Role of Transcription Factor 7 like 2 and Silent Information Regulator 1 Genes in the Development of Cardiovascular Complications in a Group of Egyptian Patients with Chronic Kidney Disease

BACKGROUND: Sirtuins silent information regulator 1 (SIRT) is histone deacetylases that act as antioxidants and involved in the pathogenesis of cardiovascular diseases (CVD) which are the major complications of chronic kidney disease (CKD). Transcription factor 7-like 2 (TCF7L2) genetic polymorphisms could contribute to the risk of CVD as TCF7L2 proteins regulate vascular remodeling. AIM: We tried to demonstrate the role of genetic polymorphisms: rs7069102 and rs10823108 in SIRT1 gene and rs7903146 in TCF7L2 gene in the development of CVD in CKD Egyptian patients. METHODS: This study included 120 CKD patients (60 with CVD and 60 without CVD) and 60 age and sex-matched healthy subjects as a control group. Routine laboratory investigations were performed and genotyping for candidate single nucleotide polymorphisms was done by Taqman-real-time polymerase chain reaction. RESULTS: The frequency of the C allele of rs7069102 was significantly higher in CKD patients with CVD as compared to the normal control group (p < 0.001) and as compared to CKD patients without CVD (p < 0.001). Percentages of AG and GG genotypes of rs10823108 were significantly higher in CKD patients with CVD as compared to the normal control group (p = 0.002, 0.035, respectively). The frequency of the T allele of rs7903146 was significantly higher in CKD patients with CVD as compared to the normal control group (p < 0.001). CONCLUSION: We found that C allele of rs7069102, GG and AG genotypes of rs10823108 in the SIRT1 gene and T allele of rs7903146 in TCF7L2 gene have a potential role in the pathogenesis and the risk of CVD development in CKD Egyptian patients.

Evaluation of an Ayurvedic preparation-‘Ekangaveera Rasa' for possible metal toxicity: Behavioral, Biochemical and Histopathological Analysis

Ayurveda, an ancient Indian medicinal system, is highly regarded as complementary and alternative medicine in recent years. However, there are reports to show the toxic effects of specific Ayurvedic preparations, which use metals as an ingredient in them. One such medicine is 'Ekangaveera Rasa' This herbo-minero-metallic preparation is used to treat the pain of neurological origin. Therefore, the present study aimed to evaluate the possible alteration caused by Ekangaveera Rasa on the brain, liver, and kidneys by histological, biochemical, and behavioral analysis. For this evaluation, Wistar rats were divided into four groups: Group 1- normal control; group 2, 3 and 4 were treated with Ekangaveera Rasa at doses of 120, 240 and 600 mg/kg bodyweight for 30 days. Behavioral parameters were assessed on the 15th and 30th day by using the passive avoidance test. At the end of the treatment period, blood was collected and subjected to the basophilic stripling and biochemical analysis. Tissues were processed for histopathological evaluation. The histopathological, biochemical, and behavioral analysis did not show any harmful effect, thereby rendering Ekangaveera Rasa nontoxic and further glorifying the healing benefits of Ayurveda.

Effect of Tamarindus indica juice intake on some oxidative stress markers in carbon tetrachloride induced rats

Tamarind tree is a multipurpose tree of which almost every part finds at least some use, either nutritional or medicinal. Due to its pleasant acidic taste and rich aroma, the pulp is widely used for domestic and industrial purpose. A study was carried out to evaluate the effect of Tamarind juice intake in CCl4 induced oxidative stress albino rats. The Proximate, antinutrient, and Phytochemical contents of tamarind juice were analyzed using standard AOAC methods while mineral contents were determined using atomic absorption spectrometry. Oxidative stress markers were also analyzed using colorimetric assay kit. The serum levels of oxidative stress markers were compared between the normal and test groups. Experimental rats were divided into five groups: Normal control group, negative control (CCl4) group, standard drug (Vitamin C) group, tamarind low and high dose group. At the end of the experiment, significant increase in malondialdehyde level and decrease in superoxide dismutase, catalase, reduced glutathione and glutathione Peroxidase activities were recorded in CCl4-exposed rats as compared to normal control group. In the tamarind supplemented groups, the level of MDA along with the activities of SOD, CAT, GSH and GPx were comparable with the normal control rats (p>0.05). Thus, it appears that tamarind juice ameliorate the effect of CCl4; suggesting that consumption of natural compounds with an antioxidant profile may be a preventive alternative to those diseases associated with oxidative stress.

