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1.
Curr Med Sci ; 43(5): 1013-1022, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37837571

ABSTRACT

OBJECTIVE: Compared to portal vein ligation (PVL), simultaneous bile duct and portal vein ligation (BPL) can significantly enhance hypertrophy of the intact liver. This study aimed to investigate whether BPL could improve survival after extended hepatectomy independently of an increased remnant liver. METHODS: We adopted rat models of 90% BPL or 90% PVL. To investigate the role of bile acids (BAs) the BA pools in the PVL and BPL groups were altered by the diet. Staged resection preserving 10% of the estimated liver weight was performed 3 days after BPL; PVL; or sham operation. Histology, canalicular network (CN) continuity; and hepatocyte polarity were evaluated. RESULTS: At 3 days after BPL; PVL; or sham operation when the volumetric difference of the intended liver remained insignificant, the survival rates after extended hepatectomy were 86.7%, 47%, and 23.3%, respectively (P<0.01). BPL induced faster restoration of canalicular integrity along with an intensive but transient BA overload. Staged hepatectomy after BPL shortened the duration of the bile CN disturbance and limited BA retention. Decreasing the BA pools in the rats that underwent BPL could compromise these effects, whereas increasing the BA pools of rats that underwent PVL could induce similar effects. The changes in CN restoration were associated with activation of LKB1. CONCLUSION: In addition to increasing the future remnant liver, BPL shortened the duration of the spatial disturbance of the CN and could significantly improve the tolerance of the hypertrophied liver to staged resection. BPL may be a safe and efficient future option for patients with an insufficient remnant liver.


Subject(s)
Hepatectomy , Portal Vein , Humans , Rats , Animals , Hepatectomy/adverse effects , Portal Vein/surgery , Bile Acids and Salts , Liver/pathology , Bile Ducts/surgery
2.
Plant Divers ; 45(3): 309-314, 2023 May.
Article in English | MEDLINE | ID: mdl-37397598

ABSTRACT

Independence among leaf economics, leaf hydraulics and leaf size confers plants great capability in adapting to heterogeneous environments. However, it remains unclear whether the independence of the leaf traits revealed across species still holds within species, especially under stressed conditions. Here, a suite of traits in these dimensions were measured in leaves and roots of a typical mangrove species, Ceriops tagal, which grows in habitats with a similar sunny and hot environment but different soil salinity in southern China. Compared with C. tagal under low soil salinity, C. tagal under high soil salinity had lower photosynthetic capacity, as indicated directly by a lower leaf nitrogen concentration and higher water use efficiency, and indirectly by a higher investment in defense function and thinner palisade tissue; had lower water transport capacity, as evidenced by thinner leaf minor veins and thinner root vessels; and also had much smaller single leaf area. Leaf economics, hydraulics and leaf size of the mangrove species appear to be coordinated as one trait dimension, which likely stemmed from co-variation of soil water and nutrient availability along the salinity gradient. The intraspecific leaf trait relationship under a stressful environment is insightful for our understanding of plant adaption to the multifarious environments.

3.
Stem Cell Res Ther ; 13(1): 109, 2022 03 21.
Article in English | MEDLINE | ID: mdl-35313972

ABSTRACT

BACKGROUND: Previous research has demonstrated that the spleen plays an important role in mesenchymal stem cell (MSC)-mediated alleviation of acute inflammation, as MSC infusion increases the spleen-derived anti-inflammatory cytokine interleukin 10 (IL-10) levels. However, studies on splenic involvement in MSC-induced protection against chronic inflammatory diseases are limited. Obesity is characterized by chronic low-grade inflammation, a key driver of insulin resistance. This study aims to evaluate the effects of MSCs on obesity-related insulin resistance and explore the underlying mechanism, particularly regarding splenic involvement. METHODS: We induced obesity in mice by feeding them high-fat diets for 20 weeks. Human umbilical cord-derived MSCs (UC-MSCs) were systemically infused into the obese mice once per week for 6 weeks. Systemic glucose metabolic homeostasis and insulin sensitivity in epididymal adipose tissue (EAT) were evaluated. Then, we conducted in vivo blockade of IL-10 during UC-MSC infusion by intraperitoneally administrating an IL-10-neutralizing antibody twice per week. We also investigated the therapeutic effects of UC-MSCs on obese mice after removal of the spleen by splenectomy. RESULTS: UC-MSC infusions improved systemic metabolic homeostasis and alleviated insulin resistance in EAT but elicited no change in weight. Despite rare engraftment of UC-MSCs in EAT, UC-MSC infusions attenuated insulin resistance in EAT by polarizing macrophages into the M2 phenotype, coupled with elevated serum IL-10 levels. In vivo blockade of IL-10 blunted the effects of UC-MSCs on obese mice. Furthermore, UC-MSCs overwhelmingly homed to the spleen, and the ability of UC-MSCs to elevate serum IL-10 levels and alleviate insulin resistance was impaired in the absence of the spleen. Further in vivo and in vitro studies revealed that UC-MSCs promoted the capacity of regulatory T cells (Treg cells) to produce IL-10 in the spleen. CONCLUSIONS: Our results demonstrated that UC-MSCs elevated serum IL-10 levels and subsequently promoted macrophage polarization, leading to alleviation of insulin resistance in EAT. The underlying mechanism was that UC-MSCs improved the capacity of Treg cells to produce IL-10 in the spleen. Our findings indicated that the spleen played a critical role in amplifying MSC-mediated immunomodulatory effects, which may contribute to maximizing MSC efficacy in clinical applications in the future.


