Serum Hyaluronic Acid Levels Research Articles

The Role of Serum Level of Col2a1 and Hyaluoronic Acid in Diagnosis of Knee Osteoarthritis

Osteoarthritis (OA) is a complex condition in which affected tissues experience changes in metabolism, structure, biochemistry, and function. This condition arises when chondrocytes fail to balance the synthesis and degradation of extracellular components like proteoglycans and collagens, leading to inflammation of the synovial membrane and joint capsule. Aim of the study: This study was designed to evaluate the serum levels of Type II Collagen alpha 1 (coll2a1) and Hyaluronic Acid (HA) in diagnosis of early stage of knee osteoarthritis in Iraqi patients Subjects and Methods: This case- control study was carried out at Department of Biochemistry, College of Medicine, University of Baghdad and at Rheumatology Department , Baghdad Hospital / Medical City, during the period from September 2022 to March 2023. It included ninety volunteer males and females subdivided into subgroups: Group 1consisted of 50 patients who have had early stages of knee osteoarthritis (KOA) and group 2 involved 40 apparently healthy subjects who served as control group. The diagnosis of KOA was made by a consultant rheumatologist using American College of Rheumatology (ACR) criteria. Moreover, patients were sub- classified according to their BMI (normal weight, overweight and obese) and KOA severity (grad1 and grad 2). Investigations included serum measurements of Human serum coll2a1( type II collagen alpha I) and Human serum HA (Hyaluronic Acid) in all patients and controls by ELISA technique. Results: The mean (±SD) values of Coll2a1, HA, of KOA patients were significantly higher than those of controls (for all, p <0.01). There was significant positive correlation between. The mean value of serum hyaluronic acid was significantly increased in grad 2 KOA when compared with grad 1 KOA patients (p < 0.004). The results found that fibulin-3 has the highest receiver operator characteristic (ROC) and area under curve (AUC=89.2% ) at cutoff (7.50 ng/ml) with sensitivity 80.0 and specificity 80.0 in diagnosis of KOA. Also, serum Coll2a1 has high diagnostic utility (AUC=88.6%) at cutoff (286.00 pg/ml) with sensitivity 82.0 and specificity 80.0 . Conclusion: Assessing non-invasive serum levels of coll2a1 (with a cutoff of 286.00 pg/ml) offers a new biochemical marker for diagnosing the early stages of knee osteoarthritis (KOA) potentially before changes become visible on X-rays. Additionally, measuring serum hyaluronic acid levels could serve as an indicator of disease severity, helping to differentiate between various grades of KOA.

Huangqi Decoction reduces liver fibrosis in rats by modulating PI3K/Akt/mTOR signaling and promoting autophagy.

Liver fibrosis is a chronic condition caused by various factors, and currently, there are no widely effective treatments. Autophagy plays a crucial role in maintaining liver energy homeostasis, and its disruption can contribute to the development of liver fibrosis. This study investigates the effects and molecular mechanisms of Huangqi Decoction, a traditional Chinese medicine, on autophagy and apoptosis in fibrotic liver tissue. Tissue staining indicated that Huangqi Decoction mitigated CCL4-induced liver injury and apoptosis in rats. Western blot analysis of liver fibrosis markers revealed that Huangqi Decoction significantly reduced the expression levels of alpha-smooth muscle actin (α-SMA), type I collagen, matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9). Additionally, serum markers of liver fibrosis and biochemical indicators of hepatocyte injury showed that Huangqi Decoction effectively lowered serum levels of hyaluronic acid (HA), lymph node (LN), type I collagen, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Furthermore, Western blot analysis confirmed that Huangqi Decoction alleviated hepatocyte injury by promoting autophagy and inhibiting the PI3K/Akt/mTOR signaling pathway. In conclusion, Huangqi Decoction enhances autophagy and inhibits apoptosis through the PI3K/Akt/mTOR pathway in rats with liver fibrosis.

The correlation between serum levels of laminin, type IV collagen, type III procollagen N-terminal peptide and hyaluronic acid with the progression of post-COVID-19 pulmonary fibrosis.

