Background and Objectives: Sarco/endoplasmic reticulum Ca2＋-ATPase (SERCA) inhibition was proved in streptozotocin (STZ)-diabetic rats. The present study aimed at investigating and comparing the therapeutic effect of bone marrow mesenchymal stem cells (BMMSCs), BMMSCs combined with ascorbic acid (AA) and SERCA1a gene transfected BMMSCs in induced type I diabetic myopathy of male albino rat. Methods: and Results: 54 rats were divided into donor group of 6 rats for isolation, propagation and characterization of BMMSCs and SERCA1a transfected BMMSCs, groups I∼V 48 rats. Group I of 8 control rats, group II (Diabetic) of 10 rats given STZ 50 mg/kg intraperitoneal, group III (BMMSCs) of 10 rats given STZ and BMMSCs intravenous (IV), group IV (BMMSCs and AA) of 10 rats given STZ, BMMSCs IV and AA 500 mg/kg and group V (SERCA 1a transfected BMMSCs) of 10 rats given STZ and SERCA1a transfected BMMSCs IV. The rats were sacrificed after 8 weeks. Gastrocnemius specimens were subjected to biochemical, histological, morphometric and statistical studies. Diabetic rats revealed inflammatory and degenerative muscle changes, a significant increase in blood glucose level, mean DNA fragmentation and mean MDA values and a significant decrease in mean GSH and catalase values, area of pale nuclei, area% of CD105 and CD34 ＋ve cells, SERCA1a protein and gene values. The morphological changes regressed by therapy. In group III significant decrease in DNA fragmentation and MDA, significant increase in GSH and catalase, significant increase in the mean area of pale nuclei, area % of CD105 and CD34 ＋ve cells versus diabetic group. In group IV, same findings as group III versus diabetic and BMMSCs groups. In group V, same findings as group IV versus diabetic and treated groups. Western blot and PCR proved a mean value of SERCA1a protein and gene comparable to the control group. Mean calcium concentration values revealed a significant increase in the diabetic group, in BMMSCs and AA group versus control and SERCA1a group. Conclusions SERCA1a transfected BMMSCs proved a definite therapeutic effect, more remarkable than BMMSCs combined with AA. This effect was evidenced histologically and confirmed by significant changes in the biochemical tests indicating oxidative stress, muscle calcium concentration, morphometric parameters and PCR values of SERCA1a.

Tissue factor (TF) activates the coagulation system and has an important role in the pathogenesis of various diseases. Our previous study stated that retinoid receptors (RAR-α and RXR-α) are released as a lipid droplet in monocrotaline/ lipopolysaccharide-induced idiosyncratic liver toxicity in mice. Herein, the interdependence between the release of retinoid receptors RAR-α and RXR-α and TF in Nacetyl-p-aminophenol (APAP)-induced mice liver toxicity, is investigated. Serum alanine transaminase (ALT) level, platelet and white blood cells (WBCs) counts, protein expression of fibrin, TF, cyclin D1 and cleaved caspase-3 in liver tissues are analyzed. In addition, histopathological evaluation and survival study are also performed. The results indicate that using of TF-antisense (TF-AS) deoxyoligonucleotide (ODN) injection (6 mg/kg), to block TF protein synthesis, significantly restores the elevated level of ALT and WBCs and corrects thrombocytopenia in mice injected with APAP. TF-AS prevents the peri-central overexpression of liver TF, fibrin, cyclin D1 and cleaved caspase-3. The release of RXR-α and RAR-α droplets, in APAP treated sections, is inhibited upon treatment with TF-AS. In conclusion, the above findings designate that the released RXR-α and RAR-α in APAP liver toxicity is TF dependent. Additionally, the enhancement of cyclin D1 to caspase-3-dependent apoptosis can be prevented by blocking of TF protein synthesis.

Tissue factor (TF) activates the coagulation system and has an important role in the pathogenesis of various diseases. Our previous study stated that retinoid receptors (RAR-α and RXR-α) are released as a lipid droplet in monocrotaline/ lipopolysaccharide-induced idiosyncratic liver toxicity in mice. Herein, the interdependence between the release of retinoid receptors RAR-α and RXR-α and TF in Nacetyl-p-aminophenol (APAP)-induced mice liver toxicity, is investigated. Serum alanine transaminase (ALT) level, platelet and white blood cells (WBCs) counts, protein expression of fibrin, TF, cyclin D1 and cleaved caspase-3 in liver tissues are analyzed. In addition, histopathological evaluation and survival study are also performed. The results indicate that using of TF-antisense (TF-AS) deoxyoligonucleotide (ODN) injection (6 mg/kg), to block TF protein synthesis, significantly restores the elevated level of ALT and WBCs and corrects thrombocytopenia in mice injected with APAP. TF-AS prevents the peri-central overexpression of liver TF, fibrin, cyclin D1 and cleaved caspase-3. The release of RXR-α and RAR-α droplets, in APAP treated sections, is inhibited upon treatment with TF-AS. In conclusion, the above findings designate that the released RXR-α and RAR-α in APAP liver toxicity is TF dependent. Additionally, the enhancement of cyclin D1 to caspase-3-dependent apoptosis can be prevented by blocking of TF protein synthesis.

