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Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion

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World Journal of Gastroenterology 2017年第48期23卷 8443-8451页

作者： Yuri L Boteon Richard Laing Hynek Mergental Gary M Reynolds darius f mirza Simon C Afford Ricky H Bhogal The Liver Unit University Hospitals of BirminghamMindelsohn Way The Centre for Liver Research Institute for Biomedical ResearchUniversity of Birmingham

Ischaemia-reperfusion injury(IRI) is the leading cause of injury seen in the liver following transplantation. IRI also causes injury following liver surgery and haemodynamic shock. The first cells within the liver to be injured by IRI are the liver sinusoidal endothelial cells(LSEC). Recent evidence suggests that LSEC coordinate and regulates the livers response to a variety of injuries. It is becoming increasingly apparent that the cyto-protective cellular process of autophagy is a key regulator of IRI. In particular LSEC autophagy may be an essential gatekeeper to the development of IRI. The recent availability of liver perfusion devices has allowed for the therapeutic targeting of autophagy to reduce IRI. In particular normothermic machine liver perfusion(NMP-L) allow the delivery of pharmacological agents to donor livers whilst maintaining physiological temperature and hepatic flow rates. In this review we summarise the current understanding of endothelial autophagy and how this may be manipulated during NMP-L to reduce liver IRI.

关键词： Autophagy Liver transplant Ischaemiareperfusion injury Normothermic machine liver perfusion

Late post liver transplant protein losing enteropathy: Rare complication of incisional hernia

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World Journal of Gastroenterology 2013年第27期19卷 4409-4412页

作者： Jonathan D Evans M Thamara PR Perera CY Pal James Neuberger darius f mirza The Liver Unit The Queen Elizabeth Hospital

Development of oedema and hypoproteinaemia in a liver transplant recipient may be the first signs of graft dysfunction and should prompt a full assessment. We report the novel case of a patient who, years after liver transplantation developed a functional blind loop in an incisional hernia, which manifested as oedema and hypoproteinaemia secondary to protein losing enteropathy. After numerous investigations, the diagnosis was made by flurodeoxyglucose positron emmision tomography (fDG-PET) imaging. Surgical repair of the incisional hernia was followed several months later by resolution of the protein loss, and confirmed at a post operative fDG-PET scan at one year.

关键词： Protein losing enteropathies Bacterial overgrowth Hypoproteinaemia Incarcerated hernia Liver transplantation.

Hepatic vein reconstruction during hepatectomy:A feasible and underused technique

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 421-427页

作者： Manish Ahuja Kunal Joshi Chris Coldham Paulo Muiesan Bobby Dasari Manuel Abradelo Ravi Marudanayagam darius mirza John Isaac David Bartlett Nikolaos A Chatzizacharias Robert P Sutcliffe Keith J Roberts Department of HPB and Liver Transplant Surgery University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Immunology and Immunotherapy University of BirminghamBirminghamUK

Complete surgical resection(R0)of liver tumors,primary or metastatic,remains the main objective in management of primary and metastatic liver tumors[1].Tumors invading to the proximity of the hepatic venous outflow pose a peculiar challenge to achieve R0 resections,because this location may render a tumor *** median survival of patients with liver tumor without surgery is less than 12 months[2].Even with surgery,post-hepatectomy liver failure and subsequently increased mortality are the main problems associated with complex resection[3].Moreover,when the vein is affected,vein resection and subsequent reconstruction are *** resection is a standard practice in liver resection and transplantation[4],for example,hepatic vein reconstruction during a living-donor liver transplant,porto-mesenteric axis reconstruction during resection of advanced pancreatic cancer and caval reconstruction during resection of retroperitoneal ***,novel techniques like total hepatic vascular exclusion(HVE)[5],veno-venous bypass[6]and ex vivo hepatic resection[7,8]have facilitated curative resections of tumors close to one or more major hepatic veins.

关键词： hepatectomy surgery mortality

Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants

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Hepatobiliary & Pancreatic Diseases International 2006年第1期5卷 154-156页

作者： Vincent Lai David Mutimer darius mirza Department of Liver Surgery

BACKGROUND: The recurrence of chronic hepatitis B after liver transplantation results in increased risk for graft failure and death of patients. Lamivudine has been shown to be effective in the treatment of chronic hepatitis B, but resistance to this agent is common after prolonged administration. METHODS: One patient with chronic hepatitis B virus (HBV) infection developed resistance to lamivudine after 15 months of treatment. The resistance was confirmed by mutation in the HBV DNA polymerase gene. The patient was treated subsequently with adefovir dipivoxil for 7 months. RESULT: HBV DNA and HBsAg were tested negative, but HBeAb and HBsAb were positive. CONCLUSION: This study provides an evidence that adefovir dipivoxil can be effective in the treatment of lamivudine-resistant HBV mutants.

