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1.
Ren Fail ; 46(1): 2325644, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38445391

ABSTRACT

OBJECTIVE: In China, most of the patients who underwent kidney transplants have unknown causes of end-stage renal disease (uESRD). However, little is known regarding the incidence of graft glomerulonephritis (GN) and graft survival in kidney transplant recipients (KTRs) with uESRD. METHODS: In this retrospective cohort study, 473 of the 565 KTRs who underwent kidney transplantation (KTx) from 2015 to 2020 were included. We mainly observed the occurrence of graft GN between uESRD group and definitively diagnosed GN group, and repeatedly compared after propensity score matching (PSM). RESULTS: The median follow-up was 50 months in 473 KTRs, and about 75% of KTRs of native kidney disease of unknown etiology. The total cumulative incidence of graft GN was 17%, and no difference was observed between the definitively diagnosed GN group and the uESRD group (p = 0.76). Further, PSM analysis also showed no difference in the incidence of graft GN between the 2 groups. Multivariable analysis disclosed males (p = 0.001), younger age (p = 0.03), and anti-endothelial cell anti-body (AECA) positive pre-KTx (p = 0.001) were independent risk factors for graft GN. CONCLUSIONS: The incidence of graft GN was similar between uESRD and definitively diagnosed GN group. The allograft survival was also similar between two groups.


Subject(s)
Glomerulonephritis , Kidney Failure, Chronic , Male , Humans , Incidence , Retrospective Studies , Glomerulonephritis/complications , Glomerulonephritis/epidemiology , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/surgery , China/epidemiology
2.
World J Surg Oncol ; 21(1): 28, 2023 Jan 31.
Article in English | MEDLINE | ID: mdl-36721235

ABSTRACT

BACKGROUND AND OBJECTIVES: In patients with colorectal cancer and clinically suspected para-aortic lymph node metastasis, the survival benefit of para-aortic lymphadenectomy is unknown. We conducted a meta-analysis and systematic review to investigate it. METHODS: PubMed, Web of Science, and EMBASE were searched until January 2000 to April 2022 to identify studies reporting overall survivals, complication rates, and hazard ratios of prognostic factors in patients with colorectal cancer undergoing para-aortic lymphadenectomy, and those data were pooled. RESULTS: Twenty retrospective studies (1021 patients undergoing para-aortic lymphadenectomy) met the inclusion criteria. Meta-analysis indicates that participants undergoing para-aortic lymphadenectomy were associated with 5-year survival benefit, compared to those not receiving para-aortic lymphadenectomy (odds ratio = 3.73, 95% confidence interval: 2.05-6.78), but there was no significant difference in complication rate (odds ratio = 0.97, 95% confidence interval: 0.46-2.08). Further analysis of para-aortic lymphadenectomy group showed that 5-year survival of the positive group with pathologically para-aortic lymph node metastasis was lower than that of the negative group (odds ratio = 0.19, 95% confidence interval: 0.11-0.31). Moreover, complete resection (odds ratio = 5.26, 95% confidence interval: 2.02-13.69), para-aortic lymph node metastasis (≤4) (hazard ratio = 1.88, 95% confidence interval: 0.97-3.62), and medium-high differentiation (hazard ratio = 2.98, 95% confidence interval: 1.48-5.99) were protective factors for survival. Preoperative extra-retroperitoneal metastasis was associated with poorer relapse-free survival (hazard ratio = 1.85, 95% confidence interval: 1.10-3.10). CONCLUSION: Para-aortic lymphadenectomy had promising clinical efficacy in prolonging survival rather than complication rate in patients with colorectal cancer and clinically diagnostic para-aortic lymph node metastasis. Further prospective studies should be performed. TRIAL REGISTRATION: PROSPERO: CRD42022379276.


