scholarly journals Huoxue Jiedu Huayu Formula Alleviates Cell Pyroptosis in Contralateral Kidneys of 6-Month-Old UUO Rats through the NLRP3/Caspase-1/IL-1β Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Xuelian Ma ◽  
Panpan Qiang ◽  
Gege Chen ◽  
Zheng Wang ◽  
Xiangting Wang ◽  
...  
Keyword(s):  
Sham Group ◽  
Unilateral Nephrectomy ◽  
Oral Drug ◽  
Protective Effects ◽  
Caspase 1 ◽  
Essentially Normal ◽  
Formula Group ◽  
Group A ◽  
And Function ◽  
Excessive Activation

Objectives. To study the protective effects and mechanisms of Huoxue Jiedu Huayu formula on cell pyroptosis through the NLRP3/caspase-1/IL-1β pathway in contralateral kidneys in 6-month-old unilateral ureteral obstruction (UUO) rats. Methods. Wistar rats were randomly assigned to 5 groups: a Sham group, a unilateral nephrectomy group (UNX group), a UUO group, a UUO treated with spironolactone group (Spi group), and a UUO treated with Huoxue Jiedu Huayu formula group (HJHF group). After 6 months of oral drug intervention, blood and contralateral kidneys were collected for research. Results. The morphology and function of the contralateral kidneys were essentially normal after unilateral nephrectomy. HJHF obviously decreased serum creatinine, urea, and inflammatory lesions and depressed cell pyroptosis based on the NLRP3/caspase-1/IL-1β pathway. Moreover, spironolactone, a mineralocorticoid receptor (MR) blocker, suppressed cell pyroptosis through SGK-1 and NF-кB. Conclusion. HJHF and spirolactone inhibited excessive activation of MR and then reduced cell pyroptosis, which was dependent on the NLRP3/caspase-1/IL-1β pathway, to protect the contralateral kidneys of 6-month-old UUO rats.

An Efficacy and Safety Study of Remogliflozin in Obese Indian Type 2 Diabetes Mellitus Patients Who Were Inadequately Controlled on Insulin glargine plus other oral hypoglycemic agents

2020 ◽  
Vol 17 ◽  
Author(s):  
Anand Shankar
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Glargine ◽  
Therapy Group ◽  
Insulin Dose ◽  
Blood Glucose Control ◽  
Hypoglycemic Agents ◽  
Oral Drug ◽  
Group A ◽  
Group B

Aim & Objective: The objective of this retrospective study was to investigate the efficacy of adding remogliflozin to current insulin glargine plus two oral drug i.e. metformin and teneligliptin therapy in poorly controlled Indian type 2 diabetes. Material and Methods: 173 study participants were initially selected from patient database who continued on their insulin glargine or received an increased dose of insulin glargine along with other OHA based therapy (Group A) and 187 were selected who had received remogliflozin (100 mg BD) (Group B) in addition to insulin glargine along with other OHA based therapy. Glycated haemoglobin (HbA1c), total daily insulin dose, body weight, and the number of hypoglycemic events were recorded at weeks 0, 12 and 24. Result: During the study, mean values of HbA1c, FBG and P2BG were significantly reduced in both groups. Insulin requirements decreased from 45.8 ± 16.7 IU/day to 38.5 ± 13.5 IU/day (P < 0.001) and at week 24 even further decreased to 29.5 ± 14.5 IU/Day . Twenty three patients in group B were able to cease insulin treatment altogether after 24 week treatment. It has been observed to attain tight blood glucose control we need to increase insulin dose in group A from 45.5 ± 16.5 IU/Day to 51.5 ± 14.5 at week 12 (P<0.01) and which further increased to 53.8 ± 12.8 IU/Day at week 24 (P<0.01). Adding remogliflozin showed significant effect on blood pressure (P < 0.001) and weight reduction (P < 0.001). It has been observed that 38% patients has achieves targeted HbA1c (≤7%) in group B where it was 22% in group A. Conclusion: Results demonstrate that in uncontrolled T2DM patients remogliflozin 100 mg BD can successfully lay a foundation for prolonged good glycemic control. Early addition of remogliflozin with insulin glargine plus OHAs may be an alternative compare to intensive up titration of insulin daily dose in people with uncontrolled T2DM. Clinical Trial Registration Number: A 2358

Glycine and L-Arginine supplementation ameliorates gastro-duodenal toxicity in a rat model of NSAID (Diclofenac)-gastroenteropathy via inhibition of oxidative stress