COVID-19 patients often suffer from post-COVID-19 acute sequelae (PASC). Pulmonary fibrosis has the most significant long-term impact on the respiratory health of patients, known as post-COVID-19 pulmonary fibrosis (PC19-PF). PC19-PF can be caused by acute respiratory distress syndrome (ARDS) or COVID-19-induced pneumonia. Individuals who experience COVID-19 pneumonia symptoms (including cough, shortness of breath, dyspnea on exertion, and desaturation) for at least 12 weeks after diagnosis, almost all develop PC19-PF. Extracellular matrix molecules: laminin (LN), type IV collagen (IV Col), procollagen III N-terminal peptide (PIIINP), and hyaluronic acid (HA) are involved in the development and progression of PC19-PF. This study aimed to investigate the relationship between the progression of PC19-PF and serum levels of laminin, IV COL, PIIINP, and hyaluronic acid. This retrospective study included 162 PC19-PF patients treated and 160 healthy controls who received treatment at Shenzhen Longgang District Third People's Hospital, Hebei PetroChina Central Hospital and Changzhi People's Hospital from January 2021 to December 2023. Serum levels of LN, IV COL, PIIINP, and HA were detected by chemiluminescence immunoassay using commercial kits. Predicted forced vital capacity percentage (FVC% pred), predicted carbon monoxide lung diffusion capacity percentage (DLCO% pred), high-resolution computed tomography (HRCT) scores were assessed, and patient mortality was compared with healthy controls. Serum levels of LN, IV Col, PIIINP, and HA were significantly higher in PC19-PF or CTD-ILD patients than in healthy controls (all p < 0.05), and they were further elevated in acute exacerbation cases (all p < 0.01). In patients, HA was positively associated with HRCT scores and negatively associated with FVC% pred and DLCO% pred (all p < 0.05). Serum levels of LN, IV COL, PIIINP, and HA were significantly lower in surviving patients than in those who deceased (all p > 0.05). Serum levels of LN, IV C, PIIINP, and HA may affect the progression of PC19-PF and may serve as indicators of PC19-PF severity.

Analysis of Factors Influencing Prognosis and Assessment of 60 Cases of Decompensated Cirrhotic Patients with Portal Hypertension.

To investigate the risk factors for the development of portal hypertension in patients with decompensated cirrhosis and analyze their prognosis. Patients with decompensated cirrhosis who were admitted to our hospital and Qu fu People's Hospital from June 2022 to June 2023 were included in this study. Among them, there were 45 male and 15 female patients, with a median age of 56 (range: 35-77) years. A comparative analysis was performed between Group A (hepatic venous pressure gradient, HVPG <16 mmHg) and Group B (HVPG ≥16 mmHg) patients, along with various clinical outcomes. Multivariate analysis was conducted to explore the risk factors influencing the occurrence of portal hypertension and adverse prognosis in patients with cirrhosis. In Group A patients with portal hypertension, we observed lower levels of aspartate aminotransferase, laminin, serum hyaluronic acid, type III procollagen N-terminal peptide, total bile acids, and cholylglycine acid compared to Group B. On the other hand, levels of alanine aminotransferase, white blood cells, and serum albumin were higher in Group A than in Group B. These differences between the groups were statistically significant (P < 0.05). Multivariate analysis of the aforementioned risk factors indicated that low white blood cell count, high cholylglycine acid levels, and high serum hyaluronic acid levels were identified as independent risk factors for the occurrence of difficult-to-control complications in decompensated portal hypertension among patients with liver cirrhosis (P < 0.05). Liver cirrhosis patients with portal hypertension and multiple risk factors like low white blood cell count and high liver transaminase levels should be cautious regarding the progression of portal hypertension when combined with splenomegaly, liver fibrosis, and bile stasis, as it often indicates a poor prognosis.

Assessment of hyaluronic acid in COPD patients as a prognostic biomarker

BackgroundOne essential element of the extracellular matrix is hyaluronic acid (HA). It has been claimed that HA and its metabolism are different in the lungs of patients with chronic obstructive pulmonary disease (COPD). The present study investigated the predictive significance of serum level of HA in patients with COPD and monitored changes in its level in these patients because of therapy.MethodsHA was assessed in 60 patients with stable COPD (divided into subgroups I and II) and 20 healthy controls and then repeated after 3 and 6 months in COPD patients.ResultsMost of the patients were males (63.3%), and their ages ranged from 30 to 90. The serum level of HA was significantly increased in subgroups I and II (269.33 ± 4, 290 ± 4, respectively), compared to the control group (147.5 ± 1) with a significant difference in its level between both (p < 0.0001). The serum level of HA was significantly decreased in both subgroups 3 and 6 months later following adjustment of treatment and associated with improvement in pulmonary function test. There were significant positive correlations between HA and age as well as smoking index. Its level correlated negatively with forced expiratory volume in the first second (FEV1%), forced vital capacity (FVC%), and FEV1/FVC.ConclusionsHA is a useful marker for identifying clinical stability in COPD patients and for follow-up in the efficacy of treatment.

Yinhuang granule alleviates carbon tetrachloride-induced liver fibrosis in mice and its mechanism.

