Alzheimer's disease(AD),the most common form of neurodegeneration,is characterized by selective neuronal vulnerability and brain regionselective neuron demise.The entorhinal cortex and hippoc,ampal CA1 projection ...Alzheimer's disease(AD),the most common form of neurodegeneration,is characterized by selective neuronal vulnerability and brain regionselective neuron demise.The entorhinal cortex and hippoc,ampal CA1 projection neurons are at greater risk in AD whereas other regions display resistance to neurodegeneration.Interestingly,the cerebellum,a phylogenetically very old region,is affected only very late in the disease progression.展开更多
Medically assisted reproduction(MAR)techniques are highly dependent on the sperm quantity and quality.Low sperm concentrations can be bypassed at least to some point by the usage of more sophisticated MAR techniques l...Medically assisted reproduction(MAR)techniques are highly dependent on the sperm quantity and quality.Low sperm concentrations can be bypassed at least to some point by the usage of more sophisticated MAR techniques like intracytoplasmic sperm injection(ICSI).Compared to this,disruptions in established indicators of sperm quality like motility or morphology pose greater challenges for the therapy of couple infertility.展开更多
Recently,high-entropy materials are attracting enormous attention in battery applications,encompassing both electrode materials and solid electrolytes,due to the pliability and diversification in material composition ...Recently,high-entropy materials are attracting enormous attention in battery applications,encompassing both electrode materials and solid electrolytes,due to the pliability and diversification in material composition and electronic structure.Theoretically,the rapid ion transport and the abundance of surface defects in high-entropy materials suggest a potential for enhancing the performance of composite solid-state electrolytes(CPEs).Herein,using a high-entropy oxide(HEO)filler to assess its potential contributions to CPEs is proposed.The distinctive structural distortions in HEO significantly improve the ionic conductivity(5×10^(−4) S·cm^(−1) at 60℃)and Li-ion transference number(0.57)of CPEs.Furthermore,the enhanced Li-ion transport capability extends the critical current density from 0.6 to 1.5 mA·cm^(−2) in Li/Li symmetric cells.In addition,all-solid-state batteries incorporating the HEO-modified CPEs exhibit superior rate performance and cycling stability.The work will enrich the application of HEOs in CPEs and provide fundamental understanding.展开更多
BACKGROUND Botulinum toxin(BoNT)is a bacterial poison that acts by blocking the release of acetylcholine-containing vesicles at the neuromuscular junction.Notably,a mild amount of BoNT is known to exert therapeutic be...BACKGROUND Botulinum toxin(BoNT)is a bacterial poison that acts by blocking the release of acetylcholine-containing vesicles at the neuromuscular junction.Notably,a mild amount of BoNT is known to exert therapeutic benefits against various diseases,including migraine,movement disorders,anxiety and neurocognitive deficits.BoNT treatment appears to increase platelet count in circulation.Therefore,BoNT treatment may be associated with the regulation of blood coagulation upon haemorrhagic events.However,the effects of BoNT on the degree of bleeding and clotting events have not yet been determined.AIM To investigate the effect of BoNT on the bleeding parameters and blood coagulation events in experimental mice.METHODS A group of 7-8-month-old mice was intramuscularly injected with a mild single dose of BoNT.After a month of BoNT injection,animals were subjected to tail bleeding assay,assessment of clotting time,and degree of platelet aggregation in comparison with the control group.RESULTS Results revealed that BoNT injection significantly reduced blood loss and bleeding time in experimental aging mice upon tail tip transection.Moreover,the blood samples collected from the BoNT-treated mice showed enhanced platelet aggregation and intense formation of the fibrin clot compared to the control.This study indicates a putative therapeutic value of BoNT in mitigating bleeding episodes,possibly through its platelet-enhancing property.CONCLUSION BoNT treatment effectively facilitates blood coagulation.Upon further validation,this approach can be translated to treat traumatic blood vessel injuries,haemorrhagic diseases,and bleeding complications associated with surgical procedures.展开更多
Interlayer interactions in bilayer or multilayer electron systems have been studied extensively,and many exotic physical phenomena have been revealed.However,systematic investigations of the impact of interlayer inter...Interlayer interactions in bilayer or multilayer electron systems have been studied extensively,and many exotic physical phenomena have been revealed.However,systematic investigations of the impact of interlayer interactions on magnonic physics are very few.Here,we use a van derWaals(vdW)honeycomb heterostructure as a platform to investigate the modulation of magnon properties in honeycomb AA-and AB-stacking heterostructures with ferromagnetic and antiferromagnetic interlayer interactions,including topological phases and thermal Hall conductivity.Our results reveal that interlayer interactions play a crucial role in modulating the magnonic topology and Hall transport properties of magnetic heterostructures,with potential for experimental realization.展开更多
Background:Cardiovascular disease remains the leading cause of mortality across the European region.Despite marked regional variations,cross-national differences in underlying risk factors have received comparatively ...Background:Cardiovascular disease remains the leading cause of mortality across the European region.Despite marked regional variations,cross-national differences in underlying risk factors have received comparatively little attention.Objective:To use European Social Survey,a unique cross-European dataset,to examine regional patterns in prevalence and lifestyle risks.Methods:This study employs clustering analysis and nested logistic modelling.Counterfactual analysis was conducted to illustrate how lifestyle modifications could reduce risk.Results:The prevalence of heart problems was highest in Latvia(25.6%,95%CI:23.0 to 28.2),Lithuania(17.6%,95%CI:15.5 to 19.7),and Bulgaria(14.9%,95%CI:13.4 to 19.4).Regionally,heart problems were higher in Northern and Eastern Europe(15%and 11.9%)than Western and Southern Europe(10.8%and 9.5%).Among the risk factors,modelling emphasised the importance of modifiable factors including education,body mass index and physical activity.Conclusion:The results underline that cardiovascular disease is influenced by interrelated socioeconomic,environmental and lifestyle determinants.Public policy interventions could be targeted at those countries where greatest reductions are obtainable and concentrate on interventions on those lifestyle traits identified.The study utilised a social science dataset,thereby illustrating how multidisciplinary resources can benefit epidemiological research.展开更多