Subject(s)
Colorectal Neoplasms , Lymph Node Excision , Humans , Colorectal Neoplasms/surgery , Lymphatic Metastasis , Prospective Studies , Retrospective Studies
3.
Cell Tissue Bank ; 24(2): 417-434, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36434165

ABSTRACT

Bone grafts are widely used to successfully restore structure and function to patients with a broad range of musculoskeletal ailments and bone defects. Autogenous bone grafts are historically preferred because they theoretically contain the three essential components of bone healing (ie, osteoconductivity, osteoinductivity, and osteogenicity), but they have inherent limitations. Allograft bone derived from deceased human donors is one alternative that is also capable of providing both an osteoconductive scaffold and osteoinductive potential but, until recently, lacked the osteogenic component of bone healing. Relatively new, cellular bone allografts (CBAs) were designed to address this need by preserving viable cells. Although most commercially-available CBAs feature mesenchymal stem cells (MSCs), osteogenic differentiation is time-consuming and complex. A more advanced graft, a viable bone allograft (VBA), was thus developed to preserve lineage-committed bone-forming cells, which may be more suitable than MSCs to promote bone fusion. The purpose of this paper was to present the results of preclinical research characterizing VBA. Through a comprehensive series of in vitro and in vivo assays, the present results demonstrate that VBA in its final form is capable of providing all three essential bone remodeling properties and contains viable lineage-committed bone-forming cells, which do not elicit an immune response. The results are discussed in the context of clinical evidence published to date that further supports VBA as a potential alternative to autograft without the associated drawbacks.


Subject(s)
Allografts , Bone Transplantation , Bone Transplantation/economics , Bone Transplantation/methods , Humans , Transplantation, Autologous , Bone Matrix/chemistry , Osteocytes/cytology , Cell Proliferation , Calcium/metabolism , Bone Marrow Cells/metabolism , Allografts/cytology , Allografts/immunology , Histocompatibility
4.
Int J Environ Health Res ; 33(2): 219-229, 2023 Feb.
Article in English | MEDLINE | ID: mdl-34915782

ABSTRACT

This study explored whether using a coal or biomass stove for cooking was associated with a greater risk of red blood cell (RBC) folate insufficiency among pregnant women compared to using clean energy. A researcher-designed questionnaire was used to collect information on exposure-related factors and confounding factors. RBC folate concentrations were examined by microbiological assay. Binary logistic regression analysis was used to identify factors related to RBC folate insufficiency. The use of coal or firewood for cooking was associated with an increased risk of RBC folate insufficiency (<906 nmol/L) compared to gas. In subgroup analyses, associations between the use of polluting cooking fuels and folate insufficiency were positive for both urban and rural residents and statistically significant for rural women. Efforts to promote the use of clean energy and proper ventilation, especially in rural areas, are recommended to improve the health of pregnant women and their offspring.


Subject(s)
Air Pollution, Indoor , Pregnant Women , Humans , Female , Pregnancy , Folic Acid/analysis , Air Pollution, Indoor/adverse effects , Air Pollution, Indoor/analysis , Coal/toxicity , Cooking , China/epidemiology
5.
Stroke ; 52(4): 1339-1346, 2021 04.
Article in English | MEDLINE | ID: mdl-33657859

ABSTRACT

BACKGROUND AND PURPOSE: We investigated the prevalence, awareness, and control of vascular risk factors (VRFs) and the use of antithrombotic and statin agents in HCHS (Hispanic Community Health Study)/SOL (Study of Latinos) participants with self-reported history of stroke or transient ischemic attack. METHODS: Sociodemographic characteristics, medications, and prevalence of different VRFs were recorded. VRF diagnoses and goals were based on the recommendations of professional organizations. Factors associated with optimal VRF control and use of antithrombotic and statin agents were investigated using multivariate logistic regression. RESULTS: The analysis included 404 participants (39% men). The prevalences of hypertension, dyslipidemia, and diabetes were 59%, 65%, and 39%, respectively. Among those who met the diagnostic criteria for these diagnoses, the frequencies of awareness were 90%, 75%, and 83%, respectively. In participants who were aware of their VRFs, the prevalences of controlled hypertension, dyslipidemia, and diabetes were 46%, 32%, and 54%. Approximately 46% of the participants were on antithrombotics, 39% on statins, and 26% on both. Only 38% of those with atrial fibrillation received anticoagulation. In multivariate analyses adjusted for baseline sociodemographic characteristics, older age was associated with uncontrolled hypertension and diabetes. Residing in the United States for ≥10 years and born in the United States were associated with uncontrolled diabetes, female sex with uncontrolled dyslipidemia, and lack of health insurance with decreased use of statins and hyperlipidemia. CONCLUSIONS: Hispanic/Latino adults in the United States have high prevalence and awareness of VRFs but low adherence to secondary stroke prevention strategies. Older adults, women, and uninsured people are vulnerable groups that may benefit from targeted interventions. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02060344.