Liver fibrosis is a formidable global medical challenge, with no effective clinical treatment currently available. Yinhuang granule (YHG) is a proprietary Chinese medicine comprising Scutellariae Radix and Lonicerae Japonicae Flos. It is frequently used for upper respiratory tract infections, pharyngitis, as well as acute and chronic tonsillitis. To investigate the potential of YHG in alleviating carbon tetrachloride (CCl4)-induced liver fibrosis in mice. To induce a hepatic fibrosis model in mice, this study involved intraperitoneal injections of 2 mL/kg of CCl4 twice a week for 4 wk. Meanwhile, liver fibrosis mice in the low dose of YHG (0.4 g/kg) and high dose of YHG (0.8 g/kg) groups were orally administered YHG once a day for 4 wk. Serum alanine/aspartate aminotransferase (ALT/AST) activity and liver hydroxyproline content were detected. Sirius red and Masson's trichrome staining assay were conducted. Real-time polymerase chain reaction, western-blot and enzyme-linked immunosorbent assay were conducted. Liver glutathione content, superoxide dismutase activity level, reactive oxygen species and protein carbonylation amount were detected. The administration of YHG ameliorated hepatocellular injury in CCl4-treated mice, as reflected by decreased serum ALT/AST activity and improved liver histological evaluation. YHG also attenuated liver fibrosis, evident through reduced liver hydroxyproline content, improvements in Sirius red and Masson's trichrome staining, and lowered serum hyaluronic acid levels. Furthermore, YHG hindered the activation of hepatic stellate cells (HSCs) and ameliorated oxidative stress injury and inflammation in liver from CCl4-treated mice. YHG prompted the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated the expression of Nrf2-dependent downstream antioxidant genes. In addition, YHG promoted mitochondrial biogenesis in liver from CCl4-treated mice, as demonstrated by increased liver adenosine triphosphate content, mitochondrial DNA levels, and the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha and nuclear respiratory factor 1. YHG effectively attenuates CCl4-induced liver fibrosis in mice by inhibiting the activation of HSCs, reducing inflammation, alleviating liver oxidative stress damage through Nrf2 activation, and promoting liver mitochondrial biogenesis.

Serologic Biomarkers for Hepatic Fibrosis in Obese Children with Nonalcoholic Steatohepatitis.

The prevalence of nonalcoholic steatohepatitis (NASH) is increasing with the increasing prevalence of childhood obesity. Although NASH has a high risk of progression to liver fibrosis and cirrhosis, few studies have reported noninvasive markers for predicting hepatic fibrosis in children. This study aimed to evaluate and compare the diagnostic accuracies of serologic biomarkers and scoring systems for hepatic fibrosis in obese children with NASH. A total of 96 children were diagnosed with NASH based on liver biopsy findings and divided into two groups according to the degree of liver fibrosis: mild (stage 0-1) or advanced (stage 2-4). Clinical and laboratory parameters and serum levels of hyaluronic acid and type IV collagen were measured. The aspartate aminotransferase/platelet ratio index (APRI) and fibrosis-4 (FIB-4) score were calculated. Among the noninvasive markers, only serum type IV collagen level and FIB-4 were significantly different between the two groups. The area under the receiver operating curve of each biomarker and scoring system was 0.80 (95% confidence interval [CI]: 0.70-0.90) for type IV collagen at an optimal cutoff of 148 ng/mL (sensitivity 69.8%, specificity 84.6%), followed by 0.69 (95% CI: 0.57-0.83) for APRI, 0.68 (95% CI: 0.56-0.80) for FIB-4, and 0.65 (95% CI: 0.53-0.77) for hyaluronic acid. Type IV collagen as a single noninvasive serologic biomarker for hepatic fibrosis and FIB-4 as a hepatic fibrosis score are beneficial in predicting advanced hepatic fibrosis and determining proper diagnosis and treatment strategies before fibrosis progresses in obese children with NASH.

Serum Hyaluronic Acid- An Effective Biomarker for Early Detection of Osteoarthritis in Young Dogs with Canine Hip Dysplasia

Background: Most of the biomarkers used in joint disease are articular cartilage components such as chondroitin sulphate (CS), keratan sulphate (KS), hyaluronic acid (HA), or type II collagen. Some of these biomarkers, alone or together, could have the potential to provide clinically useful indices of the effects of isolated joint injury, the progression of joint changes and/or the response to therapy. Serum concentration of HA were elevated in human patients with osteoarthritis which increase is considered a reliable biomarker reflective of cartilage damage and synovitis in these patients. Methods: Blood samples were collected from all the dogs and serum concentration of hyaluronic acid was determined by Canine Hyaluronic Acid Elisa kit (catalogue No.ITE070452), SIZE -96T, Reactivity: Canine, Range: 2 ng/ml -700ng/ml and sensitivity: 1.04 ng/ml, supplied by G Biosciences. Result: Serum concentration of HA were lower in dogs aged between 0 to 12 months with CHD when compared to dogs of similar age with healthy hip joints and that this significant decrease in serum HA in dogs can be considered a reliable biomarker reflective of CHD and serum HA levels can be used as an effective biomarker for osteoarthritis in dogs with CHD.

Occult Hepatitis B Virus Infection and Liver Fibrosis in Chinese Patients.