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Akinleye Stephen Akinrinde ◽  
Halimot Olawalarami Hameed
Keyword(s):  
Oxidative Stress ◽  
Total Protein ◽  
Therapeutic Index ◽  
Control Treatment ◽  
Control Group ◽  
Protective Effects ◽  
Serum Total Protein ◽  
Significant Amelioration ◽  
Group A ◽  
Group B

Abstract Objectives This study examined the possible protective roles of exogenous glycine (Gly) and L-Arginine (l-Arg) against Diclofenac (DIC)-induced gastro-duodenal damage in rats. Methods Rats were divided into Group A (control), Group B (DIC group) and Groups C–F which were pre-treated for five days with Gly1 (250 mg/kg), Gly2 (500 mg/kg), l-Arg1 (200 mg/kg) and l-Arg2 (400 mg/kg), respectively, before co-treatment with DIC for another three days. Hematological, biochemical and histopathological analyses were then carried out. Results DIC produced significant (p<0.05) reduction in PCV (13.82%), Hb (46.58%), RBC (30.53%), serum total protein (32.72%), albumin (28.44%) and globulin (38.01%) along with significant (p<0.05) elevation of serum MPO activity (83.30%), when compared with control. In addition, DIC increased gastric H2O2 and MDA levels by 33.93 and 48.59%, respectively, while the duodenal levels of the same parameters increased by 19.43 and 85.56%, respectively. Moreover, SOD, GPx and GST activities in the DIC group were significantly (p<0.05) reduced in the stomach (21.12, 24.35 and 51.28%, respectively) and duodenum (30.59, 16.35 and 37.90%, respectively), compared to control. Treatment with Gly and l-Arg resulted in significant amelioration of the DIC-induced alterations although l-Arg produced better amelioration of RBC (29.78%), total protein (10.12%), albumin (9.93%) and MPO (65.01%), compared to the DIC group. The protective effects of both amino acids against oxidative stress parameters and histological lesions were largely similar. Conclusions The data from this study suggest that Gly or l-Arg prevented DIC-induced gastro-duodenal toxicity and might, therefore be useful in improving the therapeutic index of DIC.

The Role of the CX3CL1-CX3CR1 Axis in Renal Disease

2021 ◽  
Author(s):  
Diana Hamdan ◽  
Lisa A. Robinson
Keyword(s):  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Transmembrane Protein ◽  
Soluble Form ◽  
Protective Effects ◽  
Chronic Kidney Diseases ◽  
The Family ◽  
Soluble Species ◽  
And Function

Excessive infiltration of immune cells into the kidney is a key feature of acute and chronic kidney diseases. The family of chemokines are key drivers of this process. CX3CL1 (fractalkine) is one of two unique chemokines synthesized as a transmembrane protein which undergoes proteolytic cleavage to generate a soluble species. Through interacting with its cognate receptor, CX3CR1, CX3CL1 was originally shown to act as a conventional chemoattractant in the soluble form, and as an adhesion molecule in the transmembrane form. Since then, other functions of CX3CL1 beyond leukocyte recruitment have been described, including cell survival, immunosurveillance, and cell-mediated cytotoxicity. This review summarizes diverse roles of CX3CL1 in kidney disease and potential uses as a therapeutic target and novel biomarker. As the CX3CL1-CX3CR1 axis has been shown to contribute to both detrimental and protective effects in various kidney diseases, a thorough understanding of how the expression and function of CX3CL1 are regulated is needed to unlock its therapeutic potential.

Abstract 119: Protective Effects of Chloroquine on Ischemic and Nutrient Depleted Muscle are Mediated by HMGB1 and Caspase-1

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Ulka Sachdev ◽  
Xiangdong Cui ◽  
Qian Sun ◽  
Edith Tzeng ◽  
Alex Chen ◽  
...  
Keyword(s):  
Culture Media ◽  
Statistical Significance ◽  
High Mobility ◽  
Maximal Activity ◽  
Arterial Disease ◽  
Protective Effects ◽  
Artery Ligation ◽  
Beneficial Effects ◽  
Caspase 1 ◽  
Ldh Activity