Subject(s)
Cardiovascular Diseases/epidemiology , Fibrinolytic Agents/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Secondary Prevention , Stroke/prevention & control , Aged , Cardiovascular Diseases/complications , Cohort Studies , Female , Hispanic or Latino , Humans , Male , Medication Adherence/statistics & numerical data , Middle Aged , Prevalence , Risk Factors , Secondary Prevention/methods , Secondary Prevention/statistics & numerical data , Stroke/etiology , United States
6.
Surg Endosc ; 35(3): 1126-1137, 2021 03.
Article in English | MEDLINE | ID: mdl-32140860

ABSTRACT

BACKGROUND AND AIMS: Previous studies have suggested that aggressive hydration with lactated ringer solution are one of the protective factors in preventing post endoscopic retrograde cholangiopancreatography (post-ERCP). We conducted a systematic review and meta-analysis to examine the efficacy aggressive hydration with lactated Ringer solution in preventing PEP. METHODS: All published and unpublished articles on aggressive hydration with lactated ringer solution in those underwent ERCP procedure for any reasons were screened for eligibility. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. This paper doesn't need the IRB approval. RESULTS: Seven RCTs met the inclusion criteria. Meta-analysis indicates that aggressive hydration with lactated Ringer solution were associated with lower PEP rate.[odds ratio (OR) 0.29; 95% confidence interval (CI) 0.18-0.48]; lower incidence of hyperamylasemia (OR 0.49; 95% CI 0.35, 0.69) and lower risk of pain (OR 0.28; 95% CI 0.10-0.81). The association between aggressive hydration with lactated Ringer solution and incidence of moderate severity PEP were unclear (OR 0.57; 95% CI 0.22, 1.45). Sensitivity analyses also showed that omitting 1 study from analysis of PEP rate could reduce the heterogeneity but did not change the conclusion of this meta-analysis. A cumulating meta-analysis was performed statistically which showed a stable result of overall incidence of PEP. CONCLUSIONS: Aggressive hydration with lactated Ringer solution was a protective factor in reducing the overall incidence of PEP, hyperamylasemia and risk of abdominal pain.


Subject(s)
Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Pancreatitis/etiology , Pancreatitis/prevention & control , Ringer's Lactate/therapeutic use , Abdominal Pain/etiology , Abdominal Pain/prevention & control , Humans , Hyperamylasemia/prevention & control , Incidence , Odds Ratio , Pancreatitis/epidemiology , Protective Agents/therapeutic use , Randomized Controlled Trials as Topic
7.
Mol Cell Biochem ; 475(1-2): 151-159, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32767228

ABSTRACT

More than 50% of colorectal cancer (CRC) deaths are attributed to metastasis, and the liver is the most common distant metastatic site of CRC. The molecular mechanisms underlying CRC liver metastasis are very complicated and remain largely unknown. Accumulated evidence has shown that non-coding RNAs (NcRNAs) play critical roles in tumor development and progression. Here we reviewed the roles and underlying mechanisms of NcRNAs in CRC liver metastasis.


Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Liver Neoplasms/genetics , Liver Neoplasms/secondary , RNA, Circular/genetics , RNA, Untranslated/genetics , Biomarkers, Tumor/genetics , Disease Progression , Humans , MicroRNAs/genetics
8.
J Cell Biochem ; 120(7): 10956-10963, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30945338

ABSTRACT

Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs that form covalently closed continuous loops without 3' end poly (A) tails and 5' end caps. circRNAs are more conservative and stable than linear RNA. circRNAs can specifically bind to microRNAs as competing endogenous RNA, thereby directly or indirectly regulating the expression of related genes. circRNAs have been implicated in several cancers including gastrointestinal (GI) cancers. Some circRNAs have the potential to become biological biomarkers and therapeutic targets of GI cancers. However, the multiple functional roles of circRNAs in GI cancers remain largely unclear.

9.
Cancer Sci ; 110(3): 997-1011, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30618098

ABSTRACT

The catalytic subunit p110δ of phosphoinositide 3-kinase (PI3K) encoded by PIK3CD has been implicated in some human solid tumors. However, its roles in colorectal cancer (CRC) remain largely unknown. Here we found that PIK3CD was overexpressed in colon cancer tissues and CRC cell lines and was an independent predictor for overall survival (OS) of patients with colon cancer. The ectopic overexpression of PIK3CD significantly promoted CRC cell growth, migration and invasion in vitro and tumor growth in vivo. In contrast, inhibition of PIK3CD by specific small-interfering RNA or idelalisib dramatically suppressed CRC cell growth, migration and invasion in vitro and tumor growth in vivo. Moreover, PIK3CD overexpression increased AKT activity, nuclear translocation of ß-catenin and T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activity and decreased glycogen synthase kinase 3ß (GSK-3ß) activity, whereas PIK3CD inhibition exhibited the opposite effects. Furthermore, PIK3CD-mediated cell growth, migration and invasion were reversed by blockade of AKT signaling or depletion of ß-catenin. In addition, PIK3CD expression in colon cancer tissues positively correlated with ß-catenin abnormal expression, which was an independent predictor for OS of colon cancer patients. Taken together, our findings demonstrate that PIK3CD is an independent prognostic factor in CRC and that PIK3CD induces CRC cell growth, migration and invasion by activating AKT/GSK-3ß/ß-catenin signaling, suggesting that PIK3CD might be a novel prognostic biomarker and a potential therapeutic target for CRC.


Subject(s)
Cell Proliferation/genetics , Class I Phosphatidylinositol 3-Kinases/genetics , Colorectal Neoplasms/genetics , Glycogen Synthase Kinase 3 beta/genetics , Neoplasm Invasiveness/genetics , Proto-Oncogene Proteins c-akt/genetics , Signal Transduction/genetics , Cell Line, Tumor , Cell Movement/genetics , Colorectal Neoplasms/pathology , Gene Expression Regulation, Neoplastic/genetics , HCT116 Cells , HT29 Cells , Humans , Neoplasm Invasiveness/pathology , RNA, Small Interfering/genetics , beta Catenin/genetics
10.
Future Oncol ; 14(13): 1307-1316, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29741114

ABSTRACT

Accumulated evidence has shown that colonoscopy may not be a perfect tool in screening and reducing the incidence of the colorectal cancer (CRC), because interval CRC (I-CRC), a specific subgroup of CRCs, has been challenging the traditional detection technology in recent years. I-CRC is accounting for an increasing proportion in CRCs. However, the effective procedures to prevent and supervise I-CRC need to be explored. In this review, we summarized the incidence, causes, risk factors, characteristics and management of I-CRC. It would promote the awareness of the special value in the education and training for the gastroenterologists, which plays an important role in conquering CRC.