Subject(s)
Insulin Resistance , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Animals , Diet, High-Fat/adverse effects , Humans , Mesenchymal Stem Cell Transplantation/methods , Mice , Mice, Obese , Spleen , Umbilical Cord
4.
Am Surg ; 88(6): 1172-1180, 2022 Jun.
Article in English | MEDLINE | ID: mdl-33522271

ABSTRACT

BACKGROUND: Neoadjuvant treatment (NT) has become standard in the management of borderline resectable pancreatic cancer (BR-PDAC), improving prognosis. The primary mechanism for this improvement remains unclear. METHODS: Clinicopathological data of patients with BR-PDAC who underwent resection between January 2008 and December 2018 at a single institution were retrospectively reviewed. Univariable and multivariate analyses were used to compare survival between patients who received NT vs. those who underwent upfront resection (UR). RESULTS: A total of 138 patients were included, 64 underwent UR and 74 NT. Neoadjuvant treatment resulted in higher margin-negative (R0) resection rate (68.9%) than UR (43.8%, P = .005). Neoadjuvant treatment was associated with improved overall survival (OS, P = .009) and progression-free survival (PFS, P = .027). R0 resection was also associated with improved OS (P < .001) and PFS (P < .001). On multivariable analysis, when adjusting for clinically relevant variables without considering R status, NT was an independent predictor for improved OS (P = .046) and PFS (P = .040). When additionally accounting for margin status, R0 was an independent predictor for improved OS (P < .001) and PFS (P < .001), while NT was not. Subgroup analysis, stratified by margin status, revealed that NT was not an independent predictor for OS or PFS for either subgroup. DISCUSSION: Neoadjuvant treatment is associated with improved OS and PFS in patients with BR-PDAC; however, this effect is outweighed by margin status. These results suggest that the primary benefit of NT was dependent on facilitating R0 resection. Upfront resection might remain a valid treatment option if R0 resection could be accurately predicted.


Subject(s)
Adenocarcinoma , Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Adenocarcinoma/drug therapy , Adenocarcinoma/surgery , Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/surgery , Humans , Neoadjuvant Therapy , Pancreatic Neoplasms/pathology , Prognosis , Retrospective Studies , Pancreatic Neoplasms
5.
Am Surg ; 88(12): 2899-2906, 2022 Dec.
Article in English | MEDLINE | ID: mdl-33861651

ABSTRACT

BACKGROUND: Many patients with borderline resectable/locally advanced pancreatic ductal adenocarcinoma (borderline resectable [BR]/locally advanced [LA] pancreatic ductal adenocarcinoma [PDAC]) undergoing resection will have positive resection margins (R1), which is associated with poor prognosis. It might be useful to preoperatively predict the margin (R) status. METHODS: Data from patients with BR/LA PDAC who underwent a pancreatectomy between 2008 and 2018 at Brigham and Women's Hospital were retrospectively reviewed. Logistic regression analysis was used to evaluate the association between R status and relevant preoperative factors. Significant predictors of R1 resection on univariate analysis (P < .1) were entered into a stepwise selection using the Akaike information criterion to define the final model. RESULTS: A total of 142 patients with BR/LA PDAC were included in the analysis, 60(42.3%) had R1 resections. In stepwise selection, the following factors were identified as positive predictors of an R1 resection: evidence of lymphadenopathy at diagnosis (OR = 2.06, 95% CI: 0.99-4.36, P = .056), the need for pancreaticoduodenectomy (OR = 3.81, 96% CI: 1.15-15.70, P = .040), extent of portal vein/superior mesenteric vein involvement at restaging (<180°, OR = 3.57, 95% CI: 1.00-17.00, P = .069, ≥180°, OR = 7,32, 95% CI: 1.75-39.87, P = .010), stable CA 19-9 serum levels (less than 50% decrease from diagnosis to restaging, OR = 2.27, 95% CI: 0.84-6.36 P = .107), and no preoperative FOLFIRINOX (OR = 2.17, 95% CI: 0.86-5.64, P = .103). The prognostic nomogram based on this model yielded a probability of achieving an R1 resection ranging from <5% (0 factors) to >70% (all 5 factors). CONCLUSIONS: Relevant preoperative clinicopathological characteristics accurately predict positive resection margins in patients with BR/LA PDAC before resection. With further development, this model might be used to preoperatively guide surgical decision-making in patients with BR/LA PDAC.