Introduction: Millions of Americans are at risk for amputation from severe peripheral arterial disease (PAD) when surgery is not possible. Pro-regenerative and angiogenic agents may improve outcome in that setting. Chloroquine (CQ) promotes wound healing in scleroderma but has not been tested in PAD. CQ promotes healing of ischemic muscle, increases muscle high mobility group box 1 (HMGB1), an inflammatory, pro-angiogenic protein, and activates caspase-1 in myoblasts. We hypothesize that HMGB1 mediates protective effects of CQ and is regulated by caspase-1 in muscle. Controlled rather than indiscriminate release of HMGB1 from damaged muscle may be protective during ischemia. Methods: C2C12 myoblasts in low serum were treated with CQ (0-50μM) ± Ac-YVAD-cmk (10 μg/ml), a caspase-1 inhibitor. HMGB1 release in supernatants was measured using ELISA. Cytotoxicity was assessed by comparing spontaneous lactate dehydrogenase (LDH) activity in culture media from control, treated and maximally lysed cells. CQ (50μg/ml) or placebo treated wild-type and inducible HMGB1 knockout (iHMGB1KO) mice underwent unilateral femoral artery ligation (FAL). Laser Doppler perfusion imaging (LDPI) before and 1,7,14 and 21d after FAL was reported as % improvement over time. ANOVA was used to assess statistical significance among groups. Results: CQ (5-10uM) attenuated spontaneous LDH leak after 12h from serum-depleted myoblasts (p <0.01, N=3), and modestly increased HMGB1 release (p <0.001, N=3). Ac-YVAD-cmk reversed the cytoprotective effects of CQ, significantly raising both LDH activity to 55% of maximal activity and HMGB1 in the supernatant. Compared to d1 post FAL, CQ improved perfusion recovery in WT mice by 300-800% over 21 days (p<0.03, N=7/group), but not in iHMGB1KO mice. Conclusion: We present the novel finding that in nutrient-depleted myoblasts, caspase-1 mediates the survival benefits of CQ and regulates HMGB1 release. In turn, HMGB1 is critical for CQ’s beneficial effects on perfusion after FAL, another stress condition. Regulated HMGB1 release may be immunomodulatory, regenerative and modifiable with drugs like CQ. Altering survival and inflammatory pathways through CQ may present a novel therapeutic strategy in PAD.

scholarly journals Dexrazoxane preferentially mitigates doxorubicin cardiotoxicity in female children with sarcoma

Open Heart ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. e001025 ◽  
Author(s):  
Hari K Narayan ◽  
Mary E Putt ◽  
Nikitha Kosaraju ◽  
Alejandro Paz ◽  
Shivani Bhatt ◽  
...  
Keyword(s):  
Circumferential Strain ◽  
Wall Stress ◽  
Left Ventricular ◽  
High Dose ◽  
Protective Effects ◽  
Cavity Size ◽  
Linear Regression Models ◽  
Cardioprotective Effects ◽  
And Function

ObjectiveWe sought to determine how sex and dexrazoxane therapy influence cardiac remodelling in children with sarcoma receiving high-dose doxorubicin.MethodsIn a retrospective cohort of 85 children with sarcoma receiving high-dose doxorubicin, echocardiography measures prior to, early after (within 6 months of doxorubicin completion) and 1 – 2 years after doxorubicin completion were quantified. At each follow-up visit, multivariable, propensity-adjusted linear regression models evaluated dexrazoxane’s effects on changes in left ventricular (LV) shortening fraction (SF), structure, strain and wall stress for subgroups divided by sex. Likelihood ratio tests assessed the interaction between sex and dexrazoxane in determining these changes.ResultsEarly after doxorubicin completion, males not treated with dexrazoxane (n = 15) developed increased cavity size and diminished circumferential strain; females (n = 8) developed diminished SF and strain indices, and increased cavity size and wall stress. With dexrazoxane, males (n = 33) demonstrated less deterioration in circumferential strain by 3.4% (95% CI 0.01 to 6.8), and females (n = 29) demonstrated less reduction in SF by 5.7% (95% CI 2.1 to 9.3), and had mitigation of increases in cavity size and wall stress. In interaction analyses, females had greater protection with dexrazoxane with regard to SF (p = 0.019) and cavity size in diastole (p = 0.002) and systole (p ≤ 0.001). These findings largely persisted 1 – 2 years after doxorubicin therapy.ConclusionsEarly, sustained alterations in LV structure and function occur in children with sarcoma after high-dose doxorubicin, with adverse changes and protective effects of dexrazoxane more pronounced in females as compared with males. Dexrazoxane may have sex-specific cardioprotective effects.

scholarly journals Effects of Ovariectomy on Skeletal Muscle Structure and Function in Young Female Rats: Protective Effects of the Flavanol (−)‐Epicatechin

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Viridiana Navarrrete ◽  
Marcos Ayala ◽  
Antonio Rodriguez ◽  
Francisco Villarreal ◽  
Israel Ramirez-Sanchez
Keyword(s):  
Skeletal Muscle ◽  
Young Female ◽  
Structure And Function ◽  
Female Rats ◽  
Protective Effects ◽  
Muscle Structure ◽  
And Function

scholarly journals Effects of Ozone on Hippocampus BDNF and Fos Expressions in Rats with Chronic Compression of Dorsal Root Ganglia

