-
Agalactosyl IgG induces liver fibrogenesis via Fc gamma receptor 3a on human hepatic stellate cells.The Journal of Pathology Jun 2024The relevance of aberrant serum IgG N-glycosylation in liver fibrosis has been identified; however, its causal effect remains unclear. Because hepatic stellate cells...
The relevance of aberrant serum IgG N-glycosylation in liver fibrosis has been identified; however, its causal effect remains unclear. Because hepatic stellate cells (HSCs) contribute substantially to liver fibrosis, we investigated whether and through which mechanisms IgG N-glycosylation affects the fibrogenic properties of HSCs. Analysis of serum IgG N-glycome from 151 patients with chronic hepatitis B or liver cirrhosis revealed a positive correlation between Ishak fibrosis grading and IgG with agalactosyl N-glycoforms on the crystallizable fragment (Fc). Fc gamma receptor (FcγR) IIIa was observed in cultured human HSCs and HSCs in human liver tissues, and levels of FcγRIIIa in HSCs correlated with the severity of liver fibrosis. Additionally, agalactosyl IgG treatment caused HSCs to have a fibroblast-like morphology, enhanced migration and invasion capabilities, and enhanced expression of the FcγRIIIa downstream tyrosine-protein kinase SYK. Furthermore, agalactosyl IgG treatment increased fibrogenic factors in HSCs, including transforming growth factor (TGF)-β1, total collagen, platelet-derived growth factor subunit B and its receptors, pro-collagen I-α1, α-smooth muscle actin, and matrix metalloproteinase 9. These effects were more pronounced in HSCs that stably expressed FCGR3A and were reduced in FCGR3A knockout cells. Agalactosyl IgG and TGF-β1 each increased FCGR3A in HSCs. Furthermore, serum TGF-β1 concentrations in patients were positively correlated with agalactosyl IgG levels and liver fibrosis severity, indicating a positive feedback loop involving agalactosyl IgG, HSC-FcγRIIIa, and TGF-β1. In conclusion, agalactosyl IgG promotes fibrogenic characteristics in HSCs through FcγRIIIa. © 2024 The Pathological Society of Great Britain and Ireland.
PubMed: 38886892
DOI: 10.1002/path.6303 -
American Journal of Translational... 2024To investigate the effectiveness of Alfacalcidol combined with Calcitonin in the treatment of osteoporosis and its influence on the degree of pain, bone metabolism...
OBJECTIVE
To investigate the effectiveness of Alfacalcidol combined with Calcitonin in the treatment of osteoporosis and its influence on the degree of pain, bone metabolism indexes, bone mineral density and inflammatory factor levels.
METHODS
In this retrospective study, 110 patients with osteoporosis treated in The Second Affiliated Hospital of Shandong First Medical University from January 2019 to June 2021 were selected as the study subjects. According to different treatment methods, these patients were divided into an observation group and a control group with 55 cases in each group. Patients from the control group were treated with the alfacalcidol capsules alone, while those from the observation group were treated with the alfacalcidol capsules combined with intramuscular calcitonin injection. Patients in both groups were treated for 6 months continuously. The treatment effect, visual analogue scale (VAS) score and Oswestry disability index (ODI), bone mineral density (BMD), serum markers levels such as calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase-5b (TRACP-5b), insulin-like growth factor (IGF-1), type I procollagen amino terminal propeptide (PINP) and β-collagen special sequence (β-Crosslaps), the levels of inflammatory factor including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), quality Life Questionnaire Core 30 (QLQ-C30) scores and incidences of adverse reactions were evaluated and compared between the two groups.
RESULTS
The effective rate of patients in the observation group was 90.91%, which was significantly higher than 74.54% in the control group (P<0.05). There was no significant difference in the term of VAS score, ODI score, serum markers levels, bone mineral density, inflammatory levels, QLQ-C30 before treatment between the two groups. Compared with the control group, the post-treatment VAS score, ODI score, the levels of IL-6, TNF-α, TRACP-5b, PINP and β-Crosslaps in the observation group were obviously lower, while the post-treatment QLQ-C30, bone mineral density, Ca, P, ALP, IGF-1 levels were significantly higher (all P<0.05). No statistical differences were found in the incidences of adverse reactions between the two groups (P>0.05).
CONCLUSION
The combination of Alfacalcidol combined with Calcitonin is effective in the treatment of osteoporosis patients, which can effectively improve the levels of bone metabolism indexes and bone mineral density, alleviate the symptoms, enhance the life quality and reduce the levels of inflammation. Therefore, it is worth promoting.