Background/Aims: Endoscopic ultrasound (EUS)-guided pancreatic duct drainage is a well-established procedure for managing pancreaticojejunostomy anastomotic strictures (PJAS) post-Whipple surgery. In this study, we examined the effectiveness and safety of EUS-guided pancreaticojejunostomy (EUS-PJS). Methods: This retrospective, single-arm study was performed at Aichi Cancer Center Hospital on 10 patients who underwent EUS-guided pancreaticojejunostomy through the afferent jejunal loop using a forward-viewing echoendoscope when endoscopic retrograde pancreatography failed. Our primary endpoint was technical success rate, defined as successful stent insertion. The secondary endpoints were early and late adverse events. Results: A total of 10 patients underwent EUS-PJS between February 2019 and October 2023. The technical success rate was 100%. The median procedure time was 23.5 minutes. No remarkable early or late adverse events related to the procedure, except for fever, occurred in two patients. The median follow-up duration was 9.5 months, and the median number of stent exchanges was two. A stent-free state was achieved in three patients. Conclusions EUS-PJS for PJAS management after pancreaticoduodenectomy appears to be an effective and safe procedure with the potential advantages of fewer reinterventions and the creation of a permanent drainage fistula.

Background/Aims: Biliary obstruction drainage in patients with hepatocellular carcinoma (HCC) is associated with symptom palliation, improved access to chemotherapy, and improved survival. Stent placement and exchange via endoscopic retrograde cholangiopancreatography biliary drainage risk traversing the HCC, a hypervascular tumor and causing bleeding. Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) potentially prevents procedure-related bleeding. Therefore, we evaluated the efficacy and safety of EUS-HGS as an alternative treatment for biliary obstruction in patients with HCC. Methods: This was a retrospective study of all EUS-HGS procedures performed in patients with HCC at the Aichi Cancer Center Hospital, Japan, from February 2017 to August 2023. Results: A total of 14 EUS-HGS procedures (42.9% primary) were attempted in 10 HCC patients (mean age 71.5 years, 80.0% male). Clinical and technical success rates were 92.9% and 90.9%, respectively. The observed procedure details in the 13 successful procedures included B3 puncture (53.8%), 22-G needle (53.8%), fully covered self-expandable metal stent (100%), and mean procedure time (32.7 minutes). There was no bleeding. Mild complications occurred in 27.3%. All patients resumed oral intake within 24 hours. Conclusions EUS-HGS is a technically feasible and clinically effective initial or salvage drainage option for the treatment of biliary obstruction in patients with HCC.

Background/Aims: Endoscopic ultrasound (EUS)-guided pancreatic duct drainage is a well-established procedure for managing pancreaticojejunostomy anastomotic strictures (PJAS) post-Whipple surgery. In this study, we examined the effectiveness and safety of EUS-guided pancreaticojejunostomy (EUS-PJS). Methods: This retrospective, single-arm study was performed at Aichi Cancer Center Hospital on 10 patients who underwent EUS-guided pancreaticojejunostomy through the afferent jejunal loop using a forward-viewing echoendoscope when endoscopic retrograde pancreatography failed. Our primary endpoint was technical success rate, defined as successful stent insertion. The secondary endpoints were early and late adverse events. Results: A total of 10 patients underwent EUS-PJS between February 2019 and October 2023. The technical success rate was 100%. The median procedure time was 23.5 minutes. No remarkable early or late adverse events related to the procedure, except for fever, occurred in two patients. The median follow-up duration was 9.5 months, and the median number of stent exchanges was two. A stent-free state was achieved in three patients. Conclusions EUS-PJS for PJAS management after pancreaticoduodenectomy appears to be an effective and safe procedure with the potential advantages of fewer reinterventions and the creation of a permanent drainage fistula.

