scholarly journals Detoxification II Prescription Suppresses the Th-17/IL-17 Inflammatory Axis to Improve the Liver Function of ACLF-Rats via Inactivating the P38MAPK Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Qinglan Shi ◽  
Wenjie Bai ◽  
Dewen Mao ◽  
Yueqiao Chen ◽  
Kejing Wang ◽  
...  

Hepatitis is a metabolic system disease which is a serious challenge to the medical and healthcare system of the world. This study attempted to investigate the therapeutic effect and illustrate the regulation pharmacological mechanism of Detoxification II Prescription on ACLF. In this study, the rats were injected with D-galactosamine to establish ACLF-rat models, and the levels of cholinesterase (CHE), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBiL) were measured with the related kits to reflect the liver functions of the rats. The levels of IL-17, IL-6, and IFN-γ in the serums of the rats were detected by qRT-PCR, and the percentages of Th-17 cells in CD4+ cells of the rats were measured by flow cytometry assay. In the results, the increased ALT, AST, TBiL, IL-6, IL-17, IFN-γ, and percentage of Th-17 cells in CD4+ and decreased ALB and CHE were found in the serums of the ACLF-rats, while Detoxification II Prescription could partly reverse those indexes of the ACLF-rats. Moreover, it was also found that Detoxification II Prescription could inhibit the expression of P38MAPK, and P38MAPK downregulation obviously improved the liver function indexes of the ACLF-rats including the levels of ALT, AST, TBiL, IL-6, IL-17, IFN-γ, and percentage of Th-17 cells in CD4+ cells. In conclusion, this study suggested that Detoxification II Prescription could suppress the Th-17/IL-17 inflammatory axis to improve the liver function of ACLF-rats via inhibiting the activity of the P38MAPK pathway.

1967 ◽  
Vol 54 (1) ◽  
pp. 73-84 ◽  
Author(s):  
H. L. Krüskemper ◽  
G. Noell

ABSTRACT In male subjects investigations have been carried out regarding the effect of C1- and C17-methylated androstane derivatives (20 mg per day, orally, two weeks) on liver functions (parameters: activities of GPT, GOT, alkaline phosphatase and cholinesterase in serum; electrophoretic pattern; blood coagulation factors V, VII, X and prothrombin; BSP-retention). In addition to the well known hepatotropic action of 17α-alkylated C-19-steroids a quasi-axial 1α-methyl configuration (in 1α-methylandrost-2-en-17β-ol) definitely increased BSP-retention and several coagulation factors. These steroid effects decreased gradually when a methyl group was introduced in C1 equatorially (1-methylandrost-1-en-17β-ol-3-one) or quasi-equatorially (1β-methylandrost-2-en-17β-ol), the latter compound completely lacking from any influence on parameters of liver function under investigation.


2020 ◽  
Vol 11 (1) ◽  
pp. 27-32
Author(s):  
Wahyu Alfandry Pulungan

Selection of issues regarding the kind of kidney disease as a sample of this study, is the fact that diseases Kidney is an important organ in our body's metabolic system, because the density of activity, we often forget to take care of. Irregular diet, inadequate intake of fiber and mineral water, as well as the consumption of food or drink high calorie instant, unwittingly aggravate the kidneys. Starting from the filtration, reabsorption, to augmentation of nutrients that under to the kidneys via the blood. The purpose of this research is to build an expert system Kidney disease using Visual Basic 6.0 programming language that is capable of providing services to the public and delivery of information related to kidney disease. In this research, data collection is done by using the method of observation, interviews, and literature. From the results of this study indicate that the presence of kidney disease diagnosis expert system in humans can provide significant benefits, among others, the processing of data and consultation process carried out quickly and produce a fairly accurate report, thus making the job more effectively and efficiently. Keywords: Expert System, Disease, Kidney, Human.


Blood ◽  
2001 ◽  
Vol 97 (2) ◽  
pp. 523-527 ◽  
Author(s):  
Reinhard Dummer ◽  
Udo Döbbeling ◽  
Ralf Geertsen ◽  
Jörg Willers ◽  
Günter Burg ◽  
...  