Subject(s)
Carcinoma, Pancreatic Ductal , Neoplasms, Second Primary , Pancreatic Neoplasms , Humans , Female , Pancreatic Neoplasms/surgery , Antineoplastic Combined Chemotherapy Protocols , Margins of Excision , Retrospective Studies , Neoadjuvant Therapy , Carcinoma, Pancreatic Ductal/surgery , Pancreatectomy , Neoplasms, Second Primary/surgery , Pancreatic Neoplasms
6.
J Surg Res ; 257: 605-615, 2021 01.
Article in English | MEDLINE | ID: mdl-32947122

ABSTRACT

BACKGROUND: The clinicopathologic factors associated with the survival of patients with pancreatic ductal adenocarcinoma (PDAC) during the different phases of neoadjuvant treatment (NT)-at diagnosis, restaging, or postoperatively-remain unclear. METHODS: Data of patients with PDAC who underwent pancreatic resection after NT between 2008 and 2018 were retrospectively collected. Clinicopathologic characteristics and outcomes were compared stratified by resection margin status. Three multivariable regression models (at diagnosis, restaging, and postoperatively) were constructed to assess the temporal impact of different prognostic factors on all-cause survival (ACS) and disease-free survival (DFS). RESULTS: All patients were diagnosed with a nonmetastatic PDAC and were appropriate candidates for NT according to the current National Comprehensive Cancer Network guidelines. From a total of 83 patients, 57 (68.7%) had a negative resection margin >1 mm (R0), whereas 26 patients (31.3%) had a positive resection margin (R1). At diagnosis, planned procedure (P = 0.017) and CA19-9 >100 U/mL (P = 0.047) were independent prognostic factors of decreased ACS. At restaging, planned procedure (P = 0.017), FOLFIRINOX (P = 0.026), and tumor size >30 mm (P = 0.030) were independent prognostic factors for increased and decreased ACS, respectively. Postoperatively, R0 was an independent prognostic factor for improved ACS (P = 0.005) and DFS (P = 0.002), whereas adjuvant therapy (P = 0.006) was associated with increased ACS. Lymph node involvement (P = 0.019) was associated with decreased DFS. CONCLUSIONS: At diagnosis, restaging, and postoperatively, different, relevant clinicopathologic factors significantly impact the survival of patients with nonmetastatic PDAC undergoing NT. An R0 resection remains the most important prognostic factor and therefore should be the primary goal of surgical treatment in the neoadjuvant setting.


Subject(s)
Carcinoma, Pancreatic Ductal/mortality , Neoadjuvant Therapy , Pancreatectomy , Pancreatic Neoplasms/mortality , Aged , Boston/epidemiology , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/therapy , Female , Humans , Male , Middle Aged , Pancreas/pathology , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/therapy , Prognosis , Proportional Hazards Models , Retrospective Studies
7.
J Surg Res ; 259: 253-260, 2021 03.
Article in English | MEDLINE | ID: mdl-33160635

ABSTRACT

BACKGROUND: Up to 50% of patients diagnosed with colorectal cancer develop metastases during the course of their disease. Surgical resection remains the only curative treatment option for colorectal liver metastases (CRLM), frequently in conjunction with neoadjuvant chemotherapy. This study sought to determine if the pathologic size of the largest CRLM impacted disease-free survival (DFS) and disease-specific survival (DSS) in the setting of neoadjuvant chemotherapy. METHODS: All patients diagnosed with CRLM who underwent neoadjuvant chemotherapy for liver resection at the Massachusetts General Hospital between 2004 and 2016 were reviewed. The median size of the largest liver lesion was used as the cutoff for grouped evaluation. RESULTS: A total of 214 patients were included. Median follow-up was 100.0 mo (interquartile range 68.9-133.8 mo). The median size of the largest lesion was 21 mm. Patients with lesions ≥21 mm exhibited significantly worse median DFS (12.5 mo versus 16.6 mo; P = 0.033) and median DSS (71.3 mo versus 103.5 mo; P = 0.038). CRLM lesions ≥21 mm were associated with poorer DFS on univariate analysis (hazard ratio (HR) = 1.42, 95% confidence interval (CI) 1.03-1.95 P = 0.033) and multivariable analysis (HR = 1.58, 95% CI 1.07-2.35, P = 0.023). CRLM lesions ≥21 mm were also independently associated with poorer DSS after liver resection on univariate analysis (HR = 1.51, 95% CI 1.02-2.24; P = 0.037) and multivariable analysis (HR = 1.98, 95% CI: 1.27-3.07; P = 0.002). CONCLUSIONS: The size of the largest CRLM is an important prognostic factor for both DFS and DSS after neoadjuvant therapy and serves as a useful indicator of tumor biology.


