Ex vivo kidney machine perfusion: meta-analysis of randomized clinical trials.

BACKGROUND: Machine perfusion is an organ preservation strategy used to improve function over simple storage in a cold environment. This article presents an updated systematic review and meta-analysis of machine perfusion in deceased donor kidneys. METHODS: RCTs from November 2018 to July 2023 comparing machine perfusion versus static cold storage in kidney transplantation were evaluated for systematic review. The primary outcome in meta-analysis was delayed graft function. RESULTS: A total 19 studies were included, and 16 comparing hypothermic machine perfusion with static cold storage were analysed. The risk of delayed graft function was lower with hypothermic machine perfusion (risk ratio (RR) 0.77, 95% c.i. 0.69 to 0.86), even in kidneys after circulatory death (RR 0.78, 0.68 to 0.90) or brain death (RR 0.73, 0.63 to 0.84). Full hypothermic machine perfusion decreased the risk of delayed graft function (RR 0.69, 0.60 to 0.79), whereas partial hypothermic machine perfusion did not (RR 0.92, 0.69 to 1.22). Normothermic machine perfusion or short-term oxygenated hypothermic machine perfusion preservation after static cold storage was equivalent to static cold storage in terms of delayed graft function and 1-year graft survival. CONCLUSION: Hypothermic machine perfusion reduces delayed graft function risks and normothermic approaches show promise.

Ambient air pollution and the risk of neurological diseases in residential areas near multi-purposed industrial complexes of korea: A population-based cohort study.

Emerging evidence suggest that long-term exposure to air pollution may induce adverse effects on the central nervous system. However, no study explored the associations in large industrial complex (IC) areas which are one of the major contributors to air pollution. Therefore, we aimed to investigate the pollution status and the association between residential proximity and incidence of neurological diseases near two major ICs characterized as multi-purposed ICs in Korea. A retrospective cohort of residents near the ICs was constructed using Korea's health insurance data and monitored from 2008 to 2019. Emission amounts of the ICs and the air pollution status in the nearby (exposed) and remote (control) area were evaluated using data from national regulatory networks, and hazard ratios (HRs) and 95% confidence intervals (CIs) for neurological diseases of the exposed group compared to the control group were calculated using Cox proportional regression models. Overall, the complexes emitted large amounts of VOCs, CO, NOx, and PM10, and annual levels of ambient PM (2.5, 10), gaseous substances (NO2, SO2), VOCs and PAHs were higher in the exposed area compared to the control and/or the national average. The risk of inflammatory disease of the CNS (G00-09) and extrapyramidal and movement disorders (G20-26) were higher in the exposed area with a HR (95% CI) of 1.36 (1.10-1.68) and 1.33 (1.27-1.39) respectively. Among the subclasses, other extrapyramidal and movement disorders (G25) and epilepsy (G40) were associated with higher risks in the exposed area (HR (95%CI): 1.11 (1.04-1.18), 1.08 (1.00-1.16)) after adjusting for potential confounders. These results suggest that people living near ICs are more likely to be exposed to higher air pollution levels and have higher risks of developing several neurological disorders. However, further epidemiological studies in these industrial areas supplemented with other indicators of environmental exposure and control of other diverse factors are warranted.

Safety of laparoscopic surgery during pregnancy: a Korean nationwide population-based study.

