This study investigated the regulatory role of nerve growth factor (NGF) in sirtuin 1 (SIRT1) expression in cholestatic livers. We evaluated the expression of NGF and its cognate receptors in human livers with hepatolithiasis and the effects of NGF therapy on liver injury and hepatic SIRT1 expression in a bile duct ligation (BDL) mouse model. Histopathological and molecular analyses showed that the hepatocytes of human diseased livers expressed NGF, proNGF (a precursor of NGF), TrkA and p75NTR, whereas only p75NTR was upregulated in hepatolithiasis, compared with non-hepatolithiasis livers. In the BDL model without NGF therapy, p75NTR, but not TrkA antagonism, significantly deteriorated BDL-induced liver injury. By contrast, the hepatoprotective effect of NGF was abrogated only by TrkA and not by p75NTR antagonism in animals receiving NGF therapy. Intriguingly, a positive correlation between hepatic SIRT1 and NGF expression was found in human livers. In vitro studies demonstrated that NGF upregulated SIRT1 expression in mouse livers and human Huh-7 and rodent hepatocytes. Both NGF and proNGF induced protective effects against hydrogen peroxide-induced cytotoxicity in Huh-7 cells, whereas inhibition of TrkA and p75NTR activity prevented oxidative cell death. Mechanistically, NGF, but not proNGF, upregulated SIRT1 expression in human Huh-7 and rodent hepatocytes via nuclear factor (NF)-κB activity, whereas NGF-induced phosphoinositide-3 kinase/Akt, extracellular signal–regulated kinase and NF-κB signaling and SIRT1 activity were involved in its hepatoprotective effects against oxidative injury. These findings suggest that pharmacological manipulation of the NGF/SIRT1 axis might serve as a novel approach for the treatment of cholestatic disease.
Animals ; Bile Ducts ; Cell Death ; Cholestasis ; Hepatocytes ; Humans ; Hydrogen ; In Vitro Techniques ; Ligation ; Liver ; Mice ; Nerve Growth Factor ; Phosphotransferases ; Rodentia ; Sirtuin 1

PURPOSE: Professional hemodialysis (HD) nursing tends to be task-oriented and lack consideration of the client's viewpoint. This study aims to interpret the process of psychosocial adaptation to dealing with HD in people with end-stage renal disease (ESRD). METHODS: A grounded theory guided this study. Theoretical sampling included 15 people receiving HD at the HD center of a hospital from July to November 2010. Participants received an information sheet in writing, a verbal invitation, and informed consent forms before interviews were conducted. A constant comparative data analysis was analyzed using open, axial and selective coding. The computer software ATLAS.ti assisted data management. Credibility, transferability, dependability, and confirmability ensured the rigor of study process. RESULTS: This study identified "adopting life with hemodialysis", which captures the process of the psychosocial adaptation in people with ESRD as one transformation. Four categories that evolved from "adopting HD life" are (a) slipping into, (b) restricted to a renal world, (c) losing self control, and (d) stuck in an endless process. CONCLUSIONS: The findings of this investigation indicate the multidimensional requirements of people receiving maintenance dialysis, with an emphasis on the deficiency in psychosocial and emotional care. The study's findings contribute to clinical practice by increasing the understanding of the experience of chronic HD treatment from the recipient's viewpoint. The better our understanding, the better the care provided will meet the needs of the people receiving HD.
*Adaptation, Psychological ; Adult ; Aged ; Female ; Humans ; Kidney Failure, Chronic/*psychology/therapy ; Male ; Middle Aged ; Qualitative Research ; Renal Dialysis/*psychology

Osteopontin (OPN) is a secretory protein that plays an important role in urinary stone formation. Hydration status is associated with the development of urolithiasis. This study was conducted to examine the effects of dehydration and hydration on OPN expression in the rat kidney. Animals were divided into three groups, control, dehydrated, and hydrated. Kidney tissues were processed for light and electron microscope immunocytochemistry, in situ hybridization, and immunoblot analysis. Dehydration induced a significant increase in OPN protein expression, whereas increased fluid intake induced a decrease in protein expression. Under control conditions, OPN protein and mRNA expression were only detected in the descending thin limb (DTL). Dehydration induced increased expression in the DTL and the development of detectable expression in the thick ascending limb (TAL). In contrast, OPN expression levels declined to less than the controls in the DTL after hydration, while no expression of either protein or mRNA was detectable in the TAL. Immunoelectron microscopy demonstrated that hydration status altered tubular ultrastructure and intracellular OPN expression in the Golgi apparatus and secretory cytoplasmic vesicles. These data confirm that changes in oral fluid intake can regulate renal tubular epithelial cell OPN expression.
Animals ; Control Groups ; Cytoplasmic Vesicles ; Dehydration ; Epithelial Cells ; Extremities ; Golgi Apparatus ; Immunohistochemistry ; In Situ Hybridization ; Kidney* ; Microscopy, Immunoelectron ; Osteopontin* ; Rats* ; RNA, Messenger ; Urinary Calculi ; Urolithiasis