Background/Aims: Biliary obstruction drainage in patients with hepatocellular carcinoma (HCC) is associated with symptom palliation, improved access to chemotherapy, and improved survival. Stent placement and exchange via endoscopic retrograde cholangiopancreatography biliary drainage risk traversing the HCC, a hypervascular tumor and causing bleeding. Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) potentially prevents procedure-related bleeding. Therefore, we evaluated the efficacy and safety of EUS-HGS as an alternative treatment for biliary obstruction in patients with HCC. Methods: This was a retrospective study of all EUS-HGS procedures performed in patients with HCC at the Aichi Cancer Center Hospital, Japan, from February 2017 to August 2023. Results: A total of 14 EUS-HGS procedures (42.9% primary) were attempted in 10 HCC patients (mean age 71.5 years, 80.0% male). Clinical and technical success rates were 92.9% and 90.9%, respectively. The observed procedure details in the 13 successful procedures included B3 puncture (53.8%), 22-G needle (53.8%), fully covered self-expandable metal stent (100%), and mean procedure time (32.7 minutes). There was no bleeding. Mild complications occurred in 27.3%. All patients resumed oral intake within 24 hours. Conclusions EUS-HGS is a technically feasible and clinically effective initial or salvage drainage option for the treatment of biliary obstruction in patients with HCC.

Background/Aims: Endoscopic ultrasound (EUS)-guided pancreatic duct drainage is a well-established procedure for managing pancreaticojejunostomy anastomotic strictures (PJAS) post-Whipple surgery. In this study, we examined the effectiveness and safety of EUS-guided pancreaticojejunostomy (EUS-PJS). Methods: This retrospective, single-arm study was performed at Aichi Cancer Center Hospital on 10 patients who underwent EUS-guided pancreaticojejunostomy through the afferent jejunal loop using a forward-viewing echoendoscope when endoscopic retrograde pancreatography failed. Our primary endpoint was technical success rate, defined as successful stent insertion. The secondary endpoints were early and late adverse events. Results: A total of 10 patients underwent EUS-PJS between February 2019 and October 2023. The technical success rate was 100%. The median procedure time was 23.5 minutes. No remarkable early or late adverse events related to the procedure, except for fever, occurred in two patients. The median follow-up duration was 9.5 months, and the median number of stent exchanges was two. A stent-free state was achieved in three patients. Conclusions EUS-PJS for PJAS management after pancreaticoduodenectomy appears to be an effective and safe procedure with the potential advantages of fewer reinterventions and the creation of a permanent drainage fistula.

Background/Aims: Biliary obstruction drainage in patients with hepatocellular carcinoma (HCC) is associated with symptom palliation, improved access to chemotherapy, and improved survival. Stent placement and exchange via endoscopic retrograde cholangiopancreatography biliary drainage risk traversing the HCC, a hypervascular tumor and causing bleeding. Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) potentially prevents procedure-related bleeding. Therefore, we evaluated the efficacy and safety of EUS-HGS as an alternative treatment for biliary obstruction in patients with HCC. Methods: This was a retrospective study of all EUS-HGS procedures performed in patients with HCC at the Aichi Cancer Center Hospital, Japan, from February 2017 to August 2023. Results: A total of 14 EUS-HGS procedures (42.9% primary) were attempted in 10 HCC patients (mean age 71.5 years, 80.0% male). Clinical and technical success rates were 92.9% and 90.9%, respectively. The observed procedure details in the 13 successful procedures included B3 puncture (53.8%), 22-G needle (53.8%), fully covered self-expandable metal stent (100%), and mean procedure time (32.7 minutes). There was no bleeding. Mild complications occurred in 27.3%. All patients resumed oral intake within 24 hours. Conclusions EUS-HGS is a technically feasible and clinically effective initial or salvage drainage option for the treatment of biliary obstruction in patients with HCC.

Background/Aims: Dilation of the tract before stent deployment is a challenging step in endoscopic ultrasound-guided pancreatic duct drainage (EUS-PDD). In this study, we examined the effectiveness and safety of a novel spiral dilator, Tornus ES (Asahi Intec), for EUS-PDD. Methods: This was a retrospective, single-arm, observational study at Aichi Cancer Center Hospital. The punctured tract was dilated using a Tornus ES dilator in all EUS-PDD cases. Our primary endpoint was the technical success rate of initial tract dilation. Technical success was defined as successful fistula dilation using a Tornus ES followed by successful stent insertion. Secondary endpoints were procedure times and early adverse events. Results: A total of 12 patients were included between December 2021 and March 2023. EUS-PDD was performed in 11 patients for post-pancreaticoduodenectomy anastomotic strictures and one patient with pancreatitis with duodenal perforation. The technical success rates of stent insertion and fistula dilation using a Tornus ES dilator was 100%. The median procedure time was 24 minutes. No remarkable adverse events related to the procedure were observed, apart from fever, which occurred in 2 patients. Conclusions Tract dilation in EUS-PDD using a Tornus ES is effective and safe.