关键词： adefovir dipivoxil hepatitis B virus liver transplantation lamivudine

Venous resection at pancreaticoduodenectomy can be safely performed in the presence of jaundice

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Hepatobiliary & Pancreatic Diseases International 2020年第5期19卷 488-491页

作者： Rupaly Pande James Hodson Ravi Marudanayagam darius mirza John Isaac Keith J Roberts HPB Surgery University Hospitals Birmingham NHS Foundation TrustBirmingham B152THUK Institute of Translational Medicine University Hospitals Birmingham NHS Foundation TrustBirmingham B152THUK Institute of Immunology and Immunotherapy University of BirminghamBirmingham B152THUK

Venous resection at pancreaticoduodenectomy(PD)has established itself as a viable treatment for borderline resectable cancer,with equivalent survival to those patients undergoing PD for cancer without venous resection[1].Thus surgery for these patients is clearly desirable,when possible,compared to palliative ***,there is concern and debate about the safety of venous resection at PD[2].There is a need to improve patient pathways,outcome and experience[3].To this end,in patients who present with jaundice,it is clear that surgery without preoperative biliary drainage(PBD)reduces complications[4].In 2015,our team introduced a‘fast track’program to routinely perform PD in the presence of jaundice[5].This change of practice has become routine,with most patients now undergoing surgery without *** is,however,unclear whether portal vein(PV)resection+PD is safe in the setting of *** aim of this study,therefore,was to compare outcomes and complications between patients with or without jaundice undergoing PD with associated resection of the superior mesenteric vein(SMV)and/or PV.

关键词： jaundice resection routine

Ventilation after pancreaticoduodenectomy increases perioperative mortality: Identification of risk factors and their relevance in Germany that do not apply in England

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Hepatobiliary & Pancreatic Diseases International 2019年第4期18卷 379-388页

作者： Rieke-Sophie Homeyer Keith JRoberts Robert P Sutcliffe Alexander Kaltenborn darius mirza Zhi Qu Jurgen Klempnauer Harald Schrem Core facility Quality Management Transplantation Integrated Research and Treatment Center Transplantation(IFB-Tx)Hannover Medical SchoolCarl-Neuberg-Str.130625 HannoverGermany General Visceral and Transplant SurgeryHannover Medical SchoolCarl-Neuberg-Str.130625 HannoverGermany Department of HPB Surgery Queen Elizabeth Hospital BirminghamMindelsohn Way EdgbastonBirmingham B15 2GWUnited Kingdom Department of General Visceral and Transplant SurgeryMedical University GrazAuenbrugger Platz 58036 GrazAustria

Background:Pre-operative risk factors for post-operative ventilation and their influence on survival after pancreaticoduodenectomy for malignancy are ***:Totally 391 patients operated in Hannover,Germany were investigated with multivariable logistic regression and Cox regression modeling to identify independent risk factors for post-operative ventilation≥6 h,patient survival and 90-day *** 84 patients operated in Birmingham,United Kingdom were analyzed to assess the external relevance of ***:Longer operations,history of thrombosis,intra-operative blood transfusion,lower estimated glomerular filtration rates(eGfR)and higher values of the age at operation divided by the Horovitz Quotient independently increased the risk of post-operative ventilation≥6 h in German patients(n=108;27.6%)(Pfusion and lower pre-operative eGfR levels increased the risk of early death in German patients significantly and independently of established prognostic factors.A history of thrombosis and lower eGfR levels were also independent significant risk factors for 90-day mortality in German patients but not in English *** of the English patients received post-operative *** more German patients were>75 years,had a history of thrombosis,received blood transfusions,and had significantly worse lung function ***4 tumors were detected in 18 German patients(4.6%),but not in the English ***:Identified risk factors for post-operative ventilation are clinically relevant in Germany but not in England and may be used to lower mortality *** German and the English cohorts displayed significant differences in the approach to patient selection and early post-operative extubation.