Subject(s)
Colorectal Neoplasms/pathology , Liver Neoplasms/secondary , Adult , Aged , Colorectal Neoplasms/mortality , Female , Hepatectomy , Humans , Liver Neoplasms/surgery , Male , Middle Aged , Neoadjuvant Therapy , Prognosis
8.
Dig Dis Sci ; 65(4): 1266-1275, 2020 04.
Article in English | MEDLINE | ID: mdl-31312995

ABSTRACT

BACKGROUND: There is lack of data for identifying optimal local therapy for the management of recurrent hepatocellular carcinoma (HCC) after hepatic resection. AIMS: A retrospective study was performed to compare the effectiveness of transarterial chemoembolization (TACE) plus radiofrequency ablation (RFA) with that of TACE alone for recurrent HCC. METHODS: From 2007 to 2013, patients with recurrent HCC ≤ 5 cm were treated with either TACE plus RFA (n = 96) or TACE (n = 63). Inverse probability of treatment weighting was used to make allowances for imbalances in treatment assignment. The disease-free survival (DFS) and overall survival (OS) were retrospectively analyzed. RESULTS: The TACE group had lower pretreatment Child-Pugh class (P = 0.025) and shorter pretreatment interval of recurrence (P = 0.028). The 1-, 3-, and 5-year DFS rates for the TACE-RFA group were 55.1%, 22.5%, and 9.7%, respectively, and 41.1%, 9.9%, and 4.9%, respectively, for the TACE group. The OS rates at 1, 3, and 5 years were 82.3%, 42.7%, and 16.5%, respectively, in the TACE-RFA group, and 75.9%, 30.7%, and 11.3%, respectively, in the TACE group. Cirrhosis was significantly associated with disease progression (hazard ratio [HR] 1.53; 95% CI 1.09-2.14; P = 0.014). CONCLUSIONS: In patients with recurrent HCC ≤ 5 cm, TACE-RFA shows better DFS than TACE alone as a first-line local therapy.


Subject(s)
Carcinoma, Hepatocellular/therapy , Catheter Ablation/trends , Chemoembolization, Therapeutic/trends , Liver Neoplasms/therapy , Neoplasm Recurrence, Local/therapy , Adult , Carcinoma, Hepatocellular/diagnosis , Catheter Ablation/methods , Chemoembolization, Therapeutic/methods , Combined Modality Therapy/methods , Female , Follow-Up Studies , Humans , Infusions, Intra-Arterial/methods , Liver Neoplasms/diagnosis , Male , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Retrospective Studies , Time Factors , Treatment Outcome
10.
BMC Ecol ; 19(1): 41, 2019 09 18.
Article in English | MEDLINE | ID: mdl-31533695

ABSTRACT

BACKGROUND: Understanding how traditional agriculture systems have been maintained would help design sustainable agriculture. In this study, we examined how farmers have used two types of local trees (Torreya grandis) for stable yield and maintaining genetic diversity in the "globally important agricultural heritage torreya tree system". The two type of torreya trees are grafted torreya (GT) tree and non-grafted-torreya (NGT) tree. The GT tree has only female and was used to produced seed yields. The NGT tree has both male and female and was used to support GT tree by providing pollens and rootstocks. We first tested the ratio of GT tree to NGT tree, their age groups, ratio of female trees (including GT and NGT trees) to male, and the flowering period of GT and NGT trees. We then tested seed yields and genetic diversity of GT and NGT trees. We further tested gene flow among NGT trees, and the relationship of gene flow with exchange rates of pollens and seeds. RESULTS: GT and NGT trees (male and female) were planted in a mosaic pattern with a ratio of 4:1 (GT:NGT). In this planting pattern, one NGT male trees provided pollen for 20 female trees of GT and NGT. The trees were classified into four age groups (I = 100-400 years old; II = 400-700 years old; III = 700-1000 years old; and IV = 1000-1300 years old) based on basal diameter. The entire flowering period was longer for NGT trees than for GT trees that ensured GT trees (which lack of males) being exposed to pollens. GT tree had high and stable seed yield that increased with age groups. High genetic diversity has been maintained in both rootstocks of the GT trees and NGT trees. There was a strong gene flow among NGT trees, which positive correlated with the exchange rates of pollens and seeds. CONCLUSIONS: Our results suggest that farmers obtain stable seed yields, and maintain high genetic diversity by ingeniously using the local GT tree as yield producer and NGT tree as supporter. These GT and NGT trees together ensure sustainable torreya production.