Effects of Serum Metabolites on the Pancreatic Transcriptome in Acute Acalculous Cholecystitis

Background. To provide a basis for the diagnosis and treatment of acalculous biliary pancreatitis, this study investigated the impact of serum metabolites on the pancreatic transcriptome in acute acalculous cholecystitis (AAC). Methods. Fourteen rabbits were randomly divided into two groups (a normal control group of 7 rabbits and an AAC group of 7 rabbits), blood was collected from the 14 rabbits, and metabolomic analysis was performed through 1H NMR. Two pancreatic tissue chips of the AAC group and the normal control group were prepared and sequenced. We utilized the limma package of R software, the DAVID database, the STRING database, Cytoscape software, and the CFinder analysis tool to perform differential expression gene analysis, gene function enrichment analysis, protein interaction network (PPI) construction, and network module mining, and we performed gene enrichment analysis in each module. Results. Serum metabolism analysis showed that in AAC, the metabolism of sugar, lipids, and protein, that is, the three major nutrients, was affected to varying degrees, and levels of serum trimethylamine N-oxide (TMAO) increased. Bioinformatic methods were utilized to identify a total of 183 differentially expressed genes and 3 key genes. Enrichment analysis showed that differentially expressed genes were significantly enriched in cation transport, the inflammatory response, the NF-κB pathway, and the cancer signaling pathway. Conclusion. Metabolomic analysis and functional analysis of 3 key genes demonstrated that abnormal serum metabolites affected the pancreatic transcriptome and induced a sensitive state of inflammation in the pancreas. These metabolites may represent important targets for future research on the pathogenesis, clinical diagnosis, and treatment of noncalculous biliary pancreatitis.

Magnesium isoglycyrrhizinate inhibits airway inflammation in rats with chronic obstructive pulmonary disease

Background Chronic obstructive pulmonary disease (COPD) is a kind of chronic lung diseases with the characteristics of airway remodeling and airflow obstruction. Magnesium isoglycyrrhizinate (MgIG) is an anti-inflammatory glycyrrhizic acid preparation for treating hepatitis. However, whether MgIG can treat other diseases and its action mechanism is still obscure. In this study, we evaluated the anti-inflammatory effect of MgIG in rats with COPD and investigated the underlying mechanisms. Methods Rat model of COPD was constructed by endotracheal-atomized lipopolysaccharide exposure and cigarette smoke induction. Rats were randomly divided into 5 groups: control group, COPD model group, salmeterol fluticasone comparator group, low dose of MgIG group, and high dose of MgIG group. Except for normal control group, the other four groups received sensitization treatment by cigarette smoking and endotracheal-atomization of endotoxin lipopolysaccharide to construct COPD rats model. After model established successfully, the COPD rats in each group received corresponding dose of endotracheal-atomized normal saline, salmeterol fluticasone, and MgIG every day prior to exposure of cigarette smoke from days 30 to 45. Normal control group were treated with normal saline. Finally, All rats were euthanatized. Pulmonary function was measured. Cells in bronchoalveolar lavage fluid were classified, inflammatory factors IL-6 and TNF-α were determined, histopathological analysis was performed by HE staining, and expression of NLRP3 and cleaved caspase-1 in the lung tissue was also determined by Western blotting. Results It showed that MgIG treatment (0.40 or 0.80 mg/kg/day) could recover the weight and the clinical symptoms of rats with COPD, accompanied with lung inflammation infiltration reduction, airway wall attenuation, bronchial mucus secretion reduction. Additionally, MgIG administration reduced inflammatory cells (white blood cells, neutrophils, lymphocytes and monocytes) accumulation in bronchoalveolar lavage fluid and decreased IL-6 and TNF-α production in the serum of COPD rats. Furthermore, MgIG treatment also reduced the expression level of NLRP3 and cleaved caspase-1. Conclusion It indicate that MgIG might be an alternative for COPD treatment, and its mechanism of action might be related to the suppression of NLRP3 inflammasome.