BACKGROUND: The optimal surgical approach to perform during pregnancy is still controversial. This study evaluated pregnancy and operative outcomes in women undergoing an appendectomy or cholecystectomy during pregnancy, and compared them between the laparoscopic and open approach using nationwide population-based data. METHODS: Between 2009 and 2019, a total of 2941 pregnant women with procedure codes for an appendectomy or cholecystectomy were extracted from the Korean National Health Insurance claims data (laparoscopy: 1504; open: 1437). Surgical outcomes [length of stay (LOS), anesthesia time, 30-day readmission rates, transfusion rates, second laparotomy, and 30-day mortality rates] and pregnancy outcomes (live birth rate, overall and spontaneous abortion rates, threatened abortion rate, type of delivery, preterm labor, stillbirth, fetal screening abnormalities, and intrauterine growth retardation) were compared between the open and laparoscopic groups. RESULTS: The laparoscopic group had a significantly shorter LOS than the open group, and transfusions were less frequent in the laparoscopic group. Mortality, 30-day readmission rates, and second laparotomy were not statistically significant between the two groups. There were no significant differences in fetal loss and live birth rates between the two groups in all gestational ages. Preterm labor within 30 days of surgery was more frequent in the laparoscopy group than in the open surgery group, especially for those in their first and third trimesters. Open procedures were associated with an increased rate of cesarean sections. CONCLUSIONS: Laparoscopic surgery was found to be feasible and safe without adverse postoperative outcomes. Careful observation of postoperative preterm labor is necessary, especially for women who undergo laparoscopic surgery in their first and third trimesters.

Pneumocystis pneumonia occurrence and prophylaxis duration in kidney transplant recipients according to perioperative treatment with rituximab.

BACKGROUND: Pneumocystis pneumonia (PCP) is a life-threatening fungal infection that can occur in kidney transplantation (KT) recipients. A growing number of KT recipients are receiving perioperative treatment with rituximab, which is associated with prolonged B-cell depletion and possible risk of PCP occurrence; however, the optimal prophylaxis duration according to rituximab treatment is yet unknown. We compared the occurrence of PCP and the duration of prophylaxis in KT recipients according to rituximab treatment. METHODS: We retrospectively analyzed 2110 patients who underwent KT between January 2009 and December 2016, who were divided into non-Rituximab group (n = 1588, 75.3%) and rituximab group (n = 522, 24.7%). RESULTS: In the rituximab group, the estimated number needed to treat (NNT) for prophylaxis prolongation from 6 to 12 months was 29.0 with a relative risk reduction of 90.0%. In the non-rituximab group, the estimated NNT value was 133.3 and the relative risk reduction was 66.4%. Rituximab treatment (hazard ratio (HR) = 3.09; P <  0.01) and acute rejection (HR = 2.19; P = 0.03) were significant risk factors for PCP in multivariate analysis. CONCLUSIONS: Our results suggest that maintaining PCP prophylaxis for 12 months may be beneficial in KT recipients treated with rituximab for desensitization or acute rejection treatment.

Relationship of Lower-extremity Deep Venous Thrombosis Density at CT Venography to Acute Pulmonary Embolism and the Risk of Postthrombotic Syndrome.

Background Acute deep venous thrombi (DVT) have higher Hounsfield unit values than chronic (bland) thrombi at CT venography. Purpose To determine the relationship between DVT thrombus density found on CT venography images to the presence of acute pulmonary embolism (PE) and the future risk of postthrombotic syndrome (PTS) in patients with DVT. Materials and Methods In this retrospective study, patients were divided into two groups: PE with DVT group and DVT-only group. Wells scores were recorded. Thrombus density ratios were calculated (DVT thrombus Hounsfield units/surrounding vein Hounsfield units). The presence or absence of PTS was determined from the results of the Venous Insufficiency Epidemiologic and Economic Study on Quality of Life (VEINES-QOL) questionnaires given to the patients with DVT. Statistical analyses used receiver operating characteristic curves and Spearman correlation analyses. Results Eighty-six patients were included; the mean age was 60 years ± 17 (51 men; PE with DVT group, 54 patients [63%]; DVT-only group, 32 patients [37%]). The mean thrombus density ratio was significantly higher in the PE with DVT group than in the DVT-only group (53.6% ± 12.4 [standard deviation] vs 42.8% ± 11.9, respectively; P < .001). At multivariable analysis, Wells score greater than 4 (odds ratio, 12.0; 95% confidence interval [CI]: 3.0, 47; P < .001) and higher thrombus density ratio (odds ratio, 1.1; 95% CI: 1.0, 1.2; P = .001) were independent predictors of PE. The diagnostic performance for the thrombus density ratio (area under the receiver operating characteristic curve, 0.74; 95% CI: 0.63, 0.85; P < .001) may be more discriminative than that of the Wells score (area under the receiver operating characteristic curve, 0.70; 95% CI: 0.59, 0.81; P = .002) for the presence of PE. In subgroup analysis, the thrombus density ratio and VEINES-QOL score were correlated (r = 0.61; 95% CI: 0.30, 0.80; P < .001). Conclusion Deep venous thrombosis (DVT) density ratio at CT venography was associated with acute pulmonary embolism in patients with lower-extremity DVT. © RSNA, 2019 Online supplemental material is available for this article.