Subject(s)
Taxaceae , Trees , Agriculture , Female , Gene Flow , Genetic Variation , Male , Seeds
11.
EMBO J ; 38(17): e101110, 2019 09 02.
Article in English | MEDLINE | ID: mdl-31334575

ABSTRACT

Hepatocellular carcinoma (HCC) is the most prevalent liver cancer, characterized by a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may well contribute to both of these pathological properties, but the mechanism underlying their self-renewal maintenance is poorly understood. Here, we identified a long noncoding RNA (lncRNA) termed HAND2-AS1 that is highly expressed in liver CSCs. Human HAND2-AS1 and its mouse ortholog lncHand2 display a high level of conservation. HAND2-AS1 is required for the self-renewal maintenance of liver CSCs to initiate HCC development. Mechanistically, HAND2-AS1 recruits the INO80 chromatin-remodeling complex to the promoter of BMPR1A, thereby inducing its expression and leading to the activation of BMP signaling. Importantly, interfering with expression of HAND2-AS1 by antisense oligonucleotides (ASOs) and BMPR1A by siRNAs has synergistic anti-tumorigenic effects on humanized HCC models. Moreover, knockout of lncHand2 or Bmpr1a in mouse hepatocytes impairs BMP signaling and suppresses the initiation of liver cancer. Our findings reveal that HAND2-AS1 promotes the self-renewal of liver CSCs and drives liver oncogenesis, offering a potential new target for HCC therapy.


Subject(s)
Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , Neoplastic Stem Cells/chemistry , RNA, Long Noncoding/genetics , Signal Transduction , ATPases Associated with Diverse Cellular Activities/genetics , Animals , Bone Morphogenetic Protein Receptors, Type I/genetics , Bone Morphogenetic Proteins/metabolism , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Self Renewal , DNA-Binding Proteins/genetics , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Mice , Neoplasm Transplantation , Neoplastic Stem Cells/pathology , Up-Regulation
12.
Nat Immunol ; 20(2): 183-194, 2019 02.
Article in English | MEDLINE | ID: mdl-30643264

ABSTRACT

Intestinal stem cells (ISCs) are maintained by stemness signaling for precise modulation of self-renewal and differentiation under homeostasis. However, the way in which intestinal immune cells regulate the self-renewal of ISCs remains elusive. Here we found that mouse and human Lgr5+ ISCs showed high expression of the immune cell-associated circular RNA circPan3 (originating from the Pan3 gene transcript). Deletion of circPan3 in Lgr5+ ISCs impaired their self-renewal capacity and the regeneration of gut epithelium in a manner dependent on immune cells. circPan3 bound mRNA encoding the cytokine IL-13 receptor subunit IL-13Rα1 (Il13ra1) in ISCs to increase its stability, which led to the expression of IL-13Rα1 in ISCs. IL-13 produced by group 2 innate lymphoid cells in the crypt niche engaged IL-13Rα1 on crypt ISCs and activated signaling mediated by IL-13‒IL-13R, which in turn initiated expression of the transcription factor Foxp1. Foxp1 is associated with ß-catenin in rendering its nuclear translocation, which caused activation of the ß-catenin pathway and the maintenance of Lgr5+ ISCs.


Subject(s)
Cell Self Renewal/immunology , Interleukin-13/metabolism , Intestinal Mucosa/immunology , RNA/metabolism , Stem Cells/physiology , Animals , Carrier Proteins/genetics , Cell Differentiation/immunology , Cell Self Renewal/genetics , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/immunology , Dextran Sulfate/toxicity , Disease Models, Animal , Female , Humans , Interleukin-13/immunology , Interleukin-13 Receptor alpha1 Subunit/genetics , Interleukin-13 Receptor alpha1 Subunit/immunology , Interleukin-13 Receptor alpha1 Subunit/metabolism , Intestinal Mucosa/cytology , Intestinal Mucosa/metabolism , Lymphocytes/immunology , Lymphocytes/metabolism , Mice , Mice, Inbred C57BL , Mice, Inbred ICR , Mice, Knockout , RNA/genetics , RNA/immunology , RNA, Circular , RNA, Messenger/metabolism , Receptors, G-Protein-Coupled/metabolism , Regeneration/genetics , Regeneration/immunology , Signal Transduction/genetics , Signal Transduction/immunology , beta Catenin/immunology , beta Catenin/metabolism
13.
Nat Cell Biol ; 20(10): 1134-1144, 2018 10.
Article in English | MEDLINE | ID: mdl-30224759