Effect of vitiligo treatment by compound Glycyrrhizin combined with fractional laser and Triamcinolone Acetonide injection on T Lymphocyte subpopulation

Objectives: To discuss the effective mechanism of vitiligo treatment by compound glycyrrhizin combined with fractional laser and triamcinolone acetonide injection. Methods: Forty-two patients with vitiligo vulgaris in the stable phase were classified into combined group (19 cases) and medicine group (23) admitted in dermatology department, Baoding First Central Hospital from January 2017 to July 2018. Both groups took 50mg compound glycyrrhizin orally three times per day, and applied halometasone cream externally once per day. Based on this treatment method, after the combined group adopted fractional laser, triamcinolone acetonide injection encapsulation was used immediately. After the treatment for six months, the curative effect was judged for both groups. Flow cytometry was used to test the changes of T lymphocyte subpopulation in peripheral blood before and after treatment. Meanwhile, immunohistochemical method was adopted to determine CD4+ and CD8+ T lymphocyte expression level. Besides, the normal control group was set up. Results: The efficacy of combined group and medicine group were 73.68% and 56.52% respectively, P<0.05. The comparison of CD3+, CD4+, CD8+ and CD4+/CD8+ T lymphocyte level in serum and skin damage before and after treatment had no statistical significance (P>0.05). Serum CD4+ T cells of vitiligo patients reduced, compared with the normal control group (P<0.05), and CD4+/CD8+ declined (P<0.05). CD4+ and CD8+ T lymphocytes at the skin damage of patients increased, compared with normal control group (P<0.05). Conclusions: Compound glycyrrhizin combined with fractional laser and triamcinolone acetonide injection has good clinical effect in the treatment of vitiligo vulgaris in the stable phase, and its effective mechanism may have nothing to do with T lymphocyte subpopulation. doi: https://doi.org/10.12669/pjms.38.1.4412 How to cite this:Li L, Gao L, Zhao Y. Effect of vitiligo treatment by compound Glycyrrhizin combined with fractional laser and Triamcinolone Acetonide injection on T Lymphocyte subpopulation. Pak J Med Sci. 2022;38(1):---------. doi: https://doi.org/10.12669/pjms.38.1.4412 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Effects of white vinegar on carbohydrate contents in hepatorenal tissues in rats.

White vinegar is mildly acidic with a pH of 2-3 that has long been used as a relish and traditional medication that depends on its concentration. Yet even a small amount of white vinegar in a small concentration may cause serious poisoning. Recently, many sorts of white vinegar have been developed using fundamental sources and technologies to satisfy customer needs. This study was aimed to investigate the effects of white vinegar on carbohydrate contents in hepatorenal tissues in rats. Thirty female rats were used, they were divided into three groups, group 1 was given distilled water as the normal control group, group 2 was given white vinegar with a dose (1 ml/kg (5 %)) and group 3 was given white vinegar with a dose (1 ml/kg (10 %)) for two weeks. PAS stain in all treated tissues showed a decrease in carbohydrate contents when compared with the control group. In conclusion, white vinegar consumption has adverse effects on carbohydrate contents in hepatic and renal tissues in rats, hence the quantity of white vinegar should be discouraged or reduced.

Carotid Intima-Media Thickness and Ankle-Brachial Index and Their Correlation with Coronary Artery Dilatation in Children with Kawasaki Disease