The results of HLA-incompatible kidney transplantation according to pre-transplant crossmatch tests: Donor-specific antibody as a prominent predictor of acute rejection.

BACKGROUND: Crossmatching (XM) between organ donors and recipients is correlated with clinical outcomes. This study evaluates the results of HLA-incompatible kidney transplant (HLA-i KT) according to pre-transplant XM modalities. METHODS: This study included 731 consecutive patients. HLA-i KT was defined as a transplant under conditions of complement-dependent cytotoxicity (CDC) XM positivity, flow-cytometric XM (FCXM) positivity, and/or maximal donor-specific antibody (DSA) mean fluorescence intensity (MFI) ≥5000. RESULTS: The incidence of antibody-mediated rejection (AMR) within 1 year after transplant was significantly higher in the HLA-i group than in the HLA compatible (HLA-c) group (15 vs 9 patients, 14.2% vs 1.4%; P < 0.01). Multivariate analysis indicated that a DSA MFI ≥5000 (odds ratio [OR] = 2.63; 95% confidence interval [CI], 1.00-6.98; P = 0.05) was significantly associated with acute rejection (AR), whereas CDC (OR = 2.09; 95% CI, 0.55-7.99; P = 0.28) and FCXM positivity (OR = 2.07; 95% CI, 0.73-5.87; P = 0.17) were not. Similarly, DSA MFI ≥ 5000 (OR = 4.14; P = 0.02) was the only significant factor affecting the risk of AMR. CONCLUSIONS: Of the various XM tests, DSA MFI ≥5000 was the most prominent predictor of AR in patients undergoing HLA-i KT.

Intracranial aneurysms in patients receiving kidney transplantation for autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, leading to kidney failure. One of the most serious extrarenal complications of ADPKD is comorbid intracranial aneurysms. The aim of this study is to evaluate the prevalence, rupture rate, and treatment outcomes of intracranial aneurysms in ADPKD. METHODS: Adult patients with a documented diagnosis of ADPKD who received kidney transplantation at our center from January 1994 to December 2018 were included in the study. Medical history, physical examination, laboratory findings, imaging studies, and operation records were collected and analyzed from our database. RESULTS: Among 154 kidney transplant recipients with ADPKD, 113 (73.4%) patients were screened for intracranial aneurysms preoperatively. Twenty three patients (14.9%) had intracranial aneurysms with mean diameter size of 4.5 ± 2.7 mm. Nine patients (5.8%) experienced aneurysm rupture and the mean age at time of rupture was 34.9 ± 9.3 years. Twelve patients (52.2%) presented with multiple aneurysms. The most common aneurysm location was the bifurcation of the middle cerebral artery (34.9%). Clipping was the most common treatment in both ruptured and unruptured aneurysms. CONCLUSIONS: Intracranial aneurysms are more frequent in patients with ADPKD, and the average age of intracranial artery rupture in patients with ADPKD is earlier than in the general population. It is necessary to consider proper evaluation and management of intracranial aneurysms when counseling ADPKD patients who will undergo kidney transplantation.

Positive regulatory role of c-Src-mediated TRIM25 tyrosine phosphorylation on RIG-I ubiquitination and RIG-I-mediated antiviral signaling pathway.