ABSTRACT

The intestinal epithelium harbours remarkable self-renewal capacity that is driven by Lgr5+ intestinal stem cells (ISCs) at the crypt base. However, the molecular mechanism controlling Lgr5+ ISC stemness is incompletely understood. We show that a Gata6 long noncoding RNA (lncGata6) is highly expressed in ISCs. LncGata6 knockout or conditional knockout in ISCs impairs the stemness of ISCs and epithelial regeneration. Mechanistically, lncGata6 recruits the NURF complex onto the Ehf promoter to induce its transcription, which promotes the expression of Lgr4/5 to enhance Wnt signalling activation. Moreover, the human orthologue lncGATA6 is highly expressed in the cancer stem cells of colorectal cancer and promotes tumour initiation and progression. Antisense oligonucleotides against lncGATA6 exhibit strong therapeutic efficacy on colorectal cancer. Thus, targeting lncGATA6 will have potential clinical applications in colorectal cancer treatment as an ideal therapeutic target.


Subject(s)
Cell Transformation, Neoplastic/genetics , Intestinal Mucosa/metabolism , RNA, Long Noncoding/genetics , Stem Cells/metabolism , Animals , Cell Transformation, Neoplastic/metabolism , Cells, Cultured , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Gene Expression Profiling/methods , Humans , Intestinal Mucosa/cytology , Mice, Inbred C57BL , Mice, Inbred NOD , Mice, Knockout , Mice, SCID , Mice, Transgenic , RNA, Long Noncoding/metabolism , Transplantation, Heterologous , Tumor Cells, Cultured
14.
Proc Natl Acad Sci U S A ; 115(3): E546-E554, 2018 01 16.
Article in English | MEDLINE | ID: mdl-29295926

ABSTRACT

We examined how traditional farmers preserve the genetic diversity of a local common carp (Cyprinus carpio), which is locally referred to as "paddy field carp" (PF-carp), in a "globally important agricultural heritage system" (GIAHS), i.e., the 1,200-y-old rice-fish coculture system in Zhejiang Province, China. Our molecular and morphological analysis showed that the PF-carp has changed into a distinct local population with higher genetic diversity and diverse color types. Within this GIAHS region, PF-carps exist as a continuous metapopulation, although three genetic groups could be identified by microsatellite markers. Thousands of small farmer households interdependently obtained fry and parental carps for their own rice-fish production, resulting in a high gene flow and large numbers of parent carps distributing in a mosaic pattern in the region. Landscape genetic analysis indicated that farmers' connectivity was one of the major factors that shaped this genetic pattern. Population viability analysis further revealed that the numbers of these interconnected small farmer households and their connection intensity affect the carps' inherent genetic diversity. The practice of mixed culturing of carps with diverse color types helped to preserve a wide range of genetic resources in the paddy field. This widespread traditional practice increases fish yield and resource use, which, in return, encourages famers to continue their practice of selecting and conserving diverse color types of PF-carp. Our results suggested that traditional farmers secure the genetic diversity of PF-carp and its viability over generations in this region through interdependently incubating and mixed-culturing practices within the rice-fish system.


Subject(s)
Agriculture/methods , Carps/genetics , Genetic Variation , Animals , China , Microsatellite Repeats , Oryza/physiology , Phylogeny
15.
Jpn J Infect Dis ; 70(1): 32-37, 2017 Jan 24.
Article in English | MEDLINE | ID: mdl-27169945

ABSTRACT

In order to evaluate the clinical characteristics of confirmed Ebola Virus Disease (EVD) patients admitted to the China Ebola Treatment Unit (China ETU) between January 2015 and March 2015, we retrospectively analyzed clinical symptoms, treatment, and epidemiologic features of 5 patients with confirmed EVD, and reviewed the relevant medical literature. Of these, 3 patients survived, and 2 died. The time interval from the onset of symptoms to the negative PCR test for Ebola virus in the 3 survivors was 14-18 days. All survivors reported direct contact with confirmed EVD patients up to 21 days prior to admission. All patients developed a fever, fatigue, and anorexia. Fever was generally the first symptom to develop, followed by a gastrointestinal phase characterized by vomiting/nausea (3 cases, 60%), diarrhea (3 cases), and abdominal pain (4 cases, 80%). Three patients (60%) reported joint pain, muscle pain, and conjunctival hemorrhage, respectively, and 2 patients (40%) developed a headache. We concluded that strict isolation and interruption of the route of transmission were required for suspected or confirmed EVD patients. The main treatment strategies were supportive care, maintenance of blood volume and electrolyte balance, and the prevention of complications.


