Background: Gangrenous cystitis is an extremely rare condition with very few cases reported in li... more Background: Gangrenous cystitis is an extremely rare condition with very few cases reported in literature. Diagnosis is often delayed due to the nonspecifi c symptoms. A multidisciplinary team approach and surgical debridement is usually required for management. Case presentation: This case reports a 27 year old female who developed gangrenous cystitis postpartum. She was managed with partial cystectomy and primary closure of urinary bladder. Conclusion: Gangrenous cystitis is a condition with high morbidity and mortality. A high index of suspicion is necessary for diagnosis.
Journal of College of Medical Sciences-nepal, Dec 28, 2015
INTRODUCTION Injury to Anterior Cruciate Ligament (ACL) reconstruction has increased because of i... more INTRODUCTION Injury to Anterior Cruciate Ligament (ACL) reconstruction has increased because of increased interest in sports. Rupture of ACL may lead to instability, pain, swelling, mechanical dysfunction and an increased risk of meniscal injury and degenerative changes. 1-5 Non operative treatment may lead to suboptimal knee function and to joint detoriation. 4,6,7 For this reason many procedures have been developed to restore stability and allow patient to have more active life. The reconstruction of ACL with central third of patellar tendon with proximal and distal bone blocks has been shown to produce dependable results. 2,8 The fixation of these grafts is most commonly performed with metal or bioabsorbable interference screw. This procedure is well
Cases of extra uterine translocation of intrauterine contraceptive device (IUCD) to adjacent stru... more Cases of extra uterine translocation of intrauterine contraceptive device (IUCD) to adjacent structures like peritoneal cavity, urinary bladder & sigmoid colon have been reported. Here is a case of translocation of IUCD into the caecum presenting as appendicitis. Appendicitis resulting from IUCD translocation is very rare. As per our knowledge only 19 cases have been reported earlier.
Introduction: There are ways to operate for herniated cervical disc starting from simple discecto... more Introduction: There are ways to operate for herniated cervical disc starting from simple discectomy to artificial disc replacement. Methods and Materials: This is a prospective study of anterior cervical discectomy and fusion with polyetheretherketone (PEEK) age device conducted from January 2016 to September 2019. Age, sex ratio, level of disc prolapses, symptoms, complications of surgery and the outcome was assessed. Neurological assessment was done pre and postoperatively as defined by Odom's criteria and Ranawat et al grading system. Check x-ray was done at three and six months. Results: The total number of cases was 82, predominantly males (62%). Disc prolapse due to degenerative disease was the most common case (68%). C5-6 was the most often disc prolapse level (40%), followed by C6-7 level (38%) and multiple level disc prolapse in 12%. Applying Ranawat grading system of neurological deficit; at presentation, majority were in Grade II (54%), followed by Grade IIIA (19%). Postoperatively there was reduction in weakness from 54% to 16% in Grade II and from 19% to 8% for Grade IIIA. Majority had excellent and good outcome based on Odom's criteria. The continuity of the graft and the adjacent spinal curvature was also assessed and there was more than 96% fusion rate. Conclusion: Use of local autograft with a PEEK cage has a benefit of working within the same operative window as the ACDF, thus reducing the infection, bleeding, and pain risks that may be encountered with a second incision. It is very safe to use in single level or multilevel cervical disc prolapse and also saves additional time of harvesting graft from the donor site.
Journal of International Medical Research, Apr 1, 2022
ObjectiveTo investigate the effects of piperlongumine (PL) and vitamin C (VC) on signal transduce... more ObjectiveTo investigate the effects of piperlongumine (PL) and vitamin C (VC) on signal transducer and activator of transcription 3 (STAT3) signalling in gastric cancer cell lines.MethodsIn vivo tumour xenograft anticancer assays were undertaken to confirm the anticancer activity of PL. Cell viability, flow cytometry and Western blot assays were undertaken to evaluate the anticancer effects of PL, VC and combinations of PL and VC in AGS and KATO III cells.ResultsBoth PL and VC induced apoptosis and inhibited cell proliferation in AGS and KATO III cells. These effects were dependent on reactive oxygen species (ROS). PL effectively suppressed STAT3 activation while VC caused abnormal activation of STAT3. The combination of PL and VC exhibited a stronger apoptotic effect compared with either agent alone. PL reversed the abnormal activation of STAT3 by VC, which could be a key to their synergistic effect.ConclusionsPL combined with VC exhibited a stronger anticancer effect by regulating the ROS–STAT3 pathway, suggesting that this combination might be a potential adjuvant therapy for gastric cancer.