Retinoic acid-inducible gene I (RIG-I) detects viral RNAs and induces antiviral responses. During viral RNA recognition by RIG-I, tripartite motif protein 25 (TRIM25) plays a critical regulatory role by inducing K63-linked RIG-I polyubiquitination. Previous proteomics analysis revealed several phosphorylation sites on TRIM25, including tyrosine 278 (Y278), yet the roles of these modifications remain elusive. Here, we demonstrated that TRIM25 interacted with c-Src and underwent tyrosine phosphorylation by c-Src kinase upon viral infection and the phosphorylation is required for the complete activation of RIG-I signaling. Analysis using a c-Src inhibitor and TRIM25 mutant, in which tyrosine 278 is substituted by phenylalanine (Y278F), suggested that the phosphorylation positively regulates K63-linked polyubiquitination of RIG-I and subsequent antiviral signaling. The TRIM25 Y278F mutant displayed decreased E3-ubiquitin ligase activity in vitro, suggesting that this phosphorylation event affects the E3-ligase activity of TRIM25. Thus, we provide a molecular mechanism of c-Src-mediated positive regulation of RIG-I signaling.

TP53-dependence on the effect of doxorubicin and Src inhibitor combination therapy.

The anticancer effects of Src kinase inhibitors are controversial. This study found an association between alterations in the TP53 gene and the synergy score for combination treatment with doxorubicin and an Src kinase inhibitor using human osteosarcoma cell lines (MG63 and U2OS) and human colon cancer cell line. Doxorubicin was found to activate signal transducer and activator of transcription 3 via Src kinase in cancer cells harboring alterations in TP53. A drug combination study using patient-derived cells confirmed that an Src kinase inhibitor synergizes with doxorubicin in cancer cells harboring alterations in TP53, while antagonizing its effect in cancer cells expressing wild-type TP53. Our findings suggest that genetic alterations in TP53 are a critical factor in determining the use of a combination treatment of doxorubicin and Src inhibitors.

Impact of pretransplant donor-specific antibodies on kidney allograft recipients with negative flow cytometry cross-matches.

The Luminex test can detect low levels of donor-specific antibody (DSA) that cannot be detected by flow-cytometric cross-matching (FCXM) in kidney transplantation (KT). This study evaluated the impact of DSA on clinical outcomes in KT recipients negative on FCXM. Of 575 consecutive patients who underwent living donor KT between January 2013 and July 2016, 494 (85.9%) were DSA-negative and 81 (14.1%) were DSA-positive. Although rates of acute cellular rejection (ACR) at 1 year were similar in the 2 groups (P = .54), the incidence of antibody-mediated rejection (ABMR) was significantly higher in the DSA-positive group (P < .01). There was no statistically significant association between rejection-free graft survival (RFGS) rates and pretransplant class I DSA. However, evaluation of pretransplant class II DSA showed that RFGS rates were significantly lower in patients with mean fluorescence intensity (MFI) >3000 than in patients with DSA-negative (P < .01). On multivariate analyses, class II DSA MFI ≥5000 was a significant risk factor for acute rejection (hazard ratio, 7.48; P < .01). These findings suggested that pretransplant DSA alone did not affect graft survival in KT recipients without desensitization. However, class II DSA MFI >5000 was an independent predictor of acute rejection in DSA-positive patients.

Induction of mast cell degranulation by triterpenoidal saponins obtained from Cimicifugae rhizoma.