Subject(s)
Fluid Therapy/methods , Hemorrhagic Fever, Ebola/pathology , Hemorrhagic Fever, Ebola/therapy , Adult , Female , Hemorrhagic Fever, Ebola/epidemiology , Humans , Liberia/epidemiology , Male , Middle Aged , Polymerase Chain Reaction , RNA, Viral/analysis , RNA, Viral/genetics , Retrospective Studies , Survival , Time Factors
16.
J Diabetes Investig ; 8(1): 44-55, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27184687

ABSTRACT

AIMS/INTRODUCTION: Moderate elevation of glucose level has been shown to effectively promote ß-cell replication in various models in vitro and in normal rodents. Here, we aimed to test the effect of moderately elevated glucose on ß-cell mass expansion and islet function recovery in diabetic animal models. MATERIALS AND METHODS: A single high dose of streptozotocin was given to induce insulin-deficient diabetes in adult male Sprague-Dawley rats. Then, 48 h after streptozotocin injection, newly diabetic rats were randomly divided into three groups: (i) no treatment to maintain hyperglycemia; (ii) daily exogenous long-acting human insulin analog injection that maintained mild hyperglycemia (15 mmol/L < blood glucose < 18 mmol/L); (iii) daily exogenous long-acting human insulin analog injection to restore normoglycemia (blood glucose <8 mmol/L) as a control. Islet function, ß-cell regeneration and ß-cell replication were monitored during the entire analysis period. RESULTS: A single high dose of streptozotocin induced massive loss of ß-cells, resulting in irreversible hyperglycemia. Mild hyperglycemia markedly promoted ß-cell proliferation, leading to robust ß-cell regeneration. Importantly, rats that maintained mild hyperglycemia showed nearly normal glucose-stimulated insulin secretion, glucose disposal and random blood glucose levels, suggesting almost full restoration of the islet function. Normalization of blood glucose levels profoundly blunted ß-cell replication, regeneration and islet function recovery observed in mild hyperglycemia. CONCLUSIONS: Our research provides a feasible approach to stimulate in situ ß-cell regeneration in diabetic rats, offering new perspectives for diabetes therapy.


Subject(s)
Diabetes Mellitus, Experimental/physiopathology , Hyperglycemia/physiopathology , Insulin-Secreting Cells/physiology , Animals , Apoptosis , Blood Glucose/metabolism , Cell Proliferation , Cells, Cultured , Diabetes Mellitus, Experimental/metabolism , Glucagon-Secreting Cells/metabolism , Glucagon-Secreting Cells/physiology , Humans , Hyperglycemia/metabolism , Insulin/administration & dosage , Insulin/analogs & derivatives , Insulin/blood , Insulin-Secreting Cells/metabolism , Male , Rats , Rats, Sprague-Dawley , Streptozocin
17.
Ying Yong Sheng Tai Xue Bao ; 27(2): 601-10, 2016 Feb.
Article in Chinese | MEDLINE | ID: mdl-27396136

ABSTRACT

Isotopic enrichment factor (Δ, the difference between the δ value of food and a consumer tissue) is an important parameter in using stable isotope analysis (SIA) to reconstruct diets, characterize trophic relationships, elucidate patterns of resource allocation, and construct food webs. Isotopic enrichment factor has been considered as a constancy value across a broad range of animals. However, recent studies showed that the isotopic enrichment factor differed among various types of animals although the magnitude of variation was not clear. Here, we conducted a meta-analysis to synthesize and compare Δ13C and Δ15N among four types of aquatic animals (teleosts, crustaceans, reptiles and molluscs). We searched for papers published before 2014 on Web of Science and CNKI using the key words "stable isotope or isotopic fractionation or fractionation factor or isotopic enrichment or trophic enrichment". Forty-two publications that contain 140 studies on Δ13C and 159 studies on Δ15N were obtained. We conducted three parallel meta-analyses by using three types of weights (the reciprocal of variance as weights, the sample size as weights, and equal weights). The results showed that no significant difference in Δ13C among different animal types (teleosts 1.0 per thousand, crustaceans 1.3 per thousand, reptiles 0.5 per thousand, and molluscs 1.5 per thousand), while Δ15N values were significantly different (teleosts 2.4 per thousand, crustaceans 3.6 per thousand, reptiles 1.0 per thousand and molluscs 2.5 per thousand). Our results suggested that the overall mean of Δ13C could be used as a general enrichment factor, but Δ15N should be chosen according to the type of aquatic animals in using SIA to analyze trophic relationships, patterns of resource allocation and food webs.