The long-noncoding RNAs (lncRNAs) have been identified as key players in diverse cellular process... more The long-noncoding RNAs (lncRNAs) have been identified as key players in diverse cellular processes in non-small cell lung cancer (NSCLC). However, the understanding of biological functions and detailed mechanisms of lncRNAs is still limited. Herein, the lncRNA cancer susceptibility candidate 9 (CASC9) on NSCLC progression is investigated. Materials and Methods: Expressions of CASC9, HuR and cell division cycle 6 (CDC6) in NSCLC tissues were detected with quantitative real-time polymerase chain reaction (qRT-PCR). The cell counting kit-8, transwell assays, and flow cytometry were used to examine cell proliferation, migration, and the cell cycle. Tumor growth in vivo was evaluated by xenograft tumor experiments and immunohistochemistry. RNA-binding protein immunoprecipitation (RIP) was used to identify the interaction between HuR and CDC6, and CASC9 and HuR. Results: CASC9, CDC6 and HuR expression were found significantly upregulated in NSCLC tissues, which predicted poorer 5-year overall survival in NSCLC patients. Inhibition of CASC9 significantly reduced the malignancy of NSCLC cells, such as proliferation, migration and cell cycle. In vivo experiments further demonstrated that CASC9 knockdown reduced the tumor growth and the Ki-67 expression. Moreover, CASC9 knockdown inhibited the expression of CDC6 which was detected overexpressed in NSCLC tumor tissues. Then, up-regulation of CDC6 could partly reverse the negative effects of CASC9 on cell proliferation, migration and cell cycle. RIP assay and rescue experiment showed that CASC9 regulated CDC via binding to HuR. Conclusion: Our results indicate that CASC9 conferred an aggressive phenotype in NSCLC and might be a pivotal target for this disease.
C yr61 is a 42 kDa secreted protein from CCN-family, containing four different conserved molecula... more C yr61 is a 42 kDa secreted protein from CCN-family, containing four different conserved molecular domains. Overproduction of Cyr61/CCN1 plays a critical role in the development and progression of pancreatic cancer, through the induction of EMT and stemness. Pancreatic cancer stem cells (PCSC) are rare tumour cells characterized by their ability to self-renew, and are responsible for tumour recurrence accompanied by resistance to current therapies. Shh pathway is highly activated in pancreatic CSCs and plays important role in maintaining stemness by regulating the expression of stemness genes. Cyr61 expression has been found to be exorbitantly higher in cancer stem/tumour initiating Panc-1-side-population (SP) cells. Cyr61/CCN1 silencing in pancreatic CSCs results in reduced aggressive behaviour, reversing of the EMT, blocking of the expression of stem-cell-like traits and inhibition in migration. In contrast, addition of Cyr61 protein in culture medium augments EMT and stemness features in relatively less aggressive BxPC3 pancreatic cancer cells. The objective of this study is to investigate the role of CCN1 & Shh pathway in pancreatic cancer and to examine the molecular mechanisms by which CCN1 acts as a regulator for Shh pathway. Another objective of this study is to examine the molecular mechanisms by which resveratrol inhibits stem cell characteristics of pancreatic CSCs derived from human primary tumours and KrasG12D transgenic mice. Hence, this study aims to identify the role of CCN1 in pancreatic cancer and the possibility of resveratrol to be used as a therapeutic agent.
Abdominal complications after placement of ventriculoperitoneal (VP) shunt are commonly reported ... more Abdominal complications after placement of ventriculoperitoneal (VP) shunt are commonly reported but asymptomatic bowel perforation with enterocutaneous fistula (ECF) is rare. This case describes a young male patient who underwent VP shunt for hydrocephalus 10 years ago. He presented with ECF due to the non-functioning abdominal end of the shunt. Patient was managed with laparotomy with fistulectomy with bowel resection and anastomosis. ECF is a rare complication of VP shunt.