The impact of hepatitis B surface antigen (HBsAg)-negative/hepatitis B virus (HBV) DNA-positive occult HBV infection (OBI) on the severity of liver fibrosis remains unclear. A total of 1772 patients negative for HBsAg but positive for antibody to hepatitis B core antigen (HBcAg), stratified by the presence or absence of OBI, were selected for long-term carriage leading to elevation of ≥2 of 4 liver fibrosis indexes-hyaluronic acid (HA), laminin, type III procollagen peptide (PCIII), and type IV collagen (CIV)-at testing in a Chinese hospital. Patients were tested for serum viral load, HBV markers, and histopathological changes in liver biopsy specimens. OBI was identified in 148 patients with liver fibrosis (8.4%), who had significantly higher levels of HA, laminin, PCIII, and CIV than 1624 fibrotic patients without OBI (P < .05). In 36 patients with OBI who underwent liver biopsy, significant correlations were observed between OBI viral load and serum HA levels (P = .01), PCIII levels (P = .01), and pathological histological activity index (HAI) scores (P < .001), respectively; HAI scores and PCIII levels (P = .04); HBcAg immunohistochemical scores and HA levels (P < .001); and HBcAg immunohistochemical scores and PCIII levels (P = .03). Positive fluorescent in situ hybridization results were significantly more frequent in patients with OBIs (80.6% vs 37.5% in those without OBIs). Among patients with OBIs, HBcAg was detected in the liver tissue in 52.8% and HBsAg in 5.6%. OBI status appears to be associated with liver fibrosis severity.

The hepatoprotective effect of aspirin on carbon tetrachloride‑induced hepatic fibrosis via inhibition of TGFβ‑1 pathway and pro‑inflammatory cytokines IL‑1β and COX‑2 in rats.

Aspirin decreases liver fibrosis index and inflammation levels. However, the exact mechanism underlying the effects of aspirin are yet to be elucidated. The aim of the study was to investigate the potential protective effects of aspirin on carbon tetrachloride (CCl4)-induced hepatic fibrosis in Sprague-Dawley rats. Rats were divided into four groups, including healthy and CCl4 control and low-(aspirin 10 mg/kg + CCl4) and high-dose aspirin group (aspirin 300 mg/kg + CCl4). After 8 weeks treatment, the histopathological examinations of hepatocyte fibrosis in liver and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), IL-1β, transforming growth factor-β1 (TGF-β1), hyaluronic acid (HA), laminin (LN) and type IV collagen (IV.C) were determined. Histopathological examination suggested that aspirin decreased CCl4-induced hepatic fibrosis and liver inflammation. The high-dose aspirin group significantly decreased the serum levels of ALT, AST, HA and LN compared with the CCl4 control group. High-dose aspirin group significantly decreased the levels of pro-inflammatory cytokines IL-1β compared with CCl4 group. The high-dose aspirin group significantly inhibited the expression of TGFβ-1 protein compared with CCl4 group. Overall, the present study indicated that aspirin exhibited potent protective effects against CCl4-induced hepatic fibrosis via inhibition of the TGFβ-1 pathway and pro-inflammatory cytokine IL-1β.

Nicorandil reduces morphine withdrawal symptoms, potentiates morphine antinociception, and ameliorates liver fibrosis in rats

AimsChronic liver disease (CLD) is a serious medical condition affecting patients globally and pain management poses a unique challenge. ATP-sensitive potassium channels (KATP) are expressed in nociceptive neurons and hepatic cells. We tested the hypothesis whether morphine and nicorandil, KATP channel opener, alone and in combination possess hepatoprotective, antinociceptive effect and alter morphine physical dependence. Main methodsIntraperitoneal injection (i.p.) of carbon tetrachloride (CCl4) induced liver fibrosis in male Wistar rats. Nicorandil (15 mg/kg/day) was administered per os for two weeks. Morphine (3.8, 5, 10 mg/kg, i.p.) was administered prior to antinociception testing in tail flick and formalin tests. Morphine physical dependence following naloxone injection, fibrotic, oxidative stress markers, and liver histopathology were assessed. Key findingsMorphine alone, produced insignificant changes of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), hepatic hydroxyproline (Hyp), malondialdehyde (MDA), and superoxide dismutase (SOD) levels and exerted significant antinociception in the pain models. Nicorandil alone protected against liver damage (decreased serum ALT, AST, HA, hepatic Hyp, MDA, increased SOD levels, improved fibrosis scores). Nicorandil/morphine combination produced remarkable hepatoprotection and persistent analgesia compared to morphine alone as evidenced by reduced (EC50) of morphine. Nicorandil augmented morphine analgesia and markedly decreased withdrawal signs in morphine-dependent rats. SignificanceThe data showed for the first time, the hepatoprotection and augmented antinociception mediated by nicorandil/morphine combination in liver fibrosis via antioxidant and antifibrotic mechanisms. Nicorandil ameliorated withdrawal signs in morphine dependence in CLD. Thus, combining nicorandil/morphine provides a novel treatment strategy to ameliorate hepatic injury, potentiate antinociception and overcome morphine-induced physical dependence in liver fibrosis.

Serum 25-hydroxyvitamin D and hyaluronic acid levels as markers of fibrosis in patients with chronic liver disease at the main tertiary referral hospital in Ghana: A case-control study design.