Subject(s)
Carbon Isotopes/analysis , Food Chain , Nitrogen Isotopes/analysis , Animals , Crustacea , Diet , Fishes , Mollusca , Reptiles
18.
Sci Rep ; 6: 28728, 2016 06 28.
Article in English | MEDLINE | ID: mdl-27349875

ABSTRACT

Because rice feeds half of the world's population, a secure global food supply depends on sustainable rice production. Here we test whether the co-cultivation of rice and fish into one "rice-fish system" (RFS; fish refers to aquatic animals in this article) could help sustain rice production. We examined intensive and traditional RFSs that have been widely practiced in China. We found that rice yields did not decrease when fish yield was below a threshold value in each intensive RFS. Below the thresholds, moreover, fish yields in intensive RFSs can be substantially higher than those in traditional RFS without reducing rice yield. Relative to rice monoculture, the use of fertilizer-nitrogen and pesticides decreased, and the farmers' net income increased in RFSs. The results suggest that RFSs can help sustain rice production, and suggest that development of co-culture technologies (i.e. proper field configuration for fish and rice) is necessary to achieve the sustainability.


Subject(s)
Carps/growth & development , Crop Production/methods , Oryza/growth & development , Animals , China
19.
J Surg Res ; 195(2): 454-64, 2015 May 15.
Article in English | MEDLINE | ID: mdl-25770738

ABSTRACT

BACKGROUND: Clinically, hepatectomy is a clean procedure performed without routine antimicrobial prophylaxis, regardless of the extent of liver loss. Translocation of endotoxin has been recognized as a fatal complication leading to liver failure. After extended hepatectomy, the portal hypertension, mucosal damage, intrahepatic bile acid retention, inhibited enterokinesia, and so forth are likely to contribute to enhanced endotoxin absorption. The effect of selective bowel decontamination (SBD) on the prognosis of hepatectomy were investigated. METHODS: We adopted rat models of partial hepatectomy (70%, PHx) and subtotal hepatectomy (90%, SHx), gentamicin or saline of the same amount was administrated preoperatively. Liver damage makers, portal and systemic lipopolysaccharide, mucosal damage, signaling pathways, liver regeneration, and bile canalicular networks reconstruction were investigated. RESULTS: We found that SHx but not PHx resulted in significantly enhanced portal and systemic endotoxin. Inhibition of gastrointestinal gram-negative bacteria by gentamicin significantly reduced lipopolysaccharide levels and improved survival after SHx (56% with gentamicin, 24% with saline, P < 0.05). We also found SBD with gentamicin protected intestinal mucosa barrier, alleviated liver parenchymal damage, and promoted liver regeneration and bile canalicular networks reconstruction after extended liver resection. CONCLUSIONS: We conclude that SBD is beneficial and necessary for extended hepatectomy.


Subject(s)
Decontamination , Gastrointestinal Tract/microbiology , Hepatectomy/mortality , Animals , Epidermal Growth Factor/physiology , Gentamicins/pharmacology , Intestinal Mucosa/metabolism , Lipopolysaccharides/metabolism , Liver Regeneration , Male , Rats , Rats, Sprague-Dawley
20.
Sci Rep ; 5: 8455, 2015 Feb 13.
Article in English | MEDLINE | ID: mdl-25678050

ABSTRACT

Portal vein ligation (PVL) induces atrophy/hypertrophy complex (AHC). We hypothesised that simultaneous bile duct and portal vein ligation (BPL) might induce proper bile acid (BA) retention to enhance AHC by activating BA-mediated FXR signalling in the intact liver and promoting apoptosis in the ligated liver. We established rat models of 90% BPL and 90% PVL and found that BPL was well-tolerated and significantly accelerated AHC. The enhanced BA retention in the intact liver promoted hepatocyte proliferation by promoting the activation of FXR signalling, while that in the ligated liver intensified caspase3-mediated apoptosis. Decreasing the BA pools in the rats that underwent BPL could compromise these effects, whereas increasing the bile acid pools of rats that underwent PVL could induce similar effects. Second-stage resection of posterior-caudate-lobe-spearing hepatectomy was performed 5 days after BPL (B-Hx), PVL (V-Hx) or sham (S-SHx), as well as whole-caudate-lobe-spearing hepatectomy 5 days after sham (S-Hx). The B-Hx group had the most favourable survival rate (93.3%, the S-SHx group 0%, the S-Hx group 26.7%, the V-Hx group 56.7%, P < 0.01) and the most sustained regeneration. We conclude that BPL is a safe and effective method, and the acceleration of AHC was bile acid-dependent.


Subject(s)
Bile Acids and Salts/metabolism , Bile Ducts/surgery , Liver/pathology , Portal Vein/surgery , Animals , Apoptosis/drug effects , Atrophy , Caspase 3/metabolism , Cell Proliferation/drug effects , Fragile X Mental Retardation Protein/metabolism , Hepatectomy , Hepatocytes/cytology , Hepatocytes/metabolism , Hypertrophy , Liver Regeneration/physiology , Male , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Taurocholic Acid/pharmacology
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