In ethnopharmacology, and especially in traditional Chinese medicine, medicinal plants have been used for thousands of years. Similarly, agricultural plants have been used throughout the history of mankind. The recent...In ethnopharmacology, and especially in traditional Chinese medicine, medicinal plants have been used for thousands of years. Similarly, agricultural plants have been used throughout the history of mankind. The recent development of the genetic engineering of plants to produce plants with desirable features adds a new and growing dimension to humanity’s usage of plants. The biotechnology of plants has come of age and a plethora of bioengineering applications in this context have been delineated during the past few decades. Callus cultures and suspension cell cultures offer a wide range of usages in pharmacology and pharmacy (including Chinese medicine), as well as in agriculture and horticulture. This review provides a timely overview of the advancements that have been made with callus cultures in these scientific fields. Genetically modified callus cultures by gene technological techniques can be used for the synthesis of bioactive secondary metabolites and for the generation of plants with improved resistance against salt, draft, diseases, and pests. Although the full potential of callus plant culture technology has not yet been exploited, the time has come to develop and market more callus culture-based products.展开更多
AIM： To analyze the relevance of the microRNA miR-196a for colorectal oncogenesis.METHODS： The impact of miR-196a on the restriction targets HoxA7, HoxBS, HoxC8 and HoxD8 was analyzed by reverse transcription polyme...AIM： To analyze the relevance of the microRNA miR-196a for colorectal oncogenesis.METHODS： The impact of miR-196a on the restriction targets HoxA7, HoxBS, HoxC8 and HoxD8 was analyzed by reverse transcription polymerase chain reaction（RT-PCR） after transient transfection of SW480 cancer cells. The miR-196a transcription profile in colorectalcancer samples, mucosa samples and diverse cancercell lines was quantified by RT-PCR. Transiently miR-196a-transfected colorectal cancer cells were used for diverse functional assays in vitro and for a xenograft lung metastasis model in vivo.RESULTS： HoxA7, HoxB8, HoxC8 and HoxD8 wererestricted by miR-196a in a dose-dependent andgene-specific manner. High levels of miR-196aactivated the AKT signaling pathway as indicated byincreased phosphorylation of AKT. In addition, highlevels of miR-196a promoted cancer cell detachment,migration, invasion and chemosensitivity towardsplatin derivatives but did not impact on proliferationor apoptosis. Furthermore, miR-196a increased thedevelopment of lung metastases in mice after tail veininjection.展开更多
The completely assembled human genome has made it possible for modern medicine to step into an era rich in genetic information and high-throughput genomic analysis. These novel and readily available genetic resources ...The completely assembled human genome has made it possible for modern medicine to step into an era rich in genetic information and high-throughput genomic analysis. These novel and readily available genetic resources and analytical tools may be the key to unravel the molecular basis of hepatocellular carcinoma (HCC). Moreover, since an efficient treatment for this disease is lacking, further understanding of the genetic background of HCC will be crucial in order to develop new therapies aimed at selected targets. We report on the current status and recent developments in HCC genetics. Special emphasis is given to the genetics and regulation of major signalling pathways involved in HCC such as p53, Wnt- signalling, TGFβ, Ras, and Rb pathways. Furthermore, we describe the influence of chromosomal aberrations as well as of DNA methylation. Finally, we report on the rapidly developing field of genomic expression profiling in HCC, mainly by microarray analysis.展开更多
Carcinomas of the stomach and gastroesophageal junction are among the five top leading cancer types worldwide. In spite of radical surgical R0 resections being the basis of cure of gastric cancer, surgery alone provid...Carcinomas of the stomach and gastroesophageal junction are among the five top leading cancer types worldwide. In spite of radical surgical R0 resections being the basis of cure of gastric cancer, surgery alone provides long-term survival in only 30% of patients with advanced International Union Against Cancer （UICC） stages in Western countries because of the high risk of recurrence and metachronous metastases. However, recent large phase-Ⅲ studies improved the diagnostic and therapeutic options in gastric cancers, indicating a more multidisciplinary management of the disease. Multimodal strategies combining different neoadjuvant and/or adjuvant protocols have clearly improved the gastric cancer prognosis when combined with surgery with curative intention. In particular, the perioperative （neoadjuvant, adjuvant） chemotherapy is now a well-established new standard of care for advanced tumors. Adjuvant therapy alone should be carefully discussed after surgical resection, mainly in individual patients with large lymph node positive tumors when neoadjuvant therapy could not be done. The palliative treatment options have also been remarkably improved with new chemotherapeutic agents and will further be enhanced with targeted therapies such as different monoclonal antibodies. This article reviews the most relevant literature on the multidisciplinary management of gastric and gastroesophageal cancer, and discusses future strategies toimprove Iocoregional failures.展开更多