Subject(s)
Colonoscopy/standards , Colorectal Neoplasms/diagnosis , Early Detection of Cancer/methods , Mass Screening/methods , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/therapy , Guideline Adherence/statistics & numerical data , Humans , Incidence , Practice Guidelines as Topic , Prevalence , Risk Factors , Time Factors
11.
Transfusion ; 55(9): 2158-67, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25994982

ABSTRACT

BACKGROUND: The operation of cord blood banks (CBBs) requires immense labor, material, and financial resources. Thus, increasing the ratio of high-quality cord blood units (HQCBUs) in storage that are qualified for clinical use is critical for the efficient use of limited resources. Understanding the factors that contribute to HQCBUs, including maternal, fetal, and processing conditions, may improve the number of HQCBUs in storage. STUDY DESIGN AND METHODS: The maternal, fetal, and processing conditions of 4613 CBUs at the Guangzhou Cord Blood Bank were analyzed retrospectively to determine their effect on HQCBUs. All CBUs were obtained following strict standard operation procedures. RESULTS: Several factors may contribute to HQCBUs: fetal age older than 37 gestational weeks, female fetus, large cord blood (CB) volume (>80 mL), high birthweight (>3500 g), vaginal delivery, and a shorter amount of time between CB collection and processing (12 hr). We report for the first time that α-thalassemia carriers exhibit a postprocessing total nucleated cell count (p-TNCC) increase to at least 1.25 × 10(9) and an increase of the CD34+ cell count to at least 6.01 × 10(6) . Meconium-stained amniotic fluid and mothers younger than 25 years of age exhibited increased p-TNCC to at least 1.25 × 10(9) , and colony-forming units increased to at least 23.24 × 10(5) . CONCLUSIONS: We identified several factors that affect HQCBUs. These results may be used as a reference for updating CB collection strategies, with priority given to collecting CBUs from female fetuses older than 37 gestational weeks, at high birthweight, and born by vaginal delivery from mothers younger than 25 years of age, especially newborns with one parent carrying the trait or with meconium-stained amniotic fluid. The collected CBUs should be sent to the laboratory as soon as possible for priority processing, which will help to increase the number and ratio of HQCBUs and the effective use of CBB resources.


Subject(s)
Blood Banks , Donor Selection/methods , Fetal Blood , Adolescent , Adult , Female , Humans , Infant, Newborn , Leukocyte Count , Retrospective Studies , alpha-Thalassemia/blood
12.
Hepatogastroenterology ; 62(140): 790-3, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26902002

ABSTRACT

BACKGROUND/AIMS: Intraoperative blood loss is an independent predictor of recurrence and survival after resection of hepatocellular carcinoma (HCC). The aim of this study was to identify the risk factors associated with intraoperative major blood loss in patients undergoing liver resection for HCC. METHODOLOGY: Clinicopathologic data and perioperative outcomes of 386 patients who underwent liver resection for HCC were retrospectively reviewed. The patients were divided into high (> 1,000 mL) and low (51,000 mL) blood loss groups according to the intraoperative blood loss. Intraoperative blood loss,more than 1,000 mL was defined as major blood loss. The risk factors associated with intraoperative major blood loss were analyzed by univariate and multivariate analyses. RESULTS: Vascular invasion, major hepatectomy and prolonged operation time were risk factors associated with intraoperative major blood loss during resection of HCC on multivariate analysis. Moreover, HCC patients with intraoperative major blood loss had prolonged hospital stay, higher incidence of postoperative complication and mortality compared with patients' with blood loss 1,000 mL. CONCLUSIONS: Vascular invasion, major hepatectomy and prolonged operation time are independent predictors of intraoperative major blood loss during resection of HCC.


Subject(s)
Blood Loss, Surgical/statistics & numerical data , Carcinoma, Hepatocellular/surgery , Hepatectomy , Liver Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Alkaline Phosphatase/blood , Aspartate Aminotransferases/blood , Blood Transfusion , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/pathology , Cohort Studies , Female , Hemorrhage/epidemiology , Hemorrhage/therapy , Hepatic Artery/pathology , Hepatic Veins/pathology , Humans , Intraoperative Complications/epidemiology , Intraoperative Complications/therapy , Length of Stay , Liver Neoplasms/blood , Liver Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness , Operative Time , Retrospective Studies , Risk Factors , Tumor Burden
13.
J Xray Sci Technol ; 23(2): 147-56, 2015.
Article in English | MEDLINE | ID: mdl-25882728