Cimicifugae rhizoma has been widely used as a traditional herbal medicine to treat inflammation and menopausal symptoms. In this study, we found that some of the triterpenoidal saponins purified from the ethanol extract of Cimicifugae rhizoma dramatically induced histamine release. The structure-related induction of mast cell degranulation by them and the mechanism of action were determined. ß-Hexosaminidase release in HMC-1 cells was increased in a concentration-dependent manner, with maximal 6.5- and 8.5-fold increases, by 200 µg/mL 24-epi-7,8-didehydrocimigenol-3-O-xyloside (comp 1) and cimigenol 3-O-beta-d-xyloside (comp 4) compared with those treated with phorbol 12-myristate 13-acetate and A23187 (PMACI), respectively. However, ß-hexosaminidase release was not changed by 7,8-dihydrocimigenol (comp 3), or 23-OAc-shengmanol-3-O-xyloside (comp 7). These triterpenoidal saponins changed neither the intracellular Ca(2+ )level nor the activation of PKC, both of which play essential roles in histamine release. However, cromolyn and ketotifen, membrane stabilizers, effectively inhibited the ß-hexosaminidase release induced by comp 1 or comp 4 by 39 and 45%, respectively. Collectively, xylose on the cimigenol-related backbone among triterpene glycosides isolated from Cimicifugae rhizoma may play an important role in activating mast cells and induction of degranulation partly via membrane destabilization of mast cells.

Interpreting CD56+ and CD163+ infiltrates in early versus late renal transplant biopsies.

BACKGROUND: CD56+ and CD163+ cell infiltration in human kidney transplant biopsies have not been fully evaluated. METHODS: We investigated the association of CD56+ and CD163+ cell infiltration with human kidney transplant biopsies with antibody- or T-cell-mediated rejection (TCMR) and other histologic lesions. One hundred and seventy four clinically indicated transplant biopsies were included in this analysis. Immunohistochemical staining for C4d, CD56 and CD163 was performed. RESULTS: One hundred and seventy four indication biopsies were divided into early (≤1 year posttransplant; n = 49) and late (>1 year posttransplant; n = 125) biopsies. High numbers of CD56+ cells were uncommon in early biopsies except for those with antibody-mediated rejection (AMR) only. On the other hand, high numbers of CD56+ cells were observed in late biopsies diagnosed as TCMR only, AMR only, and TCMR combined with AMR. In early biopsies, both CD56+ and CD163+ infiltrates correlated strongly with interstitial inflammation, tubulitis, and peritubular capillaritis (ptc) scores. The ci and ct scores, however, were correlated only with the number of CD56+ cells. In late biopsies, on the other hand, the number of CD56+ infiltrates was correlated only with ptc, while the number of CD163+ infiltrates was weakly correlated with any histologic lesion. Multivariable analyses showed that chronic active AMR and the number of CD56+ cells/10 HPF were independently associated with death-censored graft failure post-biopsy. The number of CD163+ cells was not correlated with any pathologic lesion and post-biopsy graft failure. CD56+ infiltrates were also associated with interstitial fibrosis and tubular atrophy. CONCLUSIONS: Intragraft CD56+ cell infiltrates were significantly associated with AMR and subsequent poor clinical outcomes.

Long-term impact of human leukocyte antigen mismatches combined with expanded criteria donor on allograft outcomes in deceased donor kidney transplantation.

The long-term impact of human leukocyte antigen (HLA) mismatches combined with expanded criteria donors (ECD) on clinical outcomes has not been fully evaluated in recipients of deceased donor (DD) kidney transplantations. Of 595 DD renal transplant recipients in our center between 1991 and 2011, 210 recipients (36%) had 0-3 HLA mismatches/standard criteria donor (SCD), 353 (59%) had 4-6 HLA mismatches/SCD or 0-3 HLA mismatches/ECD, and 32 (5%) had 4-6 HLA mismatches/ECD. The mortality rate was significantly highest in the patients with 4-6 HLA mismatches/ECD (p = 0.040). The most common cause of death in this group was infection (50%). There were no significant differences in overall graft survival and death-censored graft survival. The biopsy-proven acute rejection rate was significantly higher in the 4-6 HLA mismatches/ECD group (p = 0.011). Cox-regression multivariate analyses showed that 4-6 HLA mismatches plus ECD (adjusted hazard ratio [AHR], 3.2; 95% confidence interval [CI], 1.17-10.56) and diabetes (AHR, 4.3; 95% CI, 1.50-12.28) were significant predictors of recipient mortality. In conclusion, ≥4 HLA mismatches plus ECD were associated with significantly higher rates of biopsy-proven acute rejection and mortality compared with other groups undergoing DD kidney transplantation.