Spontaneous regression of cerebral arteriovenous malformation is rare and less than hundred cases... more Spontaneous regression of cerebral arteriovenous malformation is rare and less than hundred cases have been reported in literature. The authors report a case of 64 year/male who was diagnosed with cerebral arteriovenous malformation which was found to undergo spontaneous regression on repeat imaging. Spontaneous regression of a cerebral arteriovenous malformation is a rare phenomenon.
Herein, we characterize the cellular uptake of a DNA structure generated by rolling circle DNA am... more Herein, we characterize the cellular uptake of a DNA structure generated by rolling circle DNA amplification. The structure, termed nanoflower, was fluorescently labeled by incorporation of ATTO488-dUTP allowing the intracellular localization to be followed. The nanoflower had a hydrodynamic diameter of approximately 300 nanometer and was nontoxic for all mammalian cell lines tested. It was internalized specifically by mammalian macrophages by phagocytosis within a few hours resulting in specific compartmentalization in phagolysosomes. Maximum uptake was observed after eight hours and the nanoflower remained stable in the phagolysosomes with a half-life of 12 h. Interestingly, the nanoflower co-localized with both Mycobacterium tuberculosis and Leishmania infantum within infected macrophages although these pathogens escape lysosomal degradation by affecting the phagocytotic pathway in very different manners. These results suggest an intriguing and overlooked potential application of DNA structures in targeted treatment of infectious diseases such as tuberculosis and leishmaniasis that are caused by pathogens that escape the human immune system by modifying macrophage biology.
Topoisomerases maintain topological homeostasis of bacterial chromosomes by catalysing changes in... more Topoisomerases maintain topological homeostasis of bacterial chromosomes by catalysing changes in DNA linking number. The resolution of RNA entanglements occurring in the cell would also require catalytic action of topoisomerases. We describe RNA topoisomerase and hydrolysis activities in DNA topoisomerase I (topo I) from mycobacteria. The interaction of topo I with mRNA, tRNA and rRNA suggested its role in some aspect of RNA metabolism; the enzyme participates in rRNA maturation via its RNA hydrolysis activity. Accumulation of rRNA precursors in a topo I knockdown strain and the rescue of rRNA processing deficiency in RNaseE knockdown cells by topo I expression indicated the enzyme's backup support to RNases involved in rRNA processing. We demonstrate that the active-site tyrosine of the enzyme mediates catalytic reactions with both DNA/RNA substrates, and RNA topoisomerase activity can follow two reaction paths in contrast to its DNA topoisomerase activity. Mutation in the canonical proton relay pathway impacts DNA topoisomerase activity whilst retaining activity on RNA substrates. The mycobacterial topo I thus exemplifies the resourcefulness and parsimony of biological catalysis in harnessing the limited chemical repertoire at its disposal to find common solutions to mechanistically related challenges of phosphodiester breakage/exchange reactions in DNA and RNA that are essential for cell survival.
Objective To demonstrate the protective effect of resveratrol(RES)on the hepatic function in rats... more Objective To demonstrate the protective effect of resveratrol(RES)on the hepatic function in rats with severe acute pancreatitis(SAP).Methods Ninety-six male Sprague-Dawley(SD)rats were randomly divided into four groups:sham-operation(SO)group,SAP group,dexamethasone-treated(DEX)group and resveratrol-treated(RES)group,each group having 24 rats which were evaluated at 3,6,and 12 h during the experiment.Serum hepatic function was determined by biochemical detection.Serum TNF-α and IL-6 levels were determined by ELISA.The ultrastructure of hepatic and pancreatic tissues was observed by transmission electron microscope.The expressions of the apoptosis-related genes and proteins Bcl-2,Bax caspase-3 and cytochrome C were observed using semi-quantitative RT-PCR and Western blot techniques respectively.Results The serum aspartate aminotransferase,alanine aminotransferase and total bilirubin levels were significantly higher in SAP group than in SO group.The levels of AST,ALT and TBIL in RES group were lower than those in SAP group at all the time points(P0.05),while there was no statistical significance between RES and DEX groups at any time points(P0.05).The serum TNF-α and IL-6 levels were higher in SAP group than in both RES group and DEX group(P0.05).In SAP group,pancreatic and hepatic congestion,edema,inflammatory cell infiltration,mitochondrial swelling and cell apoptosis were apparent.In RES group and DEX group,pancreatic and hepatic morphological changes were alleviated at all the time points.In both RES and DEX groups,the mitochondrial membranous electric potential of hepatocytes was higher than in SAP group at any time point(P0.05).In comparison with those in SAP group,the expressions of Bcl-2 increased,whereas the expression of Bax,caspase-3 and cytochrome c decreased significantly in RES group(P0.05).The results of Western blot and RT-PCR were consistent,and no significant differences were found in all the indicators between RES group and DEX group.Conclusion Resveratrol could decrease hepatic cell apoptosis and improve hepatic injury in SAP rats.