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Lingling Zhu ◽  
Yanxiu Wang ◽  
Xiaowen Lin ◽  
Xu Zhao ◽  
Zhi jian Fu
Keyword(s):  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Sham Group ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Expression Levels ◽  
Fos Protein ◽  
Before And After ◽  
Formula Group ◽  
Fos Expression

The effects of ozone on hippocampal expression levels of brain-derived neurotrophic factor (BDNF) and c-fos protein (Fos) were evaluated in rats with chronic compression of dorsal root ganglia (CCD). Forty-eight adult female Sprague-Dawley rats were randomly divided into the following 4 groups ( n = 12 ): sham operation (sham group), CCD group, CCD with 20 μg/ml of ozone ( CCD + A O 3 group), and CCD with 40 μg/ml of ozone ( CCD + B O 3 group). Except the sham group, unilateral L5 dorsal root ganglion (DRG) compression was performed on all other groups. On days 1, 2, and 4 after the operation, the CCD + A O 3 and CCD + B O 3 groups were injected with 100 μl of ozone with concentrations of 20 and 40 μg/ml, respectively. Thermal withdrawal latencies (TWLs) and mechanical withdrawal thresholds (MWTs) were measured at various time points before and after the operation. BDNF and Fos expressions were examined in the extracted hippocampi using immunohistochemistry. The TWLs and MWTs of CCD model rats that received ozone were lower with decreased BDNF and increased Fos expression levels, on day 21 after the operation, compared to those of the sham group ( P < 0.05 ). The TWLs and MWTs of the CCD + A O 3 and CCD + B O 3 groups were higher with increased BDNF and decreased Fos expression levels, on day 21 after the operation, compared to those of the CCD group ( P < 0.05 ). The TWLs were longer and the MWTs were higher in the CCD + B O 3 group at each time point with increased BDNF and decreased Fos expression levels, on day 21 after the operation, compared to those of the CCD + A O 3 group ( P < 0.05 ). Our results revealed that ozone can relieve the neuropathic pain caused by the pathological neuralgia resulting from DRG compression in rats. The mechanism of action for ozone is likely associated with changes in BDNF and Fos expression levels in the hippocampus.

scholarly journals Protective effect of LIF-huMSCs on the retina of diabetic model rats

2021 ◽  
Vol 14 (10) ◽  
pp. 1508-1517
Author(s):  
Shan-Na Chen ◽  
◽  
Ying-Xue Ma ◽  
Song Chen ◽  
Guang-Hui He ◽  
...  
Keyword(s):  
Diabetic Rats ◽  
Control Group ◽  
Diabetic Model ◽  
Group A ◽  
Retinal Structure ◽  
Hs Crp ◽  
Group B ◽  
And Function ◽  
Group D ◽  
Control Group Group

AIM: To investigate the protective effect of human umbilical cord mesenchymal stem cells (hUCMSCs) modified by the LIF gene on the retinal function of diabetic model rats and preliminarily explore the possible mechanism. METHODS: A stably transfected cell line of hUCMSCs overexpressing leukemia inhibitory factor (LIF) was constructed. Overexpression was verified by fluorescent quantitative polymerase chain reaction (qPCR). Forty-eight adult Sprague-Dawley rats were randomly divided into a normal control group (group A), streptozotocin-induced diabetic control group (group B), diabetic rats at 3mo injected with empty vector-transfected hUCMSCs (group C) or injected with LIF-hUCMSCs (group D). Four weeks after the intravitreal injection, analyses in all groups included retinal function using flash electroretinogram (F-ERG), retinal blood vessel examination of retinal flat mounts perfused with fluorescein isothiocyanate-dextran (FITC-dextran), and retinal structure examination of sections using hematoxylin and eosin staining. Expression levels of adiponectin (APN), high-sensitivity C-reactive protein (hs-CRP), and neurotrophin-4 (NT-4) in each group was detected using immunohistochemistry, PCR, Western blotting, and ELISA, respectively. RESULTS: A stable transgenic cell line of LIF-hUCMSCs was constructed. F-ERG and FITC-dextran examinations revealed no abnormalities of retinal structure and function in group A, severe damage of the retinal blood vessels and function in group B, and improved retinal structure and function in group C and especially group D. qPCR, ELISA, and Western blot analyses revealed progressively higher APN and NT-4 expression levels in groups B, C, and D than in group A. hs-CRP expression was significantly higher in group B than in groups A, C, and D, and was significantly higher in group C than in group D (P<0.05). CONCLUSION: LIF-hUCMSCs protect the retina of diabetic rats by upregulating APN and NT-4 expression and downregulating hs-CRP expression in the retina.