Liver fibrosis leading to chronic liver disease (CLD) is a major cause of morbidity, mortality and health-care expenditure worldwide. The "gold standard" for diagnosis and staging of liver fibrosis is histological analysis of liver tissue obtained by liver biopsy, an invasive procedure. Therefore, there is the need to identify noninvasive and inexpensive markers for diagnosis and staging of liver fibrosis. This study aimed at evaluating the correlation of hyaluronic acid (HA) and 25-hydroxyvitamin D (25-OH vitamin D) serum levels as markers of fibrosis with histologically staged and graded liver biopsies obtained from CLD patients. This was a case-control study involving 40 CLD patients requiring liver biopsies and 40 controls. Liver biopsies were staged to determine the degree of fibrosis. Serum levels of 25-OH vitamin D and HA were determined using ELISA. Statistical analyses were performed to determine differences in HA and 25-OH vitamin D levels between controls and patients as well as to correlate the biomarkers with the stages of fibrosis. CLD patients showed significant (p < 0.001) increase in the levels of AST, ALT, GGT, compared to the controls. Patients also had significantly (p < 0.001) lower serum 25-OH vitamin D and higher HA (p < 0.001) levels compared to the controls. Additionally, 25-OH vitamin D levels of the CLD patients were significantly different across the stages of liver fibrosis likewise serum HA levels. Furthermore, 25-OH vitamin D levels inversely correlated with the severity of liver fibrosis. A significant negative correlation (r = -0.33, p < 0.05) between CLD patients' HA and 25-OH vitamin D were found. CLD patients had significantly reduced serum 25-OH vitamin D and higher HA. Both markers correlated with the degree of liver fibrosis. These findings have major clinical translatable implication in the use of vitamin D supplementation in the management of CLD in Ghana.

Accuracy of noninvasive methods for the diagnosis of liver fibrosis in children with chronic viral hepatitis.

Liver biopsy is the reference standard for assessing liver fibrosis. Moreover, it is an invasive procedure. Transient elastography (TE) is an accurate, noninvasive method for evaluating liver stiffness as a surrogate of liver fibrosis. The aspartate aminotransferase to platelet ratio index (APRI) and Hyaluronic acid (HA) are noninvasive alternatives to liver biopsy for detecting hepatic fibrosis. This study aimed to identify the accuracy of APRI, HA, and TE concerning liver biopsy in children with chronic viral hepatitis. This cross-sectional study included 50 children, 5-18years with chronic viral hepatitis B (HBV) or hepatitis C (HCV) who underwent liver biopsy within nine months of laboratory tests, determining APRI & performing TE. Twenty healthy children of age and sex-matching patients were included as a control group for the serum HA levels. The histopathological findings of the studied cases showed seven cases with (F0) fibrosis, 36 cases with mild (F1,2), two children with moderate (F3,4), and five children with severe (F5,6). The median (IQR) of steatosis was 4 (three had HCV). When correlating TE, APRI, and HA values in all cases with their laboratory data, there was a positive correlation between ALT and APRI values (P-value = 0.000), a positive correlation between AST and HA values (P-value = 0.02), and a negative correlation between stiffness and APRI. The sensitivity of HA, APRI, and TE compared to fibrosis detected by histopathology was 60.5, 65.1, and 60.5%, and their specificity was 71.4, 57.1, and 85.7%, respectively. TE was significantly higher in a group with (moderate to severe) fibrosis. APRI, HA, and TE are good indicators of the presence of fibrosis almost with the same accuracy. TE is the only method to differentiate mild cases from those with significant fibrosis.

The Association Between Serum Hyaluronic Acid Levels and Routine Liver Function Tests in Liver Fibrotic HCV Patients

Abstract Introduction/Objective Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, that occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and often requires liver transplantation. Markers (NIM) of Liver Fibrosis, such as hyaluronic acid, help evaluate the stage of fibrosis in patients with liver fibrosis. This study aims to investigate whether or not there is a correlation between serum hyaluronic acid levels and liver function tests in patients who suffer from chronic HCV-induced liver fibrosis. Methods/Case Report This study was conducted on 118 (60 males and 58 females) patients recruited from Internal Medicine Dept., Mansoura University Hospitals, Egypt. The patients were diagnosed with chronic HCV-induced liver fibrosis. Also, we included 50 healthy comparable control subjects (27 males and 23 females). Routine laboratory tests such as AST, ALT, albumin, total bilirubin, and platelets count were performed. The APRI was calculated as [AST/ (upper limits of normal)/ platelets count 109/L]×100. The AST-ALT ratio was calculated as [AST/ ALT]. According to the manufacturer's instructions, the serum levels of hyaluronic acid were measured by radioimmunoassay. Results (if a Case Study enter NA) We observed a statistically significant positive correlation was found between serum hyaluronic acid levels and APRI (r=0.3, p=0.001), ALT (r=0.3, p=0.003), AST (r=0.3 and p=0.01), and total bilirubin (r=0.3 and p=0.002). Furthermore, there was a statistically significant negative correlation between serum hyaluronic acid levels and albumin (r= -0.43, p=0.0001), and platelets count (r= -0.4, p=0.0001). Conclusion The levels of hyaluronic acid in the body and the results of other liver function tests tend to rise in tandem, which suggests a significant relationship between the two. This may assist us in constructing an accurate picture of the patient's condition, which will lead to a more precise diagnosis.