Comparison of Mycobacterium tuberculosis with Escherichia coli reveals a reduction in the diversi... more Comparison of Mycobacterium tuberculosis with Escherichia coli reveals a reduction in the diversity of DNAmanaging proteins, such as DNA topoisomerases, although genome sizes are similar for the two species. The same is true for nucleoid-associated proteins (NAPs), important factors in bacterial chromosome compaction, chromosome remodeling, and regulation of gene expression. In a search for still uncharacterized NAPs, we found that M. tuberculosis protein Rv0430 has NAP-like features: it binds to DNA in a length-and supercoil-dependent fashion, prefers A/T-rich DNA sequences, protects DNA from damaging agents, and modulates DNA supercoiling. At a ratio of 1 dimer/40 bps of DNA, Rv0430 bridges distant DNA segments; at 1 dimer/20 bps, it coats DNA, forming inflexible rods. Rv0430 also stimulates the DNA relaxation activity of topoisomerase I. Remarkably, Rv0430 stimulates its own promoter in a supercoil-dependent manner. It is the first gene of an operon harboring two regulators of M. tuberculosis virulence (virR and sodC), and controls the expression of these downstream virulence regulators and therefore itself is a virulence regulator. The sensitivity of rv0430 expression to supercoiling is consistent with supercoiling being important for infection by M. tuberculosis. Thus, Rv0430 is a novel NAP, doubling up as a topology modulator of M. tuberculosis.
Background: Gangrenous cystitis is an extremely rare condition with very few cases reported in li... more Background: Gangrenous cystitis is an extremely rare condition with very few cases reported in literature. Diagnosis is often delayed due to the nonspecifi c symptoms. A multidisciplinary team approach and surgical debridement is usually required for management. Case presentation: This case reports a 27 year old female who developed gangrenous cystitis postpartum. She was managed with partial cystectomy and primary closure of urinary bladder. Conclusion: Gangrenous cystitis is a condition with high morbidity and mortality. A high index of suspicion is necessary for diagnosis.
Journal of College of Medical Sciences-nepal, Dec 28, 2015
INTRODUCTION Injury to Anterior Cruciate Ligament (ACL) reconstruction has increased because of i... more INTRODUCTION Injury to Anterior Cruciate Ligament (ACL) reconstruction has increased because of increased interest in sports. Rupture of ACL may lead to instability, pain, swelling, mechanical dysfunction and an increased risk of meniscal injury and degenerative changes. 1-5 Non operative treatment may lead to suboptimal knee function and to joint detoriation. 4,6,7 For this reason many procedures have been developed to restore stability and allow patient to have more active life. The reconstruction of ACL with central third of patellar tendon with proximal and distal bone blocks has been shown to produce dependable results. 2,8 The fixation of these grafts is most commonly performed with metal or bioabsorbable interference screw. This procedure is well
Cases of extra uterine translocation of intrauterine contraceptive device (IUCD) to adjacent stru... more Cases of extra uterine translocation of intrauterine contraceptive device (IUCD) to adjacent structures like peritoneal cavity, urinary bladder & sigmoid colon have been reported. Here is a case of translocation of IUCD into the caecum presenting as appendicitis. Appendicitis resulting from IUCD translocation is very rare. As per our knowledge only 19 cases have been reported earlier.