Comparison of surgical and endovascular salvage procedures for juxta-anastomotic stenosis in autogenous wrist radiocephalic arteriovenous fistula.

BACKGROUND: Although dysfunctional radiocephalic arteriovenous fistulas (RCAVFs) are typically treated surgically, the endovascular approach is also considered suitable. The aim of this retrospective study was to compare the cumulative patency rates following surgical and endovascular salvaging of dysfunctional RCAVFs, and to evaluate whether the maturity of vascular access sites at the time of treatment influenced the outcomes. METHODS: A total of 60 patients underwent surgical or endovascular salvage treatment for juxta-anastomotic stenosis of autogenous wrist RCAVFs: 35 patients underwent proximal neo-anastomosis and 25 underwent percutaneous transluminal angioplasty (PTA). RESULTS: Clinical and anatomical success rates were, respectively, 100% and 97.1% in the surgery group, and 100% and 96.0% in the angioplasty group (P = 0.81). The post-treatment restenosis rate was higher in the angioplasty group (n = 11, 46.0%) than in the surgery group (n = 8, 22.8%), without reaching statistical significance (P = 0.15). In a Kaplan-Meier analysis, the primary and assisted primary patency rates were significantly higher in the surgery group (P = 0.036 and P = 0.026, respectively), but there was no significant difference in secondary patency rates between the groups (P = 0.52). When stratified by RCAVF maturity at the time of treatment, no significant difference was noted in primary patency rates between the treatment groups. After adjusting for other variables, the relative risk of restenosis was significantly higher in the angioplasty group (hazard ratio 2.56; 95% confidence interval 1.02-6.46; P = 0.046). CONCLUSIONS: Post-treatment primary and assisted primary patency rates after proximal neo-anastomosis were significantly higher than after PTA, and RCAVF maturity did not influence the outcomes.

Feasibility of Extended Postoperative Follow-Up in Patients With Gastric Cancer.

Importance: Conventional research and guidelines on postgastrectomy follow-up for gastric cancer often restrict their focus to the first 5 years after surgery. Objective: To evaluate the association of extended regular follow-up after 5 years postgastrectomy in patients with gastric cancer with overall and postrecurrence survival rates. Design, Setting, and Participants: This population-based, retrospective cohort study used Korean National Health Insurance claims data extracted between January 1, 2005, and December 31, 2014, with follow-up data examined until December 31, 2021. Patients without recurrence or other cancers at 5 years postgastrectomy were divided into 2 groups: those who had extended regular follow-up visits and those who did not. The data were analyzed between August 15 and November 15, 2023. Exposures: Regular follow-up vs irregular follow-up after 5 years postgastrectomy. Main Outcomes and Measures: The main outcome was whether extended regular follow-up after 5 years postgastrectomy was independently associated with overall and postrecurrence survival rates using Cox proportional hazards regression. Postrecurrence survival rates were also compared across different follow-up methods and intervals. Results: A total of 40 468 patients with gastric cancer were included, with 14 294 in the regular follow-up group (mean [SD] age, 61.3 [11.7] years; 9669 male [67.8%]) and 26 174 in the irregular follow-up group (mean [SD] age, 58.1 [11.1] years; 18 007 male [68.8%]). Late recurrence or gastric remnant cancer (GRC) was identified in 3138 patients (7.8%), including 1610 of 40 468 patients (4.0%) between 5 and 10 years postgastrectomy and 1528 of 16 287 (9.4%) patients after 10 years postgastrectomy. Regular follow-up was associated with a significantly decreased overall mortality rate after 5 years postgastrectomy (from 49.4% to 36.9% in 15-year mortality rate; P < .001), as well as significant improvement of postrecurrence survival rate after occurrence of late recurrence or GRC (from 32.7% to 71.1% in 5-year postrecurrence survival rate; P < .001). Comparison of follow-up methods revealed that the combination of endoscopy and abdominopelvic computed tomography (CT) (only abdominopelvic CT in total gastrectomy subgroup) yielded the highest 5-year postrecurrence survival rate (endoscopy alone vs abdominopelvic CT alone vs a combination of both, 54.5% vs 47.1% vs 74.5%, respectively). A time interval of more than 2 years between previous endoscopy or abdominopelvic CT and late recurrence and GRC diagnosis was associated with a significantly reduced postrecurrence survival rate (hazard ratio, 1.72 [95% CI, 1.45-2.04] and 1.48 [95% CI, 1.25-1.75], respectively). Conclusions and Relevance: These findings suggest that extended regular follow-up after 5 years postgastrectomy should be implemented clinically and that current practice and value of follow-up protocols in postoperative care of patients with gastric cancer be reconsidered.