PubMed: 38883381
DOI: 10.62347/ZMAL4724 -
F1000Research 2023This study aimed to quantify the mechanoresponse of 10 blood marker candidates for joint metabolism to a walking stress test in patients with knee osteoarthritis and to...
BACKGROUND
This study aimed to quantify the mechanoresponse of 10 blood marker candidates for joint metabolism to a walking stress test in patients with knee osteoarthritis and to determine the association among marker kinetics and with accumulated load and patient reported outcomes.
METHODS
24 patients with knee osteoarthritis completed questionnaires, and a 30-minute walking stress test with six blood serum samples and gait analysis. Concentrations of cartilage oligomeric matrix protein (COMP), matrix metalloproteinases (MMP)-1, -3, and -9, epitope resulting from cleavage of type II collagen by collagenases (C2C), type II procollagen (CPII), interleukin (IL)-6, proteoglycan (PRG)-4, A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and resistin were determined by enzyme-linked immunosorbent assays, Joint load (moments and compartmental forces) was estimated using musculoskeletal modeling using gait analysis data.
RESULTS
COMP and MMP-3 showed an immediate increase after the walking stress followed by a decrease. MMP-9 and resistin showed a delayed decrease below pre-stress levels. ∆COMP correlated with ∆MMP-3 for most time points. ∆MMP-9 correlated with ∆resistin for most time points. The load-induced increase in blood marker levels correlated among blood markers and time points. C2C and resistin correlated positively and C2C/CPII and MMP2 correlated negatively with load during gait. Immediate relative ∆CPII and ∆MMP1 and delayed relative ∆COMP, ∆IL6, ∆C2C, ∆CPII, ∆MMP1 and ∆MMP3 correlated with the load accumulated during the walking stress. Baseline C2C levels correlated with Knee Osteoarthritis Outcome Score (KOOS) subscales and load-induced changes in MMP-3 with KOOS and Short Form 36 quality of life subscores (P<0.05).
CONCLUSIONS
The distinct and differentiated physiological response to the walking stress depends on accumulated load and appears relevant for patient reported osteoarthritis outcome and quality of life and warrants further investigation in the context of disease progression.ClinicalTrials.gov registration: NCT02622204.
Topics: Humans; Female; Male; Osteoarthritis, Knee; Biomarkers; Middle Aged; Patient Reported Outcome Measures; Aged; Kinetics; Weight-Bearing; Walking
PubMed: 38882712
DOI: 10.12688/f1000research.131702.2 -
European Journal of Gastroenterology &... Jun 2024Many children with Wilson's disease are complicated with dyslipidemia. The aim of this study was to investigate the risk factors for the development of fatty liver...
BACKGROUND AND AIMS
Many children with Wilson's disease are complicated with dyslipidemia. The aim of this study was to investigate the risk factors for the development of fatty liver disease (FLD) in children with Wilson's disease.
METHODS
We evaluated sex, age, weight, the disease course, treatment course, clinical classification, alanine transaminase (ALT), aspartate transaminase, γ-glutamyl transpeptidase, total biliary acid, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, homocysteine, uric acid, fibrinogen (FBG), creatinine, procollagen III N-terminal propeptide, laminin, hyaluronic acid, type IV collagen, and performed receiver operating characteristic curve analysis to investigate the forecast value of individual biochemical predictors and combined predictive indicators to evaluate FLD in Wilson's disease.
RESULTS
The multivariate logistic regression analysis revealed that ALT [odds ratio (OR), 1.011; 95% confidence interval (CI), 1.004-1.02; P = 0.006], uric acid (OR, 1.01; 95% CI, 1.002-1.018; P = 0.017), FBG (OR, 3.668; 95% CI, 1.145-13.71; P = 0.037), creatinine (OR, 0.872; 95% CI, 0.81-0.925; P < 0.001), and laminin (OR, 1.01; 95% CI, 1.002-1.018; P = 0.017) acted as independent risk factors in Wilson's disease complicated with FLD. The receiver operating characteristic curves for combined predictive indicators demonstrated an area under the curve values of 0.872, which was found to be a significant predictors for FLD in Wilson's disease.
CONCLUSIONS
We screened out the most important risk factors, namely ALT, uric acid, creatinine, FBG, and laminin for Wilson's disease complicated with FLD. The joint prediction achieved is crucial for identifying children with Wilson's disease complicated with FLD.
PubMed: 38874972
DOI: 10.1097/MEG.0000000000002801 -
Molecular Biology Reports Jun 2024Liver cirrhosis, a prevalent chronic liver disease, is characterized by liver fibrosis as its central pathological process. Recent advancements highlight the clinical...