Introduction: There are ways to operate for herniated cervical disc starting from simple discecto... more Introduction: There are ways to operate for herniated cervical disc starting from simple discectomy to artificial disc replacement. Methods and Materials: This is a prospective study of anterior cervical discectomy and fusion with polyetheretherketone (PEEK) age device conducted from January 2016 to September 2019. Age, sex ratio, level of disc prolapses, symptoms, complications of surgery and the outcome was assessed. Neurological assessment was done pre and postoperatively as defined by Odom's criteria and Ranawat et al grading system. Check x-ray was done at three and six months. Results: The total number of cases was 82, predominantly males (62%). Disc prolapse due to degenerative disease was the most common case (68%). C5-6 was the most often disc prolapse level (40%), followed by C6-7 level (38%) and multiple level disc prolapse in 12%. Applying Ranawat grading system of neurological deficit; at presentation, majority were in Grade II (54%), followed by Grade IIIA (19%). Postoperatively there was reduction in weakness from 54% to 16% in Grade II and from 19% to 8% for Grade IIIA. Majority had excellent and good outcome based on Odom's criteria. The continuity of the graft and the adjacent spinal curvature was also assessed and there was more than 96% fusion rate. Conclusion: Use of local autograft with a PEEK cage has a benefit of working within the same operative window as the ACDF, thus reducing the infection, bleeding, and pain risks that may be encountered with a second incision. It is very safe to use in single level or multilevel cervical disc prolapse and also saves additional time of harvesting graft from the donor site.
Journal of International Medical Research, Apr 1, 2022
ObjectiveTo investigate the effects of piperlongumine (PL) and vitamin C (VC) on signal transduce... more ObjectiveTo investigate the effects of piperlongumine (PL) and vitamin C (VC) on signal transducer and activator of transcription 3 (STAT3) signalling in gastric cancer cell lines.MethodsIn vivo tumour xenograft anticancer assays were undertaken to confirm the anticancer activity of PL. Cell viability, flow cytometry and Western blot assays were undertaken to evaluate the anticancer effects of PL, VC and combinations of PL and VC in AGS and KATO III cells.ResultsBoth PL and VC induced apoptosis and inhibited cell proliferation in AGS and KATO III cells. These effects were dependent on reactive oxygen species (ROS). PL effectively suppressed STAT3 activation while VC caused abnormal activation of STAT3. The combination of PL and VC exhibited a stronger apoptotic effect compared with either agent alone. PL reversed the abnormal activation of STAT3 by VC, which could be a key to their synergistic effect.ConclusionsPL combined with VC exhibited a stronger anticancer effect by regulating the ROS–STAT3 pathway, suggesting that this combination might be a potential adjuvant therapy for gastric cancer.
The long-noncoding RNAs (lncRNAs) have been identified as key players in diverse cellular process... more The long-noncoding RNAs (lncRNAs) have been identified as key players in diverse cellular processes in non-small cell lung cancer (NSCLC). However, the understanding of biological functions and detailed mechanisms of lncRNAs is still limited. Herein, the lncRNA cancer susceptibility candidate 9 (CASC9) on NSCLC progression is investigated. Materials and Methods: Expressions of CASC9, HuR and cell division cycle 6 (CDC6) in NSCLC tissues were detected with quantitative real-time polymerase chain reaction (qRT-PCR). The cell counting kit-8, transwell assays, and flow cytometry were used to examine cell proliferation, migration, and the cell cycle. Tumor growth in vivo was evaluated by xenograft tumor experiments and immunohistochemistry. RNA-binding protein immunoprecipitation (RIP) was used to identify the interaction between HuR and CDC6, and CASC9 and HuR. Results: CASC9, CDC6 and HuR expression were found significantly upregulated in NSCLC tissues, which predicted poorer 5-year overall survival in NSCLC patients. Inhibition of CASC9 significantly reduced the malignancy of NSCLC cells, such as proliferation, migration and cell cycle. In vivo experiments further demonstrated that CASC9 knockdown reduced the tumor growth and the Ki-67 expression. Moreover, CASC9 knockdown inhibited the expression of CDC6 which was detected overexpressed in NSCLC tumor tissues. Then, up-regulation of CDC6 could partly reverse the negative effects of CASC9 on cell proliferation, migration and cell cycle. RIP assay and rescue experiment showed that CASC9 regulated CDC via binding to HuR. Conclusion: Our results indicate that CASC9 conferred an aggressive phenotype in NSCLC and might be a pivotal target for this disease.