scholarly journals Exendin-4 improves neuron protection and functional recovery in experimental spinal cord injury in rats through regulating PCBP2 expression

2020 ◽  
Author(s):  
Huaichao Luo ◽  
Qingwei Wang ◽  
Lei Wang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Apoptosis ◽  
Sham Group ◽  
Sham Operation ◽  
Therapeutic Effects ◽  
Rat Models ◽  
Apoptosis Rate ◽  
Cord Injury ◽  
Group A

AbstractAimsIn the present research, we assessed the therapeutic effects of Exendin-4 (Ex-4) on rat models with spinal cord injury (SCI).Materials and methods36 male Sprague–Dawley rats were randomly allocated into three groups, including sham operation group, SCI group and SCI+Ex-4 group (Ex-4 treatment (10 µg/rat) after SCI, i.p.). In the SCI group, a laminectomy was performed at the T10 vertebrae, followed by weight-drop contusion of the spinal cord. In the sham group, a laminectomy was carried out without SCI contusion.Key findingsOur results showed that Basso-Beattie-Bresnahan scale scores were significantly decreased after SCI, and were obviously improved in SCI rats with Ex-4 administration. Additionally, the water content of spinal cord in SCI group was dramatically increased than that in sham group, and after Ex-4 treatment, degree of edema of spinal cord was remarkably reduced. And also, concentration levels of inflammatory cytokines (IL-1α, IL-1β, IL-6 and TNF-α) in the spinal cord were significantly elevated after SCI, and were remarkably reduced in SCI rats with Ex-4 administration. Subsequently, cell apoptosis rate in the injured spinal cord was significantly increased, and after Ex-4 treatment, cell apoptosis rate was remarkably decreased. We also revealed that levels of PCBP2 mRNA and protein were significantly up-regulated after SCI, and were dramatically dropped in SCI rats with Ex-4 administration.SignificanceTake altogether, our findings disclosed that Ex-4 plays a role in promoting neurological function recovery and inhibiting neuronal apoptosis through effecting PCBP2 expression in SCI rat models.

scholarly journals Ameliorate Effects of Li-Fu Formula on IL-6-Mediated Cardiac Hypertrophy in Hamsters Fed with a Hyper-Cholesterol Diet

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Yi-Chang Cheng ◽  
Chieh-His Wu ◽  
Wei-Wen Kuo ◽  
James A. Lin ◽  
Hsueh-Fang Wang ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Cardiac Hypertrophy ◽  
Natriuretic Peptide ◽  
Heart Weight ◽  
Signal Molecules ◽  
Histopathological Analysis ◽  
Protective Effects ◽  
Protein Levels ◽  
Formula Group ◽  
Whole Heart

Hypercholesterolemia diets are considered as major sources to cause cardiac hypertrophy. This study intends to evaluate the effects of Li-Fu formula on cardiac hypertrophy induced by hypercholesterolemia diet. Twenty-four male Golden Syrian hamsters were randomly divided into control, cholesterol and Li-Fu formula groups and fed with different experimental diets for 2 months. Histopathological analysis and western blotting were performed to measure the myocardial architecture, and various cardiac hypertrophy-associated molecules in the excised left ventricle from hamsters. The ratios of whole heart weight/body weight (BW) and left ventricle weight/BW were significantly higher in the cholesterol group but significantly lower in the Li-Fu formula group. The protein levels of both atrial natriuretic peptide and brain natriuretic peptide were significantly increased in the cholesterol group but significantly reduced in the Li-Fu formula group. Additionally, significantly increased interleukin-6, STAT3, MEK5, p-ERK5 and non-cardiomyocyte proliferate signal molecules such as p-MEK and p-ERK, were detected in the cholesterol group but significantly reduced in the Li-Fu formula group. Notably, no significant variations of inflammatory signaling molecules, including p-P38 and p-JNK, were detected in all groups. Our experimental results demonstrated the significant reductions of cardiac hypertrophy and related eccentric hypertrophy signaling, non-cardiomyocyte proliferate signaling in the excised left ventricle of hamsters from the Li-Fu formula. We suggested the protective effects of Li-Fu formula on cardiac hypertrophy that may be useful in prevention or treatment of hypertrophy-associated cardiovascular diseases.

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