BACKGROUND
Liver cirrhosis, a prevalent chronic liver disease, is characterized by liver fibrosis as its central pathological process. Recent advancements highlight the clinical efficacy of umbilical cord mesenchymal stem cell (UC-MSC) therapy in the treatment of liver cirrhosis.
METHODS AND RESULTS
We investigated the pharmacodynamic effects of UC-MSCs and MSC conditional medium (MSC-CM) in vivo, utilizing a carbon tetrachloride (CCl)-induced fibrotic rat model. Concurrently, we assessed the in vitro impact of MSCs and MSC-CM on various cellular process of hepatic stellate cells (HSCs), including proliferation, apoptosis, activation, immunomodulatory capabilities, and inflammatory factor secretion. Our results indicate that both MSCs and MSC-CM significantly ameliorate the pathological extent of fibrosis in animal tissues, reducing the collagen content, serum biochemical indices and fibrosis biomarkers. In vitro, MSC-CM significantly inhibited the activation of the HSC line LX-2. Notably, MSC-CM modulated the expression of type I procollagen and TGFβ-1 while increasing MMP1 expression. This modulation restored the MMP1/TIMP1 ratio imbalance and extracellular matrix deposition in TGFβ-1 induced fibrosis. Both MSCs and MSC-CM not only induced apoptosis in HSCs but also suppressed proliferation and inflammatory cytokine release from activated HSCs. Furthermore, MSCs and MSC-CM exerted a suppressive effect on total lymphocyte activation.
CONCLUSIONS
UC-MSCs and MSC-CM primarily modulate liver fibrosis severity by regulating HSC activation. This study provides both in vivo and in vitro pharmacodynamic evidence supporting the use of MSCs in liver fibrosis treatment.
Topics: Hepatic Stellate Cells; Mesenchymal Stem Cells; Animals; Humans; Liver Cirrhosis; Umbilical Cord; Rats; Mesenchymal Stem Cell Transplantation; Cell Proliferation; Apoptosis; Male; Carbon Tetrachloride; Disease Models, Animal; Culture Media, Conditioned; Rats, Sprague-Dawley; Tissue Inhibitor of Metalloproteinase-1; Cell Line; Cytokines
PubMed: 38874773
DOI: 10.1007/s11033-024-09664-6 -
BMC Endocrine Disorders Jun 2024The aim was to evaluate the effect of metabolic control on bone biomarkers in children with type I diabetes.
BACKGROUND
The aim was to evaluate the effect of metabolic control on bone biomarkers in children with type I diabetes.
MATERIALS AND METHODS
The children were divided into two groups according to their glycated hemoglobin (HbA1c) (%) levels: a group with HbA1c levels < 8% (n = 16) and: a group with HbA1c levels > 8% (n = 18). The serum total oxidative status (TOS) (µmol/L), total antioxidant status (TAS) (mmol/L), alkaline phosphatase (ALP) (IU/L), osteocalcin (OC) (ng/ml), procollagen type-1-N-terminal peptide (P1NP) (ng/ml), and vitamin D (IU) levels and food consumption frequencies were determined.
RESULTS
When patients were classified according to HbA1c (%) levels, those with HbA1c levels < 8% were found to have lower TOS (µmol/L) values (8.7 ± 6.16, 9.5 ± 5.60) and higher serum OC (ng/mL) (24.2 ± 16.92, 22.0 ± 6.21) levels than those with HbA1c levels > 8% (p < 0.05). Regardless of the level of metabolic control, there was a statistically significant association between serum TOS (µmol/L) and P1NP (ng/ml) (p < 0.05) levels, with no group-specific relationship (HbA1c levels <%8 or HbA1c levels >%8).
CONCLUSION
HbA1c and serum TOS levels had an effect on bone turnover biomarkers in individuals with type I diabetes.
Topics: Humans; Diabetes Mellitus, Type 1; Child; Male; Female; Biomarkers; Bone Remodeling; Glycated Hemoglobin; Turkey; Adolescent; Osteocalcin; Alkaline Phosphatase; Procollagen; Prognosis; Peptide Fragments; Oxidative Stress; Vitamin D; Follow-Up Studies
PubMed: 38872156
DOI: 10.1186/s12902-024-01553-0 -
Journal of Thermal Biology May 2024Heat stress (HS) poses a substantial threat to animal growth and development, resulting in declining performance and economic losses. The intestinal system is...