关键词： Pancreatic cancer Cholangiocellular carcinoma Periampullary carcinoma Comorbidity Outcome

Low-loss optical waveguides made with a high-loss material

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Light(Science & Applications) 2021年第1期10卷 12-18页

作者： darius Urbonas Rainer f.Mahrt Thilo Stoferle IBM Research Europe—Zurich Saumerstrasse 48803 RuschlikonSwitzerland

for guiding light on a chip,it has been pivotal to use materials and process flows that allow low absorption and *** on subwavelength gratings,here,we show that it is possible to create broadband,multimode waveguides with very low propagation losses despite using a strongly absorbing *** perform rigorous coupled-wave analysis and finite-difference time-domain simulations of integrated waveguides that consist of pairs of integrated high-index-contrast *** showcase this concept,we demonstrate guiding of visible light in the wavelength range of 550-650 nm with losses down to 6dB/cm using silicon gratings that have a material absorption of 13,000 dB/cm at this wavelength and are fabricated with standard silicon photonics *** approach allows us to overcome traditional limits of the various established photonics technology platforms with respect to their suitable spectral range and,furthermore,to mitigate situations where absorbing materials,such as highly doped semiconductors,cannot be avoided because of the need for electrical driving,for example,for amplifiers,lasers and modulators.

关键词： waveguides absorbing absorption

A modified Johnson-Cook constitutive relationship for a rare-earth containing magnesium alloy

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Journal of Rare Earths 2013年第12期31卷 1202-1207页

作者： f.A.mirza 陈道伦李德江曾小勤 Department of Mechanical and Industrial Engineering Ryerson University The State Key Laboratory of Metal Matrix Composites School of Materials Science and EngineeringShanghai Jiao Tong University

Lightweight magnesium alloy has recently attracted a considerable interest in the automotive and aerospace industries to improve fuel efficiency and reduce CO2 emissions via the weight reduction of ***-earth（RE） element addition can remarkably improve the mechanical properties of magnesium alloys through weakening crystallographic textures associated with the strong mechanical anisotropy and tension-compression yield *** the addition of RE elements sheds some light on the alteration in the mechanical anisotropy,available information on the constitutive relationships used to describe the flow behavior of RE-containing magnesium alloys is *** establish such a constitutive relationship,uniaxial compressive deformation tests were first conducted on an extruded Mg-10Gd-3Y-0.5Zr（GW103K） magnesium alloy at the strain rates ranging from 1×10–1 to 1×10–4s–1 at room temperature.A modified Johnson-Cook constitutive equation based on a recent strain hardening equation was proposed to predict the flow stresses of GW103K *** between the predicted and experimental results showed that the modified Johnson-Cook constitutive equation was able to predict the flow stresses of the RE-containing magnesium alloy fairly accurately with a standard deviation of about 1.8%.

关键词： magnesium alloy rare-earth element compression constitutive equation

Dock-able linear and homodetic di, tri, tetra and pentapeptide library from canonical amino acids: SARS-CoV-2 Mpro as a case study

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Journal of Pharmaceutical Analysis 2023年第5期13卷 523-534页

作者： Sarfraz Ahmad Muhammad Usman mirza John f.Trant Department of Chemistry and Biochemistry University of WindsorWindsor N9B 3P4OntarioCanada Binary Star Research Services LaSalle N9J 3X8OntarioCanada

Peptide-based therapeutics are increasingly pushing to the forefront of biomedicine with their promise of high specificity and low *** noncanonical residues can always be used,employing only the natural 20 residues restricts the chemical space to a finite dimension allowing for comprehensive in silico *** this goal,the dataset comprising all possible di-,tri-,and tetra-peptide combinations of the canonical residues has been previously ***,with increasing computational power,the comprehensive set of pentapeptides is now also feasible for screening as the comprehensive set of cyclic peptides comprising four or five ***,we provide both the complete and prefiltered libraries of all di-,tri-,tetra-,and penta-peptide sequences from 20 canonical amino acids and their homodetic(N-to-C-terminal)cyclic *** fASTA,simplified molecular-input line-entry system(SMILES),and structure-data file(SDf)-three dimension(3D)libraries can be readily used for screening against protein *** also provide a simple method and tool for conducting identity-based *** to this dataset will accelerate small peptide screening workflows and encourage their use in drug discovery *** a case study,the developed library was screened against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)main protease to identify potential small peptide inhibitors.

关键词： Dipeptides Tripeptides Tetrapeptides Pentapeptides N-to-C-terminal cyclic peptides Peptide library