ABSTRACT

Nowadays multi-modality imaging has gained great interest in biology research by offering complementary information. In this paper, a modularly designed fluorescence molecular tomography (FMT) system has been developed, which can be not only used as a standalone imaging device, but also feasibly integrated with other imaging modalities, such as X-ray computed tomography (X-CT), single photon emission computed tomography (SPECT) and positron emission tomography (PET), to perform multi-modality imaging in a sequential manner. The system rotates the CCD camera and the excitation light source in the vertical plane, while the animal is stationed on a horizontally moveable transparent animal holder at its natural prone position. FMT and other imaging modalities are co-registered automatically. Phantom and animal experiments have been carried out to demonstrate the performance of the system. The accurate results show that this innovative flexible FMT system has a great potential to be a powerful tool for the study of small animal disease models.


Subject(s)
Multimodal Imaging/methods , Optical Imaging/methods , Tomography, Optical/methods , Algorithms , Animals , Fluorescent Dyes/chemistry , Image Processing, Computer-Assisted , Indocyanine Green/chemistry , Mice , Mice, Nude , Phantoms, Imaging
14.
Mol Cell Biochem ; 393(1-2): 283-91, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24792036

ABSTRACT

Glioma-associated oncogene homolog-1 (Gli-1) is considered a marker of Hedgehog pathway activation and is associated with the progression of several cancers. We have previously reported that Gli-1 was correlated with invasion and metastasis in hepatocellular carcinoma (HCC). However, the exact roles and mechanisms of Gli-1 in HCC invasion are unclear. In this study, we found that small interfering RNA mediated down-regulation of Gli-1 expression significantly suppressed adhesion, motility, migration, and invasion of both SMMC-7721 and SK-Hep1 cells. Furthermore, down-regulation of Gli-1 significantly reduced expressions and activities of both matrix metalloproteinase (MMP)-2 and MMP-9. In addition, we found that down-regulation of Gli-1 resulted in up-regulation of E-cadherin and concomitant down-regulation of Snail and Vimentin, consistent with inhibition of epithelial-mesenchymal transition (EMT). Taken together, our results suggest that down-regulation of Gli-1 suppresses HCC cell migration and invasion likely through inhibiting expressions and activations of MMP-2, 9 and blocking EMT.


Subject(s)
Carcinoma, Hepatocellular/genetics , Cell Movement/genetics , Liver Neoplasms/genetics , Transcription Factors/genetics , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/pathology , Matrix Metalloproteinase 2/biosynthesis , Matrix Metalloproteinase 9/biosynthesis , Neoplasm Invasiveness/genetics , RNA, Small Interfering , Signal Transduction/genetics , Transcription Factors/antagonists & inhibitors , Zinc Finger Protein GLI1
15.
J Inflamm Res ; 17: 3335-3352, 2024.
Article in English | MEDLINE | ID: mdl-38800598

ABSTRACT

Ischemic stroke is the most common type of stroke, which is the main cause of death and disability on a global scale. As the primary immune cells in the brain that are crucial for preserving homeostasis of the central nervous system microenvironment, microglia have been found to exhibit dual or even multiple effects at different stages of ischemic stroke. The anti-inflammatory polarization of microglia and release of neurotrophic factors may provide benefits by promoting neurological recovery at the lesion in the early phase after ischemic stroke. However, the pro-inflammatory polarization of microglia and secretion of inflammatory factors in the later phase of injury may exacerbate the ischemic lesion, suggesting the therapeutic potential of modulating the balance of microglial polarization to predispose them to anti-inflammatory transformation in ischemic stroke. Microglia-mediated signaling crosstalk with other cells may also be key to improving functional outcomes following ischemic stroke. Thus, this review provides an overview of microglial functions and responses under physiological and ischemic stroke conditions, including microglial activation, polarization, and interactions with other cells. We focus on approaches that promote anti-inflammatory polarization of microglia, inhibit microglial activation, and enhance beneficial cell-to-cell interactions. These targets may hold promise for the creation of innovative therapeutic strategies.