Objective: aaWilson’s disease (WD) is a rare genetic disorder of copper metabolism, and longitudinal follow-up studies are limited. We performed a retrospective analysis to determine the clinical characteristics and long-term outcomes in a large WD cohort. Methods: aaMedical records of WD patients diagnosed from 2006–2021 at National Taiwan University Hospital were retrospectively evaluated for clinical presentations, neuroimages, genetic information, and follow-up outcomes. Results: aaThe present study enrolled 123 WD patients (mean follow-up: 11.12 ± 7.41 years), including 74 patients (60.2%) with hepatic features and 49 patients (39.8%) with predominantly neuropsychiatric symptoms. Compared to the hepatic group, the neuropsychiatric group exhibited more Kayser-Fleischer rings (77.6% vs. 41.9%, p < 0.01), lower serum ceruloplasmin levels (4.9 ± 3.9 vs. 6.3 ± 3.9 mg/dL, p < 0.01), smaller total brain and subcortical gray matter volumes (p < 0.0001), and worse functional outcomes during follow-up (p = 0.0003). Among patients with available DNA samples (n = 59), the most common mutations were p.R778L (allelic frequency of 22.03%) followed by p.P992L (11.86%) and p.T935M (9.32%). Patients with at least one allele of p.R778L had a younger onset age (p = 0.04), lower ceruloplasmin levels (p < 0.01), lower serum copper levels (p = 0.03), higher percentage of the hepatic form (p = 0.03), and a better functional outcome during follow-up (p = 0.0012) compared to patients with other genetic variations. Conclusion aaThe distinct clinical characteristics and long-term outcomes of patients in our cohort support the ethnic differences regarding the mutational spectrum and clinical presentations in WD.

OBJECTIVE: Several clinical studies were performed on multi-segment intramedullary primary spinal cord tumors. However, no clinical study focused on the relationship between different vertebral segments intramedullary tumors involvement and neurological functions, as well as prognosis of the patients. This prospective study was performed to compare clinical analysis on neurological functions and prognosis of the patients with intramedullary spinal cord primary tumors. METHODS: A prospective cohort study was performed in a single medical center, Neurosurgical Department, Peking University Third Hospital. Between Jan. 1, 2010 and Dec. 30, 2015, 135 patients underwent microsurgery for intramedullary primary spinal cord tumors. The intramedullary tumor length occupying 3 or more vertebral body levels was considered as multiple segments intramedullary primary spinal cord tumor, and occupying one or two vertebral body levels considered as seldom segments. Preoperative and postoperative functions were assessed using IJOA (improved Japanese orthopaedic association) scoring system, and analyzed using the appropriate statistical tests. RESULTS: Among the 135 patients, 52 cases had seldom segments intramedullary primary spinal cord tumors, and 83 cases had multiple segments. In the seldom group, 32 (62%) patients presented with normal urine and stool function, 8 (15%) patients with severe dysfunction, 7 (14%) with slight dysfunction, and 5 (9%) with incontinence, and 30 (58%) patients demonstrated various degrees of limbs weakness. The preoperative IJOA scores of the patients were 16.9±2.4. The postoperative IJOA scores at the end of 3 months were 16.6±2.3. The current IJOA scores until the end of the follow-up were 17.5±4.4. In the multiple group, 37 (45%) patients presented with normal urine and stool functions, 26 (31%) patients with slight dysfunction, 11 (13%) with severe dysfunction, and 9 (11%) with incontinence, and 62 (75%) patients demonstrated various degrees of limbs weakness. The preoperative IJOA scores of the patients were 15.6±3.4. The postoperative IJOA scores at the end of 3 months were 15.5±3.8. The current IJOA scores until the end of the follow-up were 16.9±5.8. The difference of presenting urine and stool dysfunction (Z=-1.35, P=0.18) was not statistically significant between the different patient groups. However, the difference of presenting limbs weakness (Z=-2.06, P=0.04) was statistically significant between the two groups. Most patients with multiple segment intramedullary tumors suffered from various limbs weakness. The difference of the preoperative IJOA score (P=0.02) and the postoperative early IJOA score (P=0.004) of the patients was statistically significant between the seldom and multiple segments groups. Preoperative and early postoperative neurological function of the patients was better with seldom segments tumor than with multiple segments tumor. Most patients with multi-segment intramedullary tumors experienced various limbs weakness. However, the difference of long-term neurological function (P=0.12) between the seldom and multiple segments groups was not statistically significant. The neurological function of the patients with multiple segments intramedullary tumor was remarkably improved after physical therapy. CONCLUSION Perioperative neurological function of the patients with seldom segments primary tumor was superior to that of the patients with multiple segments primary tumor, especially for limb strength. The neurological function of the patients with multiple segments intramedullary primary tumor was remarkably improved after physical therapy during long-term follow-up.
Humans ; Microsurgery ; Postoperative Period ; Prognosis ; Prospective Studies ; Retrospective Studies ; Spinal Cord ; Spinal Cord Neoplasms ; Treatment Outcome