C yr61 is a 42 kDa secreted protein from CCN-family, containing four different conserved molecula... more C yr61 is a 42 kDa secreted protein from CCN-family, containing four different conserved molecular domains. Overproduction of Cyr61/CCN1 plays a critical role in the development and progression of pancreatic cancer, through the induction of EMT and stemness. Pancreatic cancer stem cells (PCSC) are rare tumour cells characterized by their ability to self-renew, and are responsible for tumour recurrence accompanied by resistance to current therapies. Shh pathway is highly activated in pancreatic CSCs and plays important role in maintaining stemness by regulating the expression of stemness genes. Cyr61 expression has been found to be exorbitantly higher in cancer stem/tumour initiating Panc-1-side-population (SP) cells. Cyr61/CCN1 silencing in pancreatic CSCs results in reduced aggressive behaviour, reversing of the EMT, blocking of the expression of stem-cell-like traits and inhibition in migration. In contrast, addition of Cyr61 protein in culture medium augments EMT and stemness features in relatively less aggressive BxPC3 pancreatic cancer cells. The objective of this study is to investigate the role of CCN1 & Shh pathway in pancreatic cancer and to examine the molecular mechanisms by which CCN1 acts as a regulator for Shh pathway. Another objective of this study is to examine the molecular mechanisms by which resveratrol inhibits stem cell characteristics of pancreatic CSCs derived from human primary tumours and KrasG12D transgenic mice. Hence, this study aims to identify the role of CCN1 in pancreatic cancer and the possibility of resveratrol to be used as a therapeutic agent.
Abdominal complications after placement of ventriculoperitoneal (VP) shunt are commonly reported ... more Abdominal complications after placement of ventriculoperitoneal (VP) shunt are commonly reported but asymptomatic bowel perforation with enterocutaneous fistula (ECF) is rare. This case describes a young male patient who underwent VP shunt for hydrocephalus 10 years ago. He presented with ECF due to the non-functioning abdominal end of the shunt. Patient was managed with laparotomy with fistulectomy with bowel resection and anastomosis. ECF is a rare complication of VP shunt.
Spontaneous regression of cerebral arteriovenous malformation is rare and less than hundred cases... more Spontaneous regression of cerebral arteriovenous malformation is rare and less than hundred cases have been reported in literature. The authors report a case of 64 year/male who was diagnosed with cerebral arteriovenous malformation which was found to undergo spontaneous regression on repeat imaging. Spontaneous regression of a cerebral arteriovenous malformation is a rare phenomenon.
Herein, we characterize the cellular uptake of a DNA structure generated by rolling circle DNA am... more Herein, we characterize the cellular uptake of a DNA structure generated by rolling circle DNA amplification. The structure, termed nanoflower, was fluorescently labeled by incorporation of ATTO488-dUTP allowing the intracellular localization to be followed. The nanoflower had a hydrodynamic diameter of approximately 300 nanometer and was nontoxic for all mammalian cell lines tested. It was internalized specifically by mammalian macrophages by phagocytosis within a few hours resulting in specific compartmentalization in phagolysosomes. Maximum uptake was observed after eight hours and the nanoflower remained stable in the phagolysosomes with a half-life of 12 h. Interestingly, the nanoflower co-localized with both Mycobacterium tuberculosis and Leishmania infantum within infected macrophages although these pathogens escape lysosomal degradation by affecting the phagocytotic pathway in very different manners. These results suggest an intriguing and overlooked potential application of DNA structures in targeted treatment of infectious diseases such as tuberculosis and leishmaniasis that are caused by pathogens that escape the human immune system by modifying macrophage biology.