AIM:To gain mechanistic insights into the role played by epidermal growth factor receptor (EGFR) in the regulation of vascular endothelial growth factors (VEGFs) in colorectal cancer (CRC). METHODS:The impact of high-...AIM:To gain mechanistic insights into the role played by epidermal growth factor receptor (EGFR) in the regulation of vascular endothelial growth factors (VEGFs) in colorectal cancer (CRC). METHODS:The impact of high-level expression of the growth factor receptors EGFR and VEGF receptor (VEGFR)3 and the VEGFR3 ligands VEGF-C and VEGF-D on disease progression and prognosis in human CRC was investigated in 108 patients using immunohistochemistry. Furthermore, the expression of the lymphangiogenic factors in response to the modulation of EGFR signalling by the EGFR-targeted monoclonal antibody cetuximab was investigated at the mRNA and protein level in human SW480 and SW620 CRC cell lines and a mouse xenograft model. RESULTS: Human CRC specimens and cell lines displayed EGFR, VEGF-C and VEGF-D expression with varying intensities. VEGF-C expression was associated with histological grade. Strong expression of VEGF-D was significantly associated with lymph node metastases and linked to a trend for decreased survival in lymph node-positive patients. EGFR blockade with cetuximab resulted in a significant decrease of VEGF-D expression in vitro and in vivo. CONCLUSION:In conclusion, the expression of VEGF-D in colorectal tumours is significantly associated with lymphatic involvement in CRC patients and such expression might be blocked effectively by cetuximab.展开更多
To review the implication of CXCR4 for gastrointestinal cancer, a ＂Pubmed＂ analysis was performed in order to evaluate the relevance of CXCR4 and its ligands for gastrointestinal cancers. Search terms applied were ...To review the implication of CXCR4 for gastrointestinal cancer, a ＂Pubmed＂ analysis was performed in order to evaluate the relevance of CXCR4 and its ligands for gastrointestinal cancers. Search terms applied were ＂cancer, malignoma, esophageal, gastric, colon, colorectal, hepatic, pancreatic, CXCR4, SDF- 1α, and SDF-1β＂. CXCR4 expression correlated with dissemination of diverse gastrointestinal malignomas. The CXCR4 ligand SDF-1α might act as ＂chemorepellent＂ while SDF-1β might act as ＂chemorepellent＂ for CTLs, inducing tumor rejection. The paracrine expression of SDF-1α was furthermore closely associated with neoangiogenesis. CXCR4 and its ligands influence the dissemination, immune rejection, and neoangiogenesis of human gastrointestinal cancers. Inhibition of CXCR4 might be an interesting therapeutic option.展开更多
AIM： To define the （co-）expression pattern of target receptor-tyrosine-kinases （RTK） in human gastric adenocarcinoma. METHODS： The （co-）expression pattern of VEGFR1-3, PDGFR（α/β and EGFR1 was analyzed by RT...AIM： To define the （co-）expression pattern of target receptor-tyrosine-kinases （RTK） in human gastric adenocarcinoma. METHODS： The （co-）expression pattern of VEGFR1-3, PDGFR（α/β and EGFR1 was analyzed by RT-PCR in 51 human gastric adenocarcinomas. In addition, IHC staining was applied for confirmation of expression and analysis of RTK localisation. RESULTS： The majority of samples revealed a VEGFR1 （98%）, VEGFR2 （80%）, VEGFR3 （67%）, PDGFRα （82%） and PDGFRβ （82%） expression, whereas only 62% exhibited an EGFR1 expression. 78% of cancers expressed at least four out of six RTKs. While VEGFR1-3 and PDGFRα revealed a predominantly cytoplasmatic staining in tumor cells, accompanied by an additional nuclear staining for VEGFR3, EGFR1 was almost exclusively detected on the membrane of tumor cells. PDGFRβ was restricted to stromal pericytes, which also depicted a PDGFRα expression. CONCLUSION： Our results reveal a high rate ofreceptor-tyrosine-kinases coexpression in gastric adenocarcinoma and might therefore encourage an application of multiple-target RTK-inhibitors within a combination therapy.展开更多
AIM: To evaluate and confirm the low incidence of hepatocellular carcinoma (HCC) in patients with autoimmune hepatitis (AIH). At present only very few cases of HCC in patients with AIH and definite exclusion of chroni...AIM: To evaluate and confirm the low incidence of hepatocellular carcinoma (HCC) in patients with autoimmune hepatitis (AIH). At present only very few cases of HCC in patients with AIH and definite exclusion of chronic viral hepatitis have been published, suggesting that HCC due to AIH is rare. METHODS: In order to further investigate the incidence of HCC in patients with AIH, we reviewed our large cohort of 278 patients with AIH. RESULTS: Eighty-nine patients (32%) were diagnosed with liver cirrhosis, a preneoplastic condition for HCC. We studied a total of 431 patient years of cirrhosis in these patients, an average 4.8 years per patient. During this period none of the patients of our own study cohort developed HCC. However, three patients with HCC due to AIH associated liver cirrhosis were referred to our department for further treatment of HCC. In all three patients chronic viral hepatitis was excluded. CONCLUSION: We conclude that HCC may under rare circumstances develop due to chronic AIH dependent liver cirrhosis. Compared to other causes of liver cirrhosis such as chronic viral hepatitis, alcohol, or hemochromatosis, the incidence of HCC is significantly lower. Pathophysiological differences between AIH and chronic viral hepatitis responsible for differences in the incidence of HCC are yet to be further characterized and may lead to new therapeutic concepts in prevention and treatment of liver cancer.展开更多
The aim of this study was to investigate the physiological foramen diameter, shape and distance between physiological and anatomical apex of maxillary and mandibular first and second molars. Accurate knowledge of the ...The aim of this study was to investigate the physiological foramen diameter, shape and distance between physiological and anatomical apex of maxillary and mandibular first and second molars. Accurate knowledge of the physiological foramina morphology; thus, inherent mechanical shaping technical hindrances, is decisive when taking the corresponding root canal final preparation decision. The morphological dimensions of a total of 1 727 physiological foramina were investigated by means of micro-computed tomography. Mean narrow and wide （to a high number, oval） diameters of the physiological foramen were 0.24, 0.22 and 0.33 mm and 0.33, 0.31 and 0.42 mm in mesiobuccal （MB）, distobuccal （DB） and palatal （P） roots in maxillary first molars; 0.24, 0.22 and 0.33 mm and 0.41, 0.33 and 0.44 in MB, DB, and P roots in maxillary second molars. Mandibular first molars showed mean narrow and wide diameters of 0.24 and 0.30 mm and of 0.39 and 0.46 mm in mesial （M） and distal （D） roots; second mandibular molars showed 0.25 and 0.31 mm and 0.47 mm in M and D roots. The mean distance between the physiological foramina and anatomical apex was 0.82, 0.81 and 1.02 mm and 0.54, 0.43 and 0.63 mm in MB, DB and P roots of the maxillary first and second molars, respectively. A mean distance of 0.95 mm （M） and 1.05 mm （D） in the first and 0.78 mm （M） and 0.81 mm （D） in the second mandibular molars was observed. Based on the results obtained, assumable recommendations for final preparation size of the physiological foramen were calculated. However, when taking into consideration, the resulting standard deviations of marginal errors must be cautiously considered when taking a final decision in clinical endodontic treatment.展开更多