Protective effect of active vitamin D on liver fibrosis induced by sodium arsenite in SD rats

To explore the protective effect of active vitamin D(VD) on liver fibrosis injury induced by sodium arsenite(NaAsO_2) in SD rats. Eighteen healthy newly weaned SD rats, half male and half female, were randomly divided into Control group(gavaged with 10 mL/kg normal saline), NaAsO_2-treated group(gavaged with 10 mg/kg NaAsO_2), Active VD(calcitriol) intervention group(gavaged with 10 mg/kg NaAsO_2 and 1.0 μg/kg calcitriol was given by gavage along with NaAsO_2 administration after 12 weeks), all rats were administered 6 days a week for 36 weeks and weighed every week. Enzyme-linked immunosorbent(ELISA) was used to detect the secretion levels of 25(OH)D_3 and hyaluronic acid(HA), laminin(LN), type Ⅲ pre-collagen amino-terminal peptide(PⅢNP), type Ⅳ collagen(COL-Ⅳ) in the serum of rats in each group; HE staining was used to observe the basic pathological changes of liver tissues in each group, Masson and Sirius Red staining were used to observe the fibrosis and collagen deposition of liver tissues in each group; Western Blot was used to detected the protein levels of fibrosis-related markers α-smooth actin(α-SMA), transforming growth factor-β1(TGF-β1) and Vimentin in each group. After 36 weeks of NaAsO_2 exposure, the weight of rats was significantly decreased compared with the control group, and the weight of female rats after calcitriol intervention was significantly increased compared with NaAsO_2-treated group(P&lt;0.05). The result of liver coefficient showed increasing in NaAsO_2-treated group compared with the control group, while decreasing in calcitriol intervention group compared with NaAsO_2-treated group, and the difference was statistically significant in female rats. ELISA assay showed that compared with the control group((550.21±29.16) ng/L), the serum level of 25(OH)D_3 in NaAsO_2-treated group((436.82±74.37) ng/L) was significantly decreased(P&lt;0.05), while the serum level of 25(OH)D_3 was significantly higher in calcitriol intervention group than that of NaAsO_2-treated group(P&lt;0.05). HE staining found that, compared with the control group, the liver tissue of rats in NaAsO_2-treated group showed abnormal morphology, the liver tissue was structurally disordered, false lobules and fat vacuoles were also increased. Masson and Sirius Red staining also revealed abnormal hepatic lobule structure, enlarged and deformed portal area and abundant collagen fiber deposition in NaAsO_2-treated group. Further analysis showed that the positive staining area of collagen deposition in liver tissue of rats exposed to NaAsO_2 increased significantly compared with the control group(P&lt;0.05). Those above changes in calcitriol intervention group were significantly alleviated compared with NaAsO_2-treated group(P&lt;0.05). Western Blot analysis showed that the protein levels of α-SMA, TGF-β1 and Vimentin were obviously higher in NaAsO_2-treated group(1.12±0.21, 1.12±0.26, 1.31±0.15) than that in the control group(0.57±0.10, 0.64±0.13, 0.72±0.16)(P&lt;0.05). In addition, the serum levels of HA, LN, PⅢNP and COL-Ⅳ in rats exposed to NaAsO_(2 )((87.92±9.67), (89.04±11.91), (12.09±2.97) and(19.86±3.40)ng/mL) were also higher than those in control group. After calcitriol intervention, the protein levels of α-SMA, TGF-β1 and Vimentin(0.68±0.16, 0.85±0.21, 0.84±0.09) in liver tissue and the serum levels of HA, LN, PⅢNP and COL-Ⅳ((54.29±7.23), (55.56±9.43), (6.49±1.08), (10.15±1.99) ng/mL) were significantly lower than those of NaAsO_2-treated group(P&lt;0.05). Calcitriol can effectively alleviate liver fibrosis injury caused by long-term NaAsO_2 exposure in SD rats.