Novel MFSD7-ATP5I fusion promotes migration and invasion of human sarcoma.

Fusion genes have been implicated in the development and progression of several types of sarcomas, serving as valuable diagnostic and prognostic markers, as well as potential therapeutic targets. We discovered a novel major facilitator superfamily domain-containing 7 (MFSD7) and adenosine triphosphate 5I (ATP5I) gene fusion from sarcomas. In this study, the MFSD7-ATP5I fusion transcript was screened using RNA sequencing in 55 sarcoma samples and sixteen normal samples. The MFSD7-ATP5I fusion transcript was detected in 58% of sarcoma samples. The correlation between the expression of MFSD7-ATP5I fusion transcript and clinicopathological information was analyzed, and MFSD7-ATP5I expression is associated with marked pleomorphism and lower tumor necrosis. Cell migration and invasion was significantly reduced by knock-down of MFSD7-ATP5I. Cell migration and invasion was increased by overexpression of MFSD7-ATP5I. A phosphokinase assay demonstrated that MFSD7-ATP5I is involved in the GSK-3 pathway. The current study found that MFSD7-ATP5I is associated with increasing pleomorphism and decreasing necrosis of tumors. And our gain and loss of function experiments prove that MFSD7-ATP5I promotes the invasiveness of tumor cells.

BubR1 acetylation at prometaphase is required for modulating APC/C activity and timing of mitosis.

Regulation of BubR1 is central to the control of APC/C activity. We have found that BubR1 forms a complex with PCAF and is acetylated at lysine 250. Using mass spectrometry and acetylated BubR1-specific antibodies, we have confirmed that BubR1 acetylation occurs at prometaphase. Importantly, BubR1 acetylation was required for checkpoint function, through the inhibition of ubiquitin-dependent BubR1 degradation. BubR1 degradation began before the onset of anaphase. It was noted that the pre-anaphase degradation was regulated by BubR1 acetylation. Degradation of an acetylation-mimetic form, BubR1-K250Q, was inhibited and chromosome segregation in cells expressing BubR1-K250Q was markedly delayed. By contrast, the acetylation-deficient mutant, BubR1-K250R, was unstable, and mitosis was accelerated in BubR1-K250R-expressing cells. Furthermore, we found that APC/C-Cdc20 was responsible for BubR1 degradation during mitosis. On the basis of our collective results, we propose that the acetylation status of BubR1 is a molecular switch that converts BubR1 from an inhibitor to a substrate of the APC/C complex, thus providing an efficient way to modulate APC/C activity and mitotic timing.

Approaches to the management of spontaneous isolated visceral artery dissection.