Schwann cells,the myelinating glia of the peripheral nervous system,wrap axons multiple times to build their myelin sheath.Myelin is of paramount importance for axonal integrity and fast axon potential propagation.How...Schwann cells,the myelinating glia of the peripheral nervous system,wrap axons multiple times to build their myelin sheath.Myelin is of paramount importance for axonal integrity and fast axon potential propagation.However,myelin is lacking or dysfunctional in several neuropathies including demyelinating and dysmyelinating Charcot-M arie-To oth disease.Charcot-Marie-To oth disease represents the most prevalent inherited neuropathy in humans and is classified either as axonal,demyelinating or dysmyelinating,or as intermediate.The demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease constitute the majority of the disease cases and are most frequently due to mutations in the three following myelin genes:peripheral myelin protein 22,myelin protein ze ro and gap junction beta 1(coding for Connexin 32) causing Charcot-M arie-Tooth disease type 1A,Charcot-Marie-Tooth disease type 1B,and X-linked Charcot-M arie-Tooth disease type 1,respectively.The resulting perturbation of myelin structure and function leads to axonal demyelination or dysmyelination and causes severe disabilities in affected patients.No treatment to cure or slow down the disease progression is currently available on the market,howeve r,scientific discoveries led to a better understanding of the pathomechanisms of the disease and to potential treatment strategies.In this review,we describe the features and molecular mechanisms of the three main demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease,the rodent models used in research,and the emerging therapeutic approaches to cure or counteract the progression of the disease.展开更多
Artemisinin,a constituent of Artemisia annua L.,is a well-known antimalarial drug.Artemisinin-type drugs also inhibit cancer growth in vitro and in vivo.Herbal extracts of A.annua inhibit the growth of cancer cell lin...Artemisinin,a constituent of Artemisia annua L.,is a well-known antimalarial drug.Artemisinin-type drugs also inhibit cancer growth in vitro and in vivo.Herbal extracts of A.annua inhibit the growth of cancer cell lines.Here,we report on the use of capsules containing powder of Herba Artemisiae annuae to treat pet sarcoma.The surgical tumor removal as standard treatment was supplemented by adjuvant therapy with A.annua.One cat and one dog with fibrosarcoma survived 40 and 37 months,respectively,without tumor relapse.Two other dogs suffering from fibrosarcoma and hemangioendothelial sarcoma also showed complete remission and are still alive after 39 and 26 months,respectively.A.annua was well tolerated without noticeable side effects.These four cases indicate that A.annua may be a promising herbal drug for cancer therapy.展开更多
AIM： To study, whether the association of Schatzki rings with other esophageal disorders support one of the theories about its etiology. METHODS： From 1987 until 2007, all patients with newly diagnosed symptomatic S...AIM： To study, whether the association of Schatzki rings with other esophageal disorders support one of the theories about its etiology. METHODS： From 1987 until 2007, all patients with newly diagnosed symptomatic Schatzki rings （SRs） were prospectively registered and followed. All of them underwent structured interviews with regards to clinical symptoms, as well as endoscopic and/or radiographic examinations. Endoscopic and radiographic studies determined the presence of an SR and additional morp- hological abnormalities. RESULTS： One hundred and sixty-seven patients （125 male, 42 female） with a mean age of 57.1±14.6 years were studied. All patients complained of intermittent dysphagia for solid food and 113 （79.6%） patients had a history of food impaction. Patients experienced symptoms for a mean of 4.7± 5.2 years before diagnosis. Only in 23.4% of the 64 patients who had endoscopic and/or radiological examinations before their first presentation to our clinic, was the SR previously diagnosed. At presentation, the mean ring diameter was 13.9 4- 4.97 mm. One hundred and sixty-two （97%） patients showed a sliding hiatal hernia. Erosive reflux esophagitis was found in 47 （28.1%） patients. Twenty-six （15.6%） of 167 patients showed single or multiple esophageal webs; five （3.0%） patients exhibited eosinophilic esophagitis; and four （2.4%） had esophageal diverticula. Four （7%） of 57 patients undergoing esophageal manometry had non- specific esophageal motility disorders. CONCLUSION： Schatzki rings are frequently associated with additional esophageal disorders, which support the assumption of a multifactorial etiology. Despite typical symptoms, SRs might be overlooked.展开更多
Parkinson's disease(PD) is one of the most common neurodegenerative diseases,affecting individuals especially over 60 years of age.In the next three decades,more than 12 million people will suffer from PD worldwid...Parkinson's disease(PD) is one of the most common neurodegenerative diseases,affecting individuals especially over 60 years of age.In the next three decades,more than 12 million people will suffer from PD worldwide(Rocca,2018).The characteristic symptoms of PD begin as a movement disorder including bradykinesia,resting tremor,rigidity,and postural instability.展开更多
基金supported by a grant of the Deutsche Forschungsgemeinschaft(DFGCRC1177 and joint DFG/ANR grant)(to CB)a fellowship of the Deutscher Akademischer Austauschdienst(DAAD)(to TNMP)。
文摘Alzheimer's disease(AD),the most common form of neurodegeneration,is characterized by selective neuronal vulnerability and brain regionselective neuron demise.The entorhinal cortex and hippoc,ampal CA1 projection neurons are at greater risk in AD whereas other regions display resistance to neurodegeneration.Interestingly,the cerebellum,a phylogenetically very old region,is affected only very late in the disease progression.