Topoisomerases maintain topological homeostasis of bacterial chromosomes by catalysing changes in... more Topoisomerases maintain topological homeostasis of bacterial chromosomes by catalysing changes in DNA linking number. The resolution of RNA entanglements occurring in the cell would also require catalytic action of topoisomerases. We describe RNA topoisomerase and hydrolysis activities in DNA topoisomerase I (topo I) from mycobacteria. The interaction of topo I with mRNA, tRNA and rRNA suggested its role in some aspect of RNA metabolism; the enzyme participates in rRNA maturation via its RNA hydrolysis activity. Accumulation of rRNA precursors in a topo I knockdown strain and the rescue of rRNA processing deficiency in RNaseE knockdown cells by topo I expression indicated the enzyme's backup support to RNases involved in rRNA processing. We demonstrate that the active-site tyrosine of the enzyme mediates catalytic reactions with both DNA/RNA substrates, and RNA topoisomerase activity can follow two reaction paths in contrast to its DNA topoisomerase activity. Mutation in the canonical proton relay pathway impacts DNA topoisomerase activity whilst retaining activity on RNA substrates. The mycobacterial topo I thus exemplifies the resourcefulness and parsimony of biological catalysis in harnessing the limited chemical repertoire at its disposal to find common solutions to mechanistically related challenges of phosphodiester breakage/exchange reactions in DNA and RNA that are essential for cell survival.
Objective To demonstrate the protective effect of resveratrol(RES)on the hepatic function in rats... more Objective To demonstrate the protective effect of resveratrol(RES)on the hepatic function in rats with severe acute pancreatitis(SAP).Methods Ninety-six male Sprague-Dawley(SD)rats were randomly divided into four groups:sham-operation(SO)group,SAP group,dexamethasone-treated(DEX)group and resveratrol-treated(RES)group,each group having 24 rats which were evaluated at 3,6,and 12 h during the experiment.Serum hepatic function was determined by biochemical detection.Serum TNF-α and IL-6 levels were determined by ELISA.The ultrastructure of hepatic and pancreatic tissues was observed by transmission electron microscope.The expressions of the apoptosis-related genes and proteins Bcl-2,Bax caspase-3 and cytochrome C were observed using semi-quantitative RT-PCR and Western blot techniques respectively.Results The serum aspartate aminotransferase,alanine aminotransferase and total bilirubin levels were significantly higher in SAP group than in SO group.The levels of AST,ALT and TBIL in RES group were lower than those in SAP group at all the time points(P0.05),while there was no statistical significance between RES and DEX groups at any time points(P0.05).The serum TNF-α and IL-6 levels were higher in SAP group than in both RES group and DEX group(P0.05).In SAP group,pancreatic and hepatic congestion,edema,inflammatory cell infiltration,mitochondrial swelling and cell apoptosis were apparent.In RES group and DEX group,pancreatic and hepatic morphological changes were alleviated at all the time points.In both RES and DEX groups,the mitochondrial membranous electric potential of hepatocytes was higher than in SAP group at any time point(P0.05).In comparison with those in SAP group,the expressions of Bcl-2 increased,whereas the expression of Bax,caspase-3 and cytochrome c decreased significantly in RES group(P0.05).The results of Western blot and RT-PCR were consistent,and no significant differences were found in all the indicators between RES group and DEX group.Conclusion Resveratrol could decrease hepatic cell apoptosis and improve hepatic injury in SAP rats.
Comparison of Mycobacterium tuberculosis with Escherichia coli reveals a reduction in the diversi... more Comparison of Mycobacterium tuberculosis with Escherichia coli reveals a reduction in the diversity of DNAmanaging proteins, such as DNA topoisomerases, although genome sizes are similar for the two species. The same is true for nucleoid-associated proteins (NAPs), important factors in bacterial chromosome compaction, chromosome remodeling, and regulation of gene expression. In a search for still uncharacterized NAPs, we found that M. tuberculosis protein Rv0430 has NAP-like features: it binds to DNA in a length-and supercoil-dependent fashion, prefers A/T-rich DNA sequences, protects DNA from damaging agents, and modulates DNA supercoiling. At a ratio of 1 dimer/40 bps of DNA, Rv0430 bridges distant DNA segments; at 1 dimer/20 bps, it coats DNA, forming inflexible rods. Rv0430 also stimulates the DNA relaxation activity of topoisomerase I. Remarkably, Rv0430 stimulates its own promoter in a supercoil-dependent manner. It is the first gene of an operon harboring two regulators of M. tuberculosis virulence (virR and sodC), and controls the expression of these downstream virulence regulators and therefore itself is a virulence regulator. The sensitivity of rv0430 expression to supercoiling is consistent with supercoiling being important for infection by M. tuberculosis. Thus, Rv0430 is a novel NAP, doubling up as a topology modulator of M. tuberculosis.
Uploads
Papers by RAJIV JHA