Abstract Cutaneous T-cell lymphomas (CTCL) comprise a heterogeneous group of lymphoproliferative disorders that are characterized by an accumulation of T-lymphocytes in the skin and occasionally in blood known as Sézary syndrome (SS). In most cases the dominant clone displays T-helper 2 cytokines. Because IFN-γ is a natural inhibitor of T-helper 2 cells and IFN-α is frequently used in CTCL, the impact of IFNs on SS-derived purified clonal T-helper 2 cells was studied using anti-Vβ antibodies. Moreover, IFNs are known to mediate virus resistance in normal cells. The isolated clonal CD4+ cells, but not the nonclonal CD4+ cells, appeared resistant to IFN-γ and IFN-α stimulation in terms of human leukocyte antigen up-regulation and MxA induction caused in part by alterations in Stat-1 molecule mRNA and IFNγR1 mRNA transcription. The IFN resistance of the patient-derived clonal cells was then targeted by vesicular stomatitis virus infection after IFN-α priming, resulting in selective viral replication in clonal cells. In contrast, nonclonal cells of the same patient showed IFN-dependent MxA expression, which is a major mediator protein of viral protection. The IFN resistance of the dominant T-helper 2 cells might be important for lymphomagenesis. Interferon signaling deficiencies can be targeted for purging patients' cells in vitro. Furthermore, this approach may allow specific molecular interventions, resulting in the efficient treatment of CTCL and other IFN-resistant neoplasms such as lung cancer.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tsuguru Hayashi ◽  
Tatsuyuki Watanabe ◽  
Michihiko Shibata ◽  
Shinsuke Kumei ◽  
Shinji Oe ◽  
...  

AbstractLiver function is a most important prognostic factor in patients with liver cirrhosis. Also, portal hypertension is a fatal complication of liver cirrhosis and variceal treatment is indispensable. However, changes of liver functions after endoscopic variceal treatments are unknown. The aim of this study was to evaluate prognosis and liver functions after endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL). A total of liver cirrhotic 103 patients who underwent prophylactic EIS and EVL were enrolled. Overall survival rate was higher in EIS group than EVL group (p = 0.03). Multivariate analysis showed that EIS was a negative factor for death (HR: 0.46, 95% confidence interval: 0.24–0.88, p = 0.02). Liver functions were assessed by blood test taken at before and 3 months after treatment. In EIS group, albumin and prothrombin time improved (p < 0.01), leading to improvement of Child–Pugh score, ALBI score and MELD score (p < 0.05). However, these did not improve in EVL group. EIS was a significant factor related to the elevated value of albumin after treatment in linear regression analysis (estimated regression coefficient: 0.17, 95% confidence interval: 0.05–0.29, p = 0.005). These results revealed that EIS could improve liver functions and prognosis.


Author(s):  
Olisekodiaka MJ ◽  
Onuegbu AJ ◽  
Igbeneghu C ◽  
Garuba WO ◽  
Amah UK ◽  
...  

Author(s):  
Kritika Kaushal ◽  
Harvinder Singh ◽  
Anil Kant Thakur

Objective: Swertia chirata has been used in traditional and folklore medicine to treat several ailments such as hepatic disorders. However, the mechanistic and experimental justification to its traditional use is lacking. The present study was aimed to investigate the hepatoprotective potential of S. chirata during hypoxia (HYP)-induced hepatic damage in Wistar rats and to determine the underlying mechanism.Methods: Hydroalcoholic extract of S. chirata was prepared using Soxhlet extraction. Animals were divided into six groups (n=5). Animals in the HYP groups were subjected to HYP for 3 days (10% O2) to induce oxidative stress and hepatic damage. 50 and 100 mg/kg extract treatments were provided orally once daily for 7 days after which animals were sacrificed, and biochemical investigations for oxidative stress, liver function tests, and hepatic histopathology were performed.Results: HYP-induced marked oxidative stress as indicated by the significantly elevated mitochondrial ROS generation, lipid peroxidation, glutathione, and depleted catalase levels. Liver function test indicated hepatic damage as the levels of serum glutamic-oxaloacetic transaminase, serum glutamic pyruvic transaminase, and aspartate transaminase were significantly elevated in HYP animals. S. chirata treatment alleviated oxidative stress and improved liver functions in a dose-dependent manner. Liver histopathology confirmed the marked hepatic damage induced by HYP and revealed that S. chirata efficiently rescued liver from hypoxic damage.Conclusion: Hydroalcoholic extract of S. chirata is a potent hepatoprotective intervention which was associated with its potential to alleviate oxidative stress and improve liver functions. Moreover, it could find clinical application as a safer and alternative remedy for liver ailments.


2014 ◽  
Vol 6 (1) ◽  
pp. e2014025 ◽  
Author(s):  
Ashraf Tawfik Soliman ◽  
Mohamed Yassin ◽  
Fawzia AlYafei ◽  
Lolwa Al-Naimi ◽  
Noora Almarri ◽  
...  