Heat stress (HS) poses a substantial threat to animal growth and development, resulting in declining performance and economic losses. The intestinal system is susceptible to HS and undergoes intestinal hyperthermia and pathological hypoxia. Hypoxia-inducible factor-1α (HIF-1α), a key player in cellular hypoxic adaptation, is influenced by prolyl-4-hydroxylase 2 (PHD2) and heat shock protein 90 (HSP90). However, the comprehensive regulation of HIF-1α in the HS intestine remains unclear. This study aims to explore the impact of HS on pig intestinal mucosa and the regulatory mechanism of HIF-1α. Twenty-four Congjiang Xiang pigs were divided into the control and five HS-treated groups (6, 12, 24, 48, and 72 h). Ambient temperature and humidity were maintained in a thermally-neutral state (temperature-humidity index (THI) < 74) in the control group, whereas the HS group experienced moderate HS (78 < THI <84). Histological examination revealed villus exfoliation after 12 h of HS in the duodenum, jejunum, and ileum, with increasing damage as HS duration extended. The villus height to crypt depth ratio (V/C) decreased and goblet cell number increased with prolonged HS. Quantitative real-time PCR, Western blot, and immunohistochemistry analysis indicated increased expression of HIF-1α and HSP90 in the small intestine with prolonged HS, whereas PHD2 expression decreased. Further investigation in IPEC-J2 cells subjected to HS revealed that overexpressing PHD2 increased PHD2 mRNA and protein expression, while it decreases HIF-1α. Conversely, interfering with HSP90 expression substantially decreased both HSP90 and HIF-1α mRNA and protein levels. These results suggest that HS induces intestinal hypoxia with concomitant small intestinal mucosal damage. The expression of HIF-1α in HS-treated intestinal epithelial cells may be co-regulated by HSP90 and PHD2 and is possibly linked to intestinal hyperthermia and hypoxia.
Topics: Animals; HSP90 Heat-Shock Proteins; Hypoxia-Inducible Factor 1, alpha Subunit; Swine; Intestine, Small; Heat-Shock Response; Epithelial Cells; Intestinal Mucosa; Procollagen-Proline Dioxygenase; Hypoxia-Inducible Factor-Proline Dioxygenases; Cell Line
PubMed: 38870755
DOI: 10.1016/j.jtherbio.2024.103881 -
Frontiers in Endocrinology 2024Liraglutide (Lrg), a novel anti-diabetic drug that mimics the endogenous glucagon-like peptide-1 to potentiate insulin secretion, is observed to be capable of partially... (Review)
Review
INTRODUCTION
Liraglutide (Lrg), a novel anti-diabetic drug that mimics the endogenous glucagon-like peptide-1 to potentiate insulin secretion, is observed to be capable of partially reversing osteopenia. The aim of the present study is to further investigate the efficacy and potential anti-osteoporosis mechanisms of Lrg for improving bone pathology, bone- related parameters under imageology, and serum bone metabolism indexes in an animal model of osteoporosis with or without diabetes.
METHODS
Eight databases were searched from their inception dates to April 27, 2024. The risk of bias and data on outcome measures were analyzed by the CAMARADES 10-item checklist and Rev-Man 5.3 software separately.
RESULTS
Seventeen eligible studies were ultimately included in this review. The number of criteria met in each study varied from 4/10 to 8/10 with an average of 5.47. The aspects of blinded induction of the model, blinding assessment of outcome and sample size calculation need to be strengthened with emphasis. The pre-clinical evidence reveals that Lrg is capable of partially improving bone related parameters under imageology, bone pathology, and bone maximum load, increasing serum osteocalcin, N-terminal propeptide of type I procollagen, and reducing serum c-terminal cross-linked telopeptide of type I collagen (P<0.05). Lrg reverses osteopenia likely by activating osteoblast proliferation through promoting the Wnt signal pathway, p-AMPK/PGC1α signal pathway, and inhibiting the activation of osteoclasts by inhibiting the OPG/RANKL/RANK signal pathway through anti-inflammatory, antioxidant and anti-autophagic pathways. Furthermore, the present study recommends that more reasonable usage methods of streptozotocin, including dosage and injection methods, as well as other types of osteoporosis models, be attempted in future studies.
DISCUSSION
Based on the results, this finding may help to improve the priority of Lrg in the treatment of diabetes patients with osteoporosis.
Topics: Liraglutide; Animals; Osteoporosis; Disease Models, Animal; Glucagon-Like Peptide-1 Receptor; Hypoglycemic Agents; Diabetes Mellitus, Experimental; Bone Density
PubMed: 38868747
DOI: 10.3389/fendo.2024.1378291 -
Cureus Jun 2024Background Although the correlation between reduced skin thickness and reduced bone density has been investigated, no study has evaluated skin thickness and...
