no sign of stopping. Furthermore, current clinical treatments do not yet approach the best effectiveness. Thus, the development of better strategies for treating diabetic neuropathy is an urgent matter. In this review, we first discuss the advantages and disadvantages of some major mouse models of diabetic neuropathy and then address the targets for mechanism-based treatment that have been studied. We also introduce our studies on each part. Using stem cells as a source of neurotrophic factors to target extrinsic factors of diabetic neuropathy, we found that they present a promising treatment.