With regular blood transfusion and iron chelation therapy, most patients with thalassemia major (BTM) now survive beyond the third decade of life . Liver disease is becoming an important cause of morbidity and mortality in these patients. Chronic hepatitis and/or severe iron overload are important causes of liver pathology. Iron chelation with desferrioxamine (Desferal)  reduces excessive body iron, but its efficacy is limited by poor compliance and dose related toxicity. The recent use of Deferasirox (Exjade- DFX ), an  oral single dose therapy has improved the compliance to chelation therapy.Aims: To study the long-term liver functions in BMT patients, seronegative for liver infections before versus after DFX therapy in relation to ferritin level and IGF-I level.Methods: Liver function tests including: serum bilirubin, alanine transferase (ALT), aspartate transferase (AST) , albumin, insulin-like growth factor – I (IGF-I) and serum ferritin concentrations were followed every 6 months in 40 patients with BTM, with hepatitis negative screening (checked every year), for at  least   five years of DFO therapy and 4-5 years of DFX therapy .Results: DFX  therapy (20 mg/kg/day)  significantly decreased serum ferritin level in patients with BTM, this was associated with significant decrease in serum ALT, AST, ALP and increase in IGF-I concentrations. Albumin concentrations did not change after DFX treatment. ALT and AST levels were correlated significantly with serum  ferritin concentrations ( r = 0.45 and 0.33 respectively , p < 0.05) . IGF-I concentrations were correlated significantly with serum ALT (r= 0.26, p = 0.05) but not with AST, ALP, bilirubin or albumin levels.The negative correlation between serum ferritin concentrations and ALT suggests that impairment of hepatic function negatively affects IGF-I synthesis in these patients due to iron toxicity, even in the absence of hepatitis.Conclusions: Some impairment of liver function can occur in hepatitis negative BMT patients with iron overload. The use of DFX was associated with mild but significant reduction of ALT, AST and ALP and increase in IGF-I levels. The negative correlation between IGF-I and ALT concentrations suggest that preventing hepatic dysfunction may improve the growth potential in these patients.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3321-3321
Author(s):  
Meixiao Long ◽  
Aaron M. Slaiby ◽  
Adam T. Hagymasi ◽  
Marianne A. Mihalyo ◽  
Alexander C. Lichtler ◽  
...  

Abstract When Th1 effector CD4 cells encounter tolerizing antigen in vivo their capacity to express the effector cytokines IFN-γ and TNF-α is lost more rapidly than non-effector functions such as IL-2 production and proliferation. To localize the relevant intracellular signaling defects, cytokine expression was compared following restimulation with antigen vs agents that bypass TCR-proximal signaling. IFN-γ and TNF-α expression were both partially rescued when TCR-proximal signaling was bypassed, indicating that both TCR-proximal and distal signaling defects impair the expression of these two effector cytokines. In contrast, bypassing TCR-proximal signaling fully rescued IL-2 expression. T-bet, a transcription and chromatin remodeling factor that is required to direct the differentiation of naive CD4 cells into IFN-γ-expressing Th1 effectors, was partially down-modulated in tolerized Th1 effectors. Enforcing T-bet expression during tolerization selectively rescued the ability to express IFN-γ, but not TNF-α. Conversely, expression of a dominant-negative T-bet in Th1 effectors selectively impaired the ability to express IFN-γ, but not TNF-α. Analysis of histone acetylation at the IFN-γ promoter further suggests that down-modulation of T-bet expression during Th1 effector CD4 cell tolerization does not impair IFN γ expression potential through alterations in chromatin structure.


2000 ◽  
Vol 68 (6) ◽  
pp. 3574-3580 ◽  
Author(s):  
Amanda E. Millar ◽  
Stuart J. Kahn

ABSTRACT Trypanosoma cruzi currently infects 18 million people, and 30% of those infected develop a chronic inflammatory process that causes significant morbidity or mortality. The major histocompatibility complex class II (MHC-II)-restricted T-cell response is critical to the control of the infection and to the ensuing inflammatory pathology. The specific epitopes or major antigens of this response have not been identified. The parasite simultaneously expresses variant members of the trans-sialidase superfamily. To begin to analyze the MHC-II response to these variant proteins, the response to a single surface protein, SA85-1.1, was initiated. These studies have demonstrated that a biased gamma interferon (IFN-γ) response to the SA85-1.1 protein develops during T. cruzi infection. In addition, adoptive transfer of a CD4 clone that recognizes an SA85-1.1 epitope, named epitope 1, and immunization with a peptide encoding epitope 1 were protective and suggested that epitope 1 may be immunodominant. In this report IFN-γ intracellular staining demonstrated that splenocytes from acutely and chronically infected mice, incubated with SA85-1.1 protein or peptides that encode epitope 1, result in IFN-γ synthesis by 4 to 6% of the splenic CD4 cells. These data indicate that during T. cruzi infection epitope 1 is a major epitope and that 4 to 6% of the CD4 cells are stimulated by a single trans-sialidase superfamily epitope and suggest that a combination of trans-sialidase superfamily proteins combines to stimulate a majority of CD4 cells. These data suggest that during T. cruzi infection the CD4 response to thetrans-sialidase superfamily is critical to the protective response and to the ensuing chronic inflammatory pathology.


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