Objective. To investigate the correlation between carotid intima-media thickness (IMT), ankle-brachial index (ABI), and coronary artery dilatation (CAD) in children with Kawasaki disease (KD) and to evaluate the effectiveness of CAD. Methods. A total of 68 children diagnosed with KD from January 2019 to January 2021 in our hospital were included. According to the results of cardiac color Doppler ultrasound, the children with KD were divided into a noncoronary artery dilation group (NCAD), with 41 children with KD who did not have coronary artery lesions, and a coronary artery dilation group (CAD), with 27 children with KD who had coronary artery dilation. 27 healthy children undergoing physical examination in our hospital at the same time were selected as the normal control group. Laboratory index of all subjects was measured individually. The carotid IMT, ABI, and coronary artery diameter of all subjects were measured and compared. Pearson correlation was used to analyze the correlation between carotid IMT, ABI, and the severity of coronary artery disease. The ROC curve was used to evaluate the efficacy of carotid IMT and ABI in predicting coronary artery disease. Results. The ALB of children in the CAD group was lower than that in the NCAD group P < 0.05 . The IMT of carotid artery and the diameter of coronary artery in children of the CAD group and the NCAD group were higher than those of the normal control group, and the IMT of the CAD group was higher than that of the NCAD group. The ABI of children in the CAD group and the NCAD group was lower than that of the normal control group, and the ABI of children in the CAD group was lower than that of the NCAD group P < 0.05 . Correlation analysis showed that carotid artery IMT of children with KD was positively correlated with coronary artery diameter, while ABI was negatively correlated with coronary artery diameter. The AUC of carotid IMT for CAD in children with KD was 0.668 (95% CI: 0.538–0.797), that of ABI for CAD in children with KD was 0.646 (95% CI: 0.513–0.780), and that of the combination of carotid IMT and ABI for CAD was 0.874 (95% CI: 0.785–0.963). Conclusion. The changes of carotid artery IMT and ABI in children with KD have a certain correlation with CAD, and the joint detection of carotid artery IMT and ABI can provide clinical reference value for predicting the degree of coronary artery disease in children with KD.

Pathological Characters and Molecular Pathogenesis of Diabetic Neuropathic Osteoarthropathy Cartilages Damage

Background: Diabetic neuropathic osteoarthropathy (DNOAP) is a rare and easily missed complication for diabetes that leads to increased morbidity and mortality. DNOAP is characterized by progressive destruction of bone and joint, but its pathogenesis remains elusive. We herein aimed to investigate the pathological features and pathogenesis of the cartilages damage in DNOAP patients. Methods: The articular cartilages of 8 patients with DNOAP and 8 normal controls were included. Masson staining and safranine O/fixed green staining (S-O) were used to observe the histopathological characteristics of cartilage, and the ultrastructural changes of chondrocytes were detected by electron microscopy. Chondrocyte were isolated from DNOAP group and control group. The expression of RANKL, OPG, IL-1β, IL-6, TNF-α, Aggrecan protein were evaluated by Western blot. ROS levels were measured using a DCFH-DA probe. The percentage of apoptotic cells was determined by flow cytometry. The chondrocytes were cultured with different glucose concentrations to observe the expression of RANKL and OPG.Results: Compared with the control group, the DNOAP group showed fewer chondrocytes, subchondral bone hyperplasia and structural disorder, and a large number of osteoclasts formed in the subchondral bone area. Moreover, mitochondrial and endoplasmic reticulum swelling were observed in the DNOAP chondrocytes. The chromatin was partially broken and concentrated at the edge of nuclear membrane. The ROS fluorescence intensity of chondrocyte in DNOAP group was higher than that in normal control group (28.1 ± 2.3 VS 11.9 ± 0.7, P < 0.05). The expression of RANKL, TNF-α, IL-1β and IL-6 protein in DNOAP group was higher than that in normal control group, while OPG and Aggrecan protein was lower than that in normal control group (both P < 0.05). Flow cytometry showed that the apoptotic rate of chondrocyte in DNOAP group was higher than that in normal control group (P < 0.05). The RANKL/OPG ratio showed significant upward trend when the concentration of glucose was over than 15mM.Conclusions: DNOAP patients tend to have severe destruction of articular cartilage and collapse of organelle structure including mitochondrion and endoplasm reticulum. Indicators of bone metabolism (RANKL, OPG) and inflammatory cytokines (IL-1β, IL-6 and TNF-α) play an important role in promoting the pathogenesis of DNOAP. The glucose concentration higher than 15mM made the RANKL / OPG ratio changed rapidly.

Analysis of Retinal Capillary Using Optical Coherence Tomographic Angiography of Unilateral Normal Tension Glaucoma

Purpose: The purpose of this study was to analyze retinal capillary parameters using optical coherence tomography angiography (OCTA) of the affected eye and the fellow eye of unilateral normal tension glaucoma (NTG) patients and compare the findings with eyes from a normal control group.Methods: A retrospective cross-sectional study was carried