Background Although the correlation between reduced skin thickness and reduced bone density has been investigated, no study has evaluated skin thickness and osteoproliferative diseases, including ossification of the posterior longitudinal ligament (OPLL) and diffuse idiopathic skeletal hyperostosis (DISH). Methodology This retrospective cohort study consisted of 99 consecutive patients aged ≥60 years treated for spinal surgery at our hospital between January 2022 and March 2023. Skin thickness was measured at the dorsal side of the cervical, thoracic, and lumbar vertebrae on the sagittal cross-section image of whole-spine CT. Based on the median value, skin thickness was categorized into two groups based on a median thickness of 4 mm. Bone mineral density (BMD) was assessed. The sum of the vertebral body and intervertebral bridging osteophytes of the anterior longitudinal and posterior longitudinal ligament were defined as the OALL index and OPLL index. Serum levels of bone metabolism-related markers, such as tartrate-resistant acid phosphatase type 5b, procollagen I N-propeptide, 25-hydroxyvitamin D, and periostin, were measured. To assess the association between skin thickness and imaging findings, we calculated the adjusted odds ratios, adjusting for age, sex, and body mass index (BMI) and using univariate and multivariate logistic regression analyses. Results No significant differences were found in skin thickness in the three dorsal regions of the cervical, thoracic, and lumbar spine (median = 3.3 mm versus 3.5 mm versus 3.4 mm, p = 0.357) and bone metabolism-related markers. Adjusting for age, sex, and BMI, cervical, thoracic, and lumbar skin thicknesses were related to DISH, the OPLL index, and the OPLL and OPLL index, respectively. Conclusions Skin thickness did not correlate with BMD but with the amount of spinal ossification. A correlation was found between skin thickness and vertebral and intervertebral ossification; vertebral osteophytes, OPLL, and DISH may be more common in thicker skin.
PubMed: 38868545
DOI: 10.7759/cureus.62235 -
BMC Endocrine Disorders Jun 2024Patients with primary hyperparathyroidism (PHPT) are at risk for severe hypocalcemia (SH) following parathyroidectomy (PTX), but limited data exist on the predictors of...
Identification of novel risk factors for postoperative severe hypocalcemia in patients with primary hyperparathyroidism undergoing parathyroidectomy: a case control study.
BACKGROUND
Patients with primary hyperparathyroidism (PHPT) are at risk for severe hypocalcemia (SH) following parathyroidectomy (PTX), but limited data exist on the predictors of SH. We aimed to identify risk factors for early postoperative SH after PTX in patients with PHPT and to evaluate the predictive value of clinical parameters.
METHODS
A retrospective review of patients with PHPT who underwent PTX between January 2010 and December 2022 was performed. A total of 46 patients were included in the study, with 15 (32.6%) experiencing postoperative SH, 19 (41.3%) having calculi in the ureter or kidney, and 37 (80.4%) having osteoporosis. Patients were divided into SH and non-SH groups based on postoperative serum calcium levels. Preoperative biochemical indicators, bone turnover markers, and renal function parameters were analyzed and correlated with postoperative SH.
RESULTS
Statistically significant (P < 0.05) differences were found in preoperative serum calcium (serum Ca), intact parathyroid hormone, serum phosphorus (serum P), serum Ca/P, percentage decrease of serum Ca, total procollagen type 1 intact N-terminal propeptide, osteocalcin (OC), and alkaline phosphatase levels between the two groups. Multivariate analysis showed that serum P (odds ratio [OR] = 0.989; 95% confidence interval [95% CI] = 0.981-0.996; P = 0.003), serum Ca (OR = 0.007; 95% CI = 0.001-0.415; P = 0.017), serum Ca/P (OR = 0.135; 95% CI = 0.019-0.947; P = 0.044) and OC levels (OR = 1.012; 95% CI = 1.001-1.024; P = 0.036) were predictors of early postoperative SH. The receiver operating characteristic curve analysis revealed that serum P (area under the curve [AUC] = 0.859, P < 0.001), serum Ca/P (AUC = 0.735, P = 0.010) and OC (AUC = 0.729, P = 0.013) had high sensitivity and specificity.
CONCLUSION
Preoperative serum P, serum Ca/P and osteocalcin levels may identify patients with PHPT at risk for early postoperative SH after PTX.
Topics: Humans; Hyperparathyroidism, Primary; Female; Male; Parathyroidectomy; Middle Aged; Risk Factors; Retrospective Studies; Case-Control Studies; Hypocalcemia; Postoperative Complications; Aged; Calcium; Prognosis; Biomarkers; Adult; Follow-Up Studies; Parathyroid Hormone
PubMed: 38867205
DOI: 10.1186/s12902-024-01620-6