ALL-548 Assessment of Serum Hyaluronic Acid and Ferritin Levels in Children With Acute Lymphoblastic Leukemia

Serum levels of hyaluronic acid (HA) and ferritin are high in newly diagnosed children with acute lymphoblastic leukemia. To evaluate the level of serum hyaluronic acid and ferritin in patients with ALL at diagnosis and in remission and investigate their impact on disease development and prognosis. A prospective cross-sectional study was conducted in the Central Teaching Hospital of Pediatrics, Baghdad, Iraq from January to October 2020. The study was conducted on hospitalized patients. For each patient, consent was obtained to take peripheral blood (PB) and/or bone marrow (BM) samples, and serum samples were analyzed in a private laboratory. 60 subjects were enrolled in this study, 40 ALL patients as cases (20 patients at diagnosis before starting chemotherapy and 20 patients in remission but still under therapy); and 20 age and sex-matched healthy subjects as controls. Both Band T-ALL subtypes were included. The age was less than 15 years. The patients were randomly collected in relation to gender. Patients on iron supplementation, with liver diseases, and those with other types of malignancy were excluded. The diagnosis of ALL was based on morphological assessments of the stained PB and BM smears according to the standard French-American-British criteria and confirmed by cytochemical stains and flow cytometric immunophenotyping. Patients with complete remission were also evaluated by morphological examination. Serum HA was measured using a commercially available sandwich ELISA kit while serum ferritin was measured by an immunoassay analyzer. Serum HA in newly diagnosed patients with ALL was significantly higher than either patients in remission (P-value 0.022) or controls (P-value 0.001). Both newly diagnosed patients and those in remission had elevated levels of serum ferritin with no significant difference. Serum levels of HA correlated positively with both serum ferritin and LDH (p<0.001). Our data suggest that serum level of hyaluronic acid could have a role in the malignant process of ALL and may serve as a possible marker for aggressiveness. Further studies on larger populations and on patients with relapse and follow-up of patients for a longer period of time are recommended.

DETERMINATION OF HYALURONIC ACID AND N-PEPTIDE OF COLLAGEN TYPE III LEVELS IN SERUM AS PREDICTORS OF THE PERITONEAL ADHESIONS DEVELOPMENT IN CHILDREN

Introduction. Adhesive peritoneal disease (APD) is the most common and formidable complication of abdominalsurgery, which led to adhesive processing occurring in 70 to 90 % of operated patients. It is manifested by lateadhesion intestinal obstruction (LAIO), chronic abdominal pain, constipation and infertility.The aim of the study was to investigate the levels of hyaluronic acid (HA) and N-peptide collagen type III (N-PCIII) in serum to determine the course of APD in children.Material and methods. Serum levels of HA and N-PC type III were determined in 148 children aged 6-17 years (83boys and 65 girls). I group (main) – 38 patients with APD, LAIO treatment with the use solution of natrii hyaluronasand decamethoxine, II comparison group – 35 children with APD, LAIO treatment by traditional methods, III group – 45patients operated on for other acute surgical pathologies of GI tract in which after surgery for 5-10 years no signsof APD were noted. The control group consisted of 30 children operated on inguinal hernias.All parents were given informed voluntary written consent to conduct the research. Statistical processing of theobtained results was performed using Microsoft Office Excel and Statistica 10.0 (StatSoft Inc.).Results. An increase in HA level in the control, main and comparative groups on the 5th day of postoperative periodwas registered by 31,94, 126,96 and 39,60%, respectively, in comparison with the preoperative values; on the 14th daydecrease in HA level was observed in all groups, by 21,24, 32,79 and 25,83%, respectively, in comparison with the 5th day.Determination of the level of N-PC type III in all groups showed an increase in its number on the 5th day,compared with pre-surgery by 64.62, 57.40 and 79.32 %, respectively. On the 14th day the level was 2 times higher inthe main group and 2.86 times higher in the comparison group, compared with the control indicators. This indicatedthe stabilization of connective tissue organization and peritoneal regeneration in the main group and the lack of clearperitoneal regeneration in the comparison group.Conclusions.1. Serum levels of HA and N-PC type III may be markers of the onset and development of APD in children.2. An increase in the level of HA by more than 30%, and N-PC type III by 90 %, compared with control indicators,a year or more after undergoing surgery for APD, LAIO, may indicate a high risk of recurrence and be used as anadditional prognostic indicator.3. Intraoperative use of sodium hyaluronate and decamethoxine in abdominal surgery and the use of localadhesiolysis as anti-adhesive measures help reduce the risk of re-adhesion in children.

Phloridzin Reveals New Treatment Strategies for Liver Fibrosis.

Liver fibrosis is an urgent public health problem which is difficult to resolve. However, various drugs for the treatment of liver fibrosis in clinical practice have their own problems during use. In this study, we used phloridzin to treat hepatic fibrosis in the CCl4-induced C57/BL6N mouse model, which was extracted from lychee core, a traditional Chinese medicine. The therapeutic effect was evaluated by biochemical index detections and ultrasound detection. Furthermore, in order to determine the mechanism of phloridzin in the treatment of liver fibrosis, we performed high-throughput sequencing of mRNA and lncRNA in different groups of liver tissues. The results showed that compared with the model group, the phloridzin-treated groups revealed a significant decrease in collagen deposition and decreased levels of serum alanine aminotransferase, aspartate aminotransferase, laminin, and hyaluronic acid. GO and KEGG pathway enrichment analysis of the differential mRNAs was performed and revealed that phloridzin mainly affects cell ferroptosis. Gene co-expression analysis showed that the target genes of lncRNA were obvious in cell components such as focal adhesions, intercellular adhesion, and cell–substrate junctions and in metabolic pathways such as carbon metabolism. These results showed that phloridizin can effectively treat liver fibrosis, and the mechanism may involve ferroptosis, carbon metabolism, and related changes in biomechanics.