文摘Medically assisted reproduction(MAR)techniques are highly dependent on the sperm quantity and quality.Low sperm concentrations can be bypassed at least to some point by the usage of more sophisticated MAR techniques like intracytoplasmic sperm injection(ICSI).Compared to this,disruptions in established indicators of sperm quality like motility or morphology pose greater challenges for the therapy of couple infertility.
基金supported by the National Natural Science Foundation of China(No.52002094)Shenzhen Science and Technology Program(Nos.JCYJ20210324121411031,JSGG202108021253804014 and RCBS20210706092218040)Shenzhen Steady Support Plan(Nos.GXWD20221030205923001 and GXWD20201230155427003-20200824103000001).
文摘Recently,high-entropy materials are attracting enormous attention in battery applications,encompassing both electrode materials and solid electrolytes,due to the pliability and diversification in material composition and electronic structure.Theoretically,the rapid ion transport and the abundance of surface defects in high-entropy materials suggest a potential for enhancing the performance of composite solid-state electrolytes(CPEs).Herein,using a high-entropy oxide(HEO)filler to assess its potential contributions to CPEs is proposed.The distinctive structural distortions in HEO significantly improve the ionic conductivity(5×10^(−4) S·cm^(−1) at 60℃)and Li-ion transference number(0.57)of CPEs.Furthermore,the enhanced Li-ion transport capability extends the critical current density from 0.6 to 1.5 mA·cm^(−2) in Li/Li symmetric cells.In addition,all-solid-state batteries incorporating the HEO-modified CPEs exhibit superior rate performance and cycling stability.The work will enrich the application of HEOs in CPEs and provide fundamental understanding.
基金Supported by The Science and Engineering Research Board,No.SERB-EEQ/2016/000639The University Grants Commission-Faculty Recharge Programme(UGC-FRP),No.F4-5(97)/2014+2 种基金Rashtriya Uchchatar Shiksha Abhiyan(RUSA)2.0,Biological Sciences,Bharathidasan University,No.TN RUSA:311/RUSA(2.0)/2018Infrastructure of the Department of Animal Science,Bharathidasan University,UGC-SAP-DRS and DST-FISTand CSIR-SRF Direct,No.09/0475(23353)/2025-EMR-I.
文摘BACKGROUND Botulinum toxin(BoNT)is a bacterial poison that acts by blocking the release of acetylcholine-containing vesicles at the neuromuscular junction.Notably,a mild amount of BoNT is known to exert therapeutic benefits against various diseases,including migraine,movement disorders,anxiety and neurocognitive deficits.BoNT treatment appears to increase platelet count in circulation.Therefore,BoNT treatment may be associated with the regulation of blood coagulation upon haemorrhagic events.However,the effects of BoNT on the degree of bleeding and clotting events have not yet been determined.AIM To investigate the effect of BoNT on the bleeding parameters and blood coagulation events in experimental mice.METHODS A group of 7-8-month-old mice was intramuscularly injected with a mild single dose of BoNT.After a month of BoNT injection,animals were subjected to tail bleeding assay,assessment of clotting time,and degree of platelet aggregation in comparison with the control group.RESULTS Results revealed that BoNT injection significantly reduced blood loss and bleeding time in experimental aging mice upon tail tip transection.Moreover,the blood samples collected from the BoNT-treated mice showed enhanced platelet aggregation and intense formation of the fibrin clot compared to the control.This study indicates a putative therapeutic value of BoNT in mitigating bleeding episodes,possibly through its platelet-enhancing property.CONCLUSION BoNT treatment effectively facilitates blood coagulation.Upon further validation,this approach can be translated to treat traumatic blood vessel injuries,haemorrhagic diseases,and bleeding complications associated with surgical procedures.
基金supported by the National Natural Science Foundation of China(Grant Nos.12404051,12347156,12174157,12074150,and 12174158)the National Key Research and Development Program of China(Grant No.2022YFA1405200)+2 种基金the Natural Science Foundation of Jiangsu Province(Grant No.BK20230516)the Scientific Research Project of Jiangsu University(Grant No.550171001)support provided by the Deutsche Forschungsgemeinschaft(DFG,German Research Founda-tion)-TRR 288/2-422213477(project B06).