BACKGROUND: Spontaneous isolated celiac and superior mesenteric artery dissection without aortic dissection is a rare disease. Recently, an increasing number of cases have been diagnosed and the prognosis has improved significantly because of technical progress in computed tomography (CT). However, management approaches vary from conservative treatment or endovascular repair to open surgery. This study analyzed the clinical findings of patients with spontaneous visceral artery dissection, and attempted to illuminate how to manage these cases. MATERIALS AND METHODS: From June 2005 to February 2012, a total of 17 patients were diagnosed with spontaneous isolated visceral artery dissection in the authors' hospital (4 celiac arteries, 12 superior mesenteric arteries, and 1 inferior mesenteric artery) based on CT findings. The clinical characteristics, Sakamoto's classification, imaging appearance, and early outcomes of these patients were retrospectively compared. RESULTS: The mean age of the patients was 51.47 ± 8.65 years (range, 39-73 years) and the mean follow-up period was 35.18 ± 25.55 months (range, 1-79 months). Fifteen (88.2%) patients had abdominal pain and no ischemic changes of the bowel. The dissections initiated at a mean distance of 13.04 ± 10.41 mm (range, 4.00-43.39 mm) from the origin of the artery, with a mean length of 53.39 ± 28.06 mm (range, 10.00-108.46 mm). There were 4 type I (23.8%), 1 type II (5.9%), 9 type III (52.9%), and 3 type IV (17.6%) dissections according to Sakamoto's classification. Treatments included observation without anticoagulation treatment in 3 patients (17.6%), anticoagulation treatment in 12 (70.6%), and endovascular stenting in 2 (11.8%). The disease stabilized in all patients during follow-up. CONCLUSIONS: If bowel perfusion is not compromised and patency is well compensated by collateral circulation, most patients can be managed conservatively with or without anticoagulation treatment. However, patients must be monitored closely and followed up regularly for early detection of progression.

Gene expression profiling of kidneys from Sprague-Dawley rats following 12-week inhalation exposure to silver nanoparticles.

The specific properties of silver nanoparticles (AgNPs), such as antimicrobial activity and electrical conductivity, allow them to be used in many fields. However, their expanding application is also raising health, environmental and safety concerns. Previous in vivo AgNP toxicity studies have indicated a gender-different accumulation of silver in the kidneys, with 2-3 times more silver in female kidneys compared to male kidneys. However, no other studies have further addressed this gender difference. Accordingly, the current study investigated the gender-dependent effect of AgNPs on the kidney gene level based on toxicogenomic studies of kidneys obtained from rats exposed to AgNPs via inhalation for 12 weeks. When compared with the fresh air control, the silver nanoparticle-exposed kidneys included 104 genes with a more than 1.3-fold expression increase. For the male rat kidneys exposed to a low or high dose of silver nanoparticles, 96 genes exhibited expression changes, where six genes changed with both the low and high dose; four increased and two decreased. Meanwhile, for the female rat kidneys exposed to a low or high dose of silver nanoparticles, 66 genes exhibited expression changes, where 11 genes changed with both the low and high dose; nine increased and two decreased. Gender-dependent gene expression changes of more than 2-fold were linked to 163 genes, with 79 genes in the male kidneys and 84 genes in the female kidneys, plus gender-dependent gene expression changes of more than 5-fold were linked to 21 genes. However, no genes involved in apoptosis or the cell cycle were activated by the 12-week silver nanoparticle inhalation exposure. Overall, the male rat kidneys showed a higher expression of genes involved in xenobiotic metabolism, while the female rat kidneys showed a higher expression of genes involved in extracellular signaling.

Validation of the AOAC method for analyzing fatty acids in meat by-products for the Korean Food Composition Database.

The constituents of meat and meat by-product are susceptible to degradation processes, especially, the control of oxidative processes is critical. The main factors that influence their lipid oxidation are fat content and fatty acid composition. The aim of this study was to validate AOAC method 996.06 for analysis of fatty acid in meat by-products and to provide their accurate, precise, and reliable information in the Korean Food Composition Database. A total of 19 fatty acids were identified. The head, small intestine, stomach, and heart of pigs and the feet of chickens contained higher contents of total fatty acids, whereas the blood of cow had the lowest content. In particular, meat by-products other than the liver, blood, and stomach of cows and the stomach and small intestine of pigs contained higher contents of unsaturated fatty acids. Their main fatty acids were oleic acid, palmitic acid, linoleic acid, and stearic acid. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01223-8.