16.
J Diabetes Investig ; 15(1): 121-130, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37737534

ABSTRACT

AIMS: HNF1B syndrome is caused by defects in the hepatocyte nuclear factor 1B (HNF1B) gene, which leads to maturity-onset diabetes of the young type 5 and congenital organ malformations. This study aimed to identify a gene defect in a patient presenting with diabetes and severe diarrhea, while also analyzing the prevalence of hypomagnesemia and its correlation with the HNF1B genotype. MATERIALS AND METHODS: Whole exome sequencing was used to identify responsible point mutations and small indels in the proband and their family members. Multiplex ligation-dependent probe amplification was carried out to identify HNF1B deletions. Furthermore, an analysis of published data on 539 cumulative HNF1B cases, from 29 literature sources, was carried out to determine the correlation between the HNF1B genotype and the phenotype of serum magnesium status. RESULTS: Using multiplex ligation-dependent probe amplification, we identified a de novo heterozygous HNF1B deletion in the patient, who showed dorsal pancreas agenesis and multiple kidney cysts, as detected by magnetic resonance imaging. Magnesium supplementation effectively alleviated the symptoms of diarrhea. Hypomagnesemia was highly prevalent in 192 out of 354 (54.2%) patients with HNF1B syndrome. Compared with patients with intragenic mutations, those with HNF1B deletions were more likely to suffer from hypomagnesemia, with an odds ratio of 3.1 (95% confidence interval 1.8-5.4). CONCLUSIONS: Hypomagnesemia is highly prevalent in individuals with HNF1B syndrome, and those with HNF1B deletion are more susceptible to developing hypomagnesemia compared with those with intragenic mutations. The genotype-phenotype associations in HNF1B syndrome have significant implications for endocrinologists in terms of genotype detection, treatment decisions and prognosis assessment.


Subject(s)
Diabetes Mellitus, Type 2 , Magnesium , Humans , Diabetes Mellitus, Type 2/complications , Diarrhea/complications , Hepatocyte Nuclear Factor 1-beta/genetics , Mutation , Syndrome
17.
Sci Rep ; 14(1): 6772, 2024 03 21.
Article in English | MEDLINE | ID: mdl-38514705

ABSTRACT

Liver diseases, including NAFLD, are a growing worldwide health concern. Currently, there is a lack of suitable in vitro models that sustain basic primary human hepatocyte (PHH) morphology and functionality while supporting presentation of disease-associated phenotypic characteristics such as lipid accumulation and inflammasome activation. In TruVivo, an all-human triculture system (hTCS), basic metabolic functions were characterized in PHHs isolated from normal or diseased livers during two-weeks of culture. Decreases in albumin and urea levels and CYP3A4 activity were seen in diseased-origin PHHs compared to normal PHHs along with higher CYP2E1 expression. Positive expression of the macrophage markers CD68 and CD163 were seen in the diseased PHH preparations. Elevated levels of the pro-inflammatory cytokines IL-6 and MCP-1 and the fibrotic markers CK-18 and TGF-ß were also measured. Gene expression of FASN, PCK1, and G6PC in the diseased PHHs was decreased compared to the normal PHHs. Further characterization revealed differences in lipogenesis and accumulation of intracellular lipids in normal and diseased PHHs when cultured with oleic acid and high glucose. TruVivo represents a promising new platform to study lipogenic mechanisms in normal and diseased populations due to the preservation of phenotypic differences over a prolonged culture period.