文摘Interlayer interactions in bilayer or multilayer electron systems have been studied extensively,and many exotic physical phenomena have been revealed.However,systematic investigations of the impact of interlayer interactions on magnonic physics are very few.Here,we use a van derWaals(vdW)honeycomb heterostructure as a platform to investigate the modulation of magnon properties in honeycomb AA-and AB-stacking heterostructures with ferromagnetic and antiferromagnetic interlayer interactions,including topological phases and thermal Hall conductivity.Our results reveal that interlayer interactions play a crucial role in modulating the magnonic topology and Hall transport properties of magnetic heterostructures,with potential for experimental realization.
文摘Background:Cardiovascular disease remains the leading cause of mortality across the European region.Despite marked regional variations,cross-national differences in underlying risk factors have received comparatively little attention.Objective:To use European Social Survey,a unique cross-European dataset,to examine regional patterns in prevalence and lifestyle risks.Methods:This study employs clustering analysis and nested logistic modelling.Counterfactual analysis was conducted to illustrate how lifestyle modifications could reduce risk.Results:The prevalence of heart problems was highest in Latvia(25.6%,95%CI:23.0 to 28.2),Lithuania(17.6%,95%CI:15.5 to 19.7),and Bulgaria(14.9%,95%CI:13.4 to 19.4).Regionally,heart problems were higher in Northern and Eastern Europe(15%and 11.9%)than Western and Southern Europe(10.8%and 9.5%).Among the risk factors,modelling emphasised the importance of modifiable factors including education,body mass index and physical activity.Conclusion:The results underline that cardiovascular disease is influenced by interrelated socioeconomic,environmental and lifestyle determinants.Public policy interventions could be targeted at those countries where greatest reductions are obtainable and concentrate on interventions on those lifestyle traits identified.The study utilised a social science dataset,thereby illustrating how multidisciplinary resources can benefit epidemiological research.
文摘In ethnopharmacology, and especially in traditional Chinese medicine, medicinal plants have been used for thousands of years. Similarly, agricultural plants have been used throughout the history of mankind. The recent development of the genetic engineering of plants to produce plants with desirable features adds a new and growing dimension to humanity’s usage of plants. The biotechnology of plants has come of age and a plethora of bioengineering applications in this context have been delineated during the past few decades. Callus cultures and suspension cell cultures offer a wide range of usages in pharmacology and pharmacy (including Chinese medicine), as well as in agriculture and horticulture. This review provides a timely overview of the advancements that have been made with callus cultures in these scientific fields. Genetically modified callus cultures by gene technological techniques can be used for the synthesis of bioactive secondary metabolites and for the generation of plants with improved resistance against salt, draft, diseases, and pests. Although the full potential of callus plant culture technology has not yet been exploited, the time has come to develop and market more callus culture-based products.
基金Supported by The University of Mainz Project Grant
文摘AIM： To analyze the relevance of the microRNA miR-196a for colorectal oncogenesis.METHODS： The impact of miR-196a on the restriction targets HoxA7, HoxBS, HoxC8 and HoxD8 was analyzed by reverse transcription polymerase chain reaction（RT-PCR） after transient transfection of SW480 cancer cells. The miR-196a transcription profile in colorectalcancer samples, mucosa samples and diverse cancercell lines was quantified by RT-PCR. Transiently miR-196a-transfected colorectal cancer cells were used for diverse functional assays in vitro and for a xenograft lung metastasis model in vivo.RESULTS： HoxA7, HoxB8, HoxC8 and HoxD8 wererestricted by miR-196a in a dose-dependent andgene-specific manner. High levels of miR-196aactivated the AKT signaling pathway as indicated byincreased phosphorylation of AKT. In addition, highlevels of miR-196a promoted cancer cell detachment,migration, invasion and chemosensitivity towardsplatin derivatives but did not impact on proliferationor apoptosis. Furthermore, miR-196a increased thedevelopment of lung metastases in mice after tail veininjection.
文摘The completely assembled human genome has made it possible for modern medicine to step into an era rich in genetic information and high-throughput genomic analysis. These novel and readily available genetic resources and analytical tools may be the key to unravel the molecular basis of hepatocellular carcinoma (HCC). Moreover, since an efficient treatment for this disease is lacking, further understanding of the genetic background of HCC will be crucial in order to develop new therapies aimed at selected targets. We report on the current status and recent developments in HCC genetics. Special emphasis is given to the genetics and regulation of major signalling pathways involved in HCC such as p53, Wnt- signalling, TGFβ, Ras, and Rb pathways. Furthermore, we describe the influence of chromosomal aberrations as well as of DNA methylation. Finally, we report on the rapidly developing field of genomic expression profiling in HCC, mainly by microarray analysis.
文摘Carcinomas of the stomach and gastroesophageal junction are among the five top leading cancer types worldwide. In spite of radical surgical R0 resections being the basis of cure of gastric cancer, surgery alone provides long-term survival in only 30% of patients with advanced International Union Against Cancer （UICC） stages in Western countries because of the high risk of recurrence and metachronous metastases. However, recent large phase-Ⅲ studies improved the diagnostic and therapeutic options in gastric cancers, indicating a more multidisciplinary management of the disease. Multimodal strategies combining different neoadjuvant and/or adjuvant protocols have clearly improved the gastric cancer prognosis when combined with surgery with curative intention. In particular, the perioperative （neoadjuvant, adjuvant） chemotherapy is now a well-established new standard of care for advanced tumors. Adjuvant therapy alone should be carefully discussed after surgical resection, mainly in individual patients with large lymph node positive tumors when neoadjuvant therapy could not be done. The palliative treatment options have also been remarkably improved with new chemotherapeutic agents and will further be enhanced with targeted therapies such as different monoclonal antibodies. This article reviews the most relevant literature on the multidisciplinary management of gastric and gastroesophageal cancer, and discusses future strategies toimprove Iocoregional failures.