Methods of a New Chronic Pancreatitis and Spontaneous Pancreatic Cancer Mouse Model Using Retrograde Pancreatic Duct Injection of Dibutyltin Dichloride.

The current study aimed to develop a new chronic pancreatitis and spontaneous pancreatic cancer model on C57/BL6 mouse through retrograde pancreatic duct injection of dibutyltin dichloride (DBTC) and explore its basic pathological changes as compared to the previous published chronic pancreatitis model through tail vein injection of DBTC with alcohol drinking. C57/BL6 mice were randomly divided into 3 groups: CG (control group; n = 15), VG (tail vein injection of DBTC (8 mg/kg) with 10% alcohol drinking group; n = 20), and PG (retrograde pancreatic duct injection of DBTC group (1 mg/kg); n = 30). Five mice in each group were sacrificed at a specific time point after the first treatment. The pathological section was observed. The activities of amylase, bilirubin, and hyaluronic acid in serum were determined. The expression of fibronectin, COL1A1, α-SMA, MMP-1, and TIMP-1 in the pancreas was assayed. Severe fibrosis of the pancreas with inflammatory cell infiltration could be observed on day 21 in the PG. In the VG, slight fibrosis of the pancreas with inflammatory cell infiltration was observed on day 28. There were significant differences in serum amylase, bilirubin, and hyaluronic acid levels between the PG and VG. The protein level of COL1A1 and α-SMA significantly increased in the PG. The mRNA expression of TIMP-1 is upregulated and the MMP-1 mRNA level is downregulated in the PG. Finally, typical neoplastic pathological change is significantly obvious in the PG. In conclusion, we established and validated a new chronic pancreatitis (CP) and spontaneous pancreatic cancer mouse model through retrograde injection of DBTC into the pancreatic duct. Previously reported mouse model through tail vein injection of DBTC with alcohol drinking could not cause obvious CP and neoplastic pathological change in mice.

Extracts of Periplaneta americana alleviate hepatic fibrosis by affecting hepatic TGF-β and NF-κB expression in rats with pig serum-induced liver fibrosis.

Liver fibrosis is caused by continuous wound healing responses to various harmful stimuli, including viral infection, drugs, alcohol, and autoimmune liver disease. The purpose of this study was to examine the effects of extracts of Periplaneta americana (EPA) in rats with pig serum-induced liver fibrosis to preliminarily assess the antifibrotic effect of EPA. Seventy rats were randomly divided into 7 groups (10 rats in each group): HC, the healthy control group; FC, the fibrotic control group; TL, low-dose EPA treatment group group; TM, medium-dose EPA group; TH, high-dose EPA treatment group; TC1, Panax notoginseng/Salvia mitiorrhiza treatment control group 1; TC2, colchicine treatment control group 2. TC1 and TC2 were used as the positive control to demonstrate the difference between EPA and the effects of other compounds. The liver fibrosis model was induced by intraperitoneal injection of 0.5 mL pig serum twice a week for 13 weeks in all groups except for the HC group. The hepatic fibrosis model was established at the 7th week, and followingly, the corresponding compounds were administered once a day in all groups for 6 weeks. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity was determined in rat blood serum. We also measured liver fibrosis-related serum markers, including hyaluronic acid (HA), mucin layer (LN), type III pre-collagen (PC-III) and type IV collagen (IV-C). Hematoxylin and eosin (H&E) and Masson stainings were used to assess liver morphology and determine the stage of fibrosis. Immunohistochemistry was used to detect the protein expression of NF-κB, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in rat liver tissue. Compared with that of the HC group, the liver tissue of the FC group presented obvious liver damage and collagen deposition. The serum levels of ALT, AST, HA, LN, PC-III and IV-C and the expression of NF-κB, α-SMA, TGF-β1 and TIMP-1 in the FC group were significantly higher than those in the HC group, the EPA treatment groups, the TC1 group and the TC2 group (P < 0.01). The levels of serum ALT, AST, HA, LN, PC-III and IV-C and the expression of α-SMA, NF-κB, TGF-β1 and TIMP-1 in the TL, TC1 and TC2 groups were significantly higher than those TM and TH groups (P < 0.05). EPA treatment significantly improved liver function, decreased collagen deposition and reversed the pathological changes related to liver fibrosis. We found that EPA could reduce liver inflammation, suppress liver cell degeneration and necrosis, and reduce the formation of liver fibrous tissue. Its mechanism might be associated with inhibiting the expression of TGF-β1, TIMP-1, NF-κB and α-SMA to block signal transduction pathways in the hepatic fibrosis process. Therefore, EPA, as a traditional Chinese medicine, might be potentially used to prevent and treat hepatic fibrosis in the future. However, further more experiments are necessary to verify its effectiveness and possible signaling pathways.