Subject(s)
Hepatocytes , Non-alcoholic Fatty Liver Disease , Humans , Hepatocytes/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Cytochrome P-450 CYP2E1/metabolism , Albumins/metabolism
18.
Cell Metab ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38897198

ABSTRACT

Immune checkpoint blockade has led to breakthroughs in the treatment of advanced gastric cancer. However, the prominent heterogeneity in gastric cancer, notably the heterogeneity of the tumor microenvironment, highlights the idea that the antitumor response is a reflection of multifactorial interactions. Through transcriptomic analysis and dynamic plasma sample analysis, we identified a metabolic "face-off" mechanism within the tumor microenvironment, as shown by the dual prognostic significance of nicotinamide metabolism. Specifically, macrophages and fibroblasts expressing the rate-limiting enzymes nicotinamide phosphoribosyltransferase and nicotinamide N-methyltransferase, respectively, regulate the nicotinamide/1-methylnicotinamide ratio and CD8+ T cell function. Mechanistically, nicotinamide N-methyltransferase is transcriptionally activated by the NOTCH pathway transcription factor RBP-J and is further inhibited by macrophage-derived extracellular vesicles containing nicotinamide phosphoribosyltransferase via the SIRT1/NICD axis. Manipulating nicotinamide metabolism through autologous injection of extracellular vesicles restored CD8+ T cell cytotoxicity and the anti-PD-1 response in gastric cancer.

19.
Carcinogenesis ; 34(1): 10-9, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22948179

ABSTRACT

The aberrant activation of sonic hedgehog (SHH) pathway contributes to initiation and progression of various malignancies. However, the roles and underlying mechanisms of SHH signaling pathway in invasion and metastasis of liver cancer have not been well understood. In this study, we found that SHH signaling was activated and correlated with invasion and metastasis in hepatocellular carcinoma (HCC). Enhanced SHH signaling by recombinant human SHH N-terminal peptide (rSHH-N) promoted hepatoma cell adhesion, migration and invasion, whereas blockade of SHH signaling with SHH neutralizing antibody or cyclopamine suppressed hepatoma cell adhesion, migration and invasion. Furthermore, matrix metalloproteinase (MMP)-2 and MMP-9 expressions and activities were upregulated and downregulated by rSHH-N and SHH signaling inhibitor, respectively. The rSHH-N-mediated hepatoma cell migration and invasion was blocked by MMP-specific inhibitors or neutralizing antibodies to MMP-2 and MMP-9. In addition, phosphorylations of AKT and focal adhesion kinase (FAK) were increased and decreased by rSHH-N and SHH signaling inhibitor, respectively. Further investigations showed that activation of AKT and FAK were required for rSHH-N-mediated upregulation of MMP-2 and MMP-9, cell migration and invasion. Finally, we found that SHH protein expression was positively correlated with phosphorylatd FAK Tyr397, phosphorylatd AKT Ser473, MMP-2 and MMP-9 protein expressions in HCC samples. Taken together, our findings suggest that SHH pathway induces cell migration and invasion through FAK/AKT signaling-mediated MMP-2 and MMP-9 production and activation in liver cancer.


Subject(s)
Cell Movement , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Hedgehog Proteins/metabolism , Liver Neoplasms/pathology , Neoplasm Invasiveness , Peptide Hydrolases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Enzyme Activation , Humans , Liver Neoplasms/enzymology
20.
Micromachines (Basel) ; 14(6)2023 May 27.
Article in English | MEDLINE | ID: mdl-37374713

ABSTRACT

Chemical Oxygen Demand (COD) is one of the indicators of organic pollution in water bodies. The rapid and accurate detection of COD is of great significance to environmental protection. To address the problem of COD retrieval errors in the absorption spectrum method for fluorescent organic matter solutions, a rapid synchronous COD retrieval method for the absorption-fluorescence spectrum is proposed. Based on a one-dimensional convolutional neural network and 2D Gabor transform, an absorption-fluorescence spectrum fusion neural network algorithm is developed to improve the accuracy of water COD retrieval. Results show that the RRMSEP of the absorption-fluorescence COD retrieval method is 0.32% in amino acid aqueous solution, which is 84% lower than that of the single absorption spectrum method. The accuracy of COD retrieval is 98%, which is 15.3% higher than that of the single absorption spectrum method. The test results on the actual sampled water spectral dataset demonstrate that the fusion network outperformed the absorption spectrum CNN network in measuring COD accuracy, with the RRMSEP improving from 5.09% to 1.15%.

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