文摘AIM:To gain mechanistic insights into the role played by epidermal growth factor receptor (EGFR) in the regulation of vascular endothelial growth factors (VEGFs) in colorectal cancer (CRC). METHODS:The impact of high-level expression of the growth factor receptors EGFR and VEGF receptor (VEGFR)3 and the VEGFR3 ligands VEGF-C and VEGF-D on disease progression and prognosis in human CRC was investigated in 108 patients using immunohistochemistry. Furthermore, the expression of the lymphangiogenic factors in response to the modulation of EGFR signalling by the EGFR-targeted monoclonal antibody cetuximab was investigated at the mRNA and protein level in human SW480 and SW620 CRC cell lines and a mouse xenograft model. RESULTS: Human CRC specimens and cell lines displayed EGFR, VEGF-C and VEGF-D expression with varying intensities. VEGF-C expression was associated with histological grade. Strong expression of VEGF-D was significantly associated with lymph node metastases and linked to a trend for decreased survival in lymph node-positive patients. EGFR blockade with cetuximab resulted in a significant decrease of VEGF-D expression in vitro and in vivo. CONCLUSION:In conclusion, the expression of VEGF-D in colorectal tumours is significantly associated with lymphatic involvement in CRC patients and such expression might be blocked effectively by cetuximab.
文摘To review the implication of CXCR4 for gastrointestinal cancer, a ＂Pubmed＂ analysis was performed in order to evaluate the relevance of CXCR4 and its ligands for gastrointestinal cancers. Search terms applied were ＂cancer, malignoma, esophageal, gastric, colon, colorectal, hepatic, pancreatic, CXCR4, SDF- 1α, and SDF-1β＂. CXCR4 expression correlated with dissemination of diverse gastrointestinal malignomas. The CXCR4 ligand SDF-1α might act as ＂chemorepellent＂ while SDF-1β might act as ＂chemorepellent＂ for CTLs, inducing tumor rejection. The paracrine expression of SDF-1α was furthermore closely associated with neoangiogenesis. CXCR4 and its ligands influence the dissemination, immune rejection, and neoangiogenesis of human gastrointestinal cancers. Inhibition of CXCR4 might be an interesting therapeutic option.
文摘AIM： To define the （co-）expression pattern of target receptor-tyrosine-kinases （RTK） in human gastric adenocarcinoma. METHODS： The （co-）expression pattern of VEGFR1-3, PDGFR（α/β and EGFR1 was analyzed by RT-PCR in 51 human gastric adenocarcinomas. In addition, IHC staining was applied for confirmation of expression and analysis of RTK localisation. RESULTS： The majority of samples revealed a VEGFR1 （98%）, VEGFR2 （80%）, VEGFR3 （67%）, PDGFRα （82%） and PDGFRβ （82%） expression, whereas only 62% exhibited an EGFR1 expression. 78% of cancers expressed at least four out of six RTKs. While VEGFR1-3 and PDGFRα revealed a predominantly cytoplasmatic staining in tumor cells, accompanied by an additional nuclear staining for VEGFR3, EGFR1 was almost exclusively detected on the membrane of tumor cells. PDGFRβ was restricted to stromal pericytes, which also depicted a PDGFRα expression. CONCLUSION： Our results reveal a high rate ofreceptor-tyrosine-kinases coexpression in gastric adenocarcinoma and might therefore encourage an application of multiple-target RTK-inhibitors within a combination therapy.
文摘AIM: To evaluate and confirm the low incidence of hepatocellular carcinoma (HCC) in patients with autoimmune hepatitis (AIH). At present only very few cases of HCC in patients with AIH and definite exclusion of chronic viral hepatitis have been published, suggesting that HCC due to AIH is rare. METHODS: In order to further investigate the incidence of HCC in patients with AIH, we reviewed our large cohort of 278 patients with AIH. RESULTS: Eighty-nine patients (32%) were diagnosed with liver cirrhosis, a preneoplastic condition for HCC. We studied a total of 431 patient years of cirrhosis in these patients, an average 4.8 years per patient. During this period none of the patients of our own study cohort developed HCC. However, three patients with HCC due to AIH associated liver cirrhosis were referred to our department for further treatment of HCC. In all three patients chronic viral hepatitis was excluded. CONCLUSION: We conclude that HCC may under rare circumstances develop due to chronic AIH dependent liver cirrhosis. Compared to other causes of liver cirrhosis such as chronic viral hepatitis, alcohol, or hemochromatosis, the incidence of HCC is significantly lower. Pathophysiological differences between AIH and chronic viral hepatitis responsible for differences in the incidence of HCC are yet to be further characterized and may lead to new therapeutic concepts in prevention and treatment of liver cancer.
文摘The aim of this study was to investigate the physiological foramen diameter, shape and distance between physiological and anatomical apex of maxillary and mandibular first and second molars. Accurate knowledge of the physiological foramina morphology; thus, inherent mechanical shaping technical hindrances, is decisive when taking the corresponding root canal final preparation decision. The morphological dimensions of a total of 1 727 physiological foramina were investigated by means of micro-computed tomography. Mean narrow and wide （to a high number, oval） diameters of the physiological foramen were 0.24, 0.22 and 0.33 mm and 0.33, 0.31 and 0.42 mm in mesiobuccal （MB）, distobuccal （DB） and palatal （P） roots in maxillary first molars; 0.24, 0.22 and 0.33 mm and 0.41, 0.33 and 0.44 in MB, DB, and P roots in maxillary second molars. Mandibular first molars showed mean narrow and wide diameters of 0.24 and 0.30 mm and of 0.39 and 0.46 mm in mesial （M） and distal （D） roots; second mandibular molars showed 0.25 and 0.31 mm and 0.47 mm in M and D roots. The mean distance between the physiological foramina and anatomical apex was 0.82, 0.81 and 1.02 mm and 0.54, 0.43 and 0.63 mm in MB, DB and P roots of the maxillary first and second molars, respectively. A mean distance of 0.95 mm （M） and 1.05 mm （D） in the first and 0.78 mm （M） and 0.81 mm （D） in the second mandibular molars was observed. Based on the results obtained, assumable recommendations for final preparation size of the physiological foramen were calculated. However, when taking into consideration, the resulting standard deviations of marginal errors must be cautiously considered when taking a final decision in clinical endodontic treatment.
基金supported by the Deutsche Forschungsgemeinshaft (to CJ)。
文摘Schwann cells,the myelinating glia of the peripheral nervous system,wrap axons multiple times to build their myelin sheath.Myelin is of paramount importance for axonal integrity and fast axon potential propagation.However,myelin is lacking or dysfunctional in several neuropathies including demyelinating and dysmyelinating Charcot-M arie-To oth disease.Charcot-Marie-To oth disease represents the most prevalent inherited neuropathy in humans and is classified either as axonal,demyelinating or dysmyelinating,or as intermediate.The demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease constitute the majority of the disease cases and are most frequently due to mutations in the three following myelin genes:peripheral myelin protein 22,myelin protein ze ro and gap junction beta 1(coding for Connexin 32) causing Charcot-M arie-Tooth disease type 1A,Charcot-Marie-Tooth disease type 1B,and X-linked Charcot-M arie-Tooth disease type 1,respectively.The resulting perturbation of myelin structure and function leads to axonal demyelination or dysmyelination and causes severe disabilities in affected patients.No treatment to cure or slow down the disease progression is currently available on the market,howeve r,scientific discoveries led to a better understanding of the pathomechanisms of the disease and to potential treatment strategies.In this review,we describe the features and molecular mechanisms of the three main demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease,the rodent models used in research,and the emerging therapeutic approaches to cure or counteract the progression of the disease.
文摘Artemisinin,a constituent of Artemisia annua L.,is a well-known antimalarial drug.Artemisinin-type drugs also inhibit cancer growth in vitro and in vivo.Herbal extracts of A.annua inhibit the growth of cancer cell lines.Here,we report on the use of capsules containing powder of Herba Artemisiae annuae to treat pet sarcoma.The surgical tumor removal as standard treatment was supplemented by adjuvant therapy with A.annua.One cat and one dog with fibrosarcoma survived 40 and 37 months,respectively,without tumor relapse.Two other dogs suffering from fibrosarcoma and hemangioendothelial sarcoma also showed complete remission and are still alive after 39 and 26 months,respectively.A.annua was well tolerated without noticeable side effects.These four cases indicate that A.annua may be a promising herbal drug for cancer therapy.
文摘AIM： To study, whether the association of Schatzki rings with other esophageal disorders support one of the theories about its etiology. METHODS： From 1987 until 2007, all patients with newly diagnosed symptomatic Schatzki rings （SRs） were prospectively registered and followed. All of them underwent structured interviews with regards to clinical symptoms, as well as endoscopic and/or radiographic examinations. Endoscopic and radiographic studies determined the presence of an SR and additional morp- hological abnormalities. RESULTS： One hundred and sixty-seven patients （125 male, 42 female） with a mean age of 57.1±14.6 years were studied. All patients complained of intermittent dysphagia for solid food and 113 （79.6%） patients had a history of food impaction. Patients experienced symptoms for a mean of 4.7± 5.2 years before diagnosis. Only in 23.4% of the 64 patients who had endoscopic and/or radiological examinations before their first presentation to our clinic, was the SR previously diagnosed. At presentation, the mean ring diameter was 13.9 4- 4.97 mm. One hundred and sixty-two （97%） patients showed a sliding hiatal hernia. Erosive reflux esophagitis was found in 47 （28.1%） patients. Twenty-six （15.6%） of 167 patients showed single or multiple esophageal webs; five （3.0%） patients exhibited eosinophilic esophagitis; and four （2.4%） had esophageal diverticula. Four （7%） of 57 patients undergoing esophageal manometry had non- specific esophageal motility disorders. CONCLUSION： Schatzki rings are frequently associated with additional esophageal disorders, which support the assumption of a multifactorial etiology. Despite typical symptoms, SRs might be overlooked.
基金supported by the German Research Foundation (DFG):SFB-TR-128 (to SG,MM),MU 4354/1-1(to MM)the Boehringer Ingelheim Fonds BIF-03 (to SG,MM)。
文摘Parkinson's disease(PD) is one of the most common neurodegenerative diseases,affecting individuals especially over 60 years of age.In the next three decades,more than 12 million people will suffer from PD worldwide(Rocca,2018).The characteristic symptoms of PD begin as a movement disorder including bradykinesia,resting tremor,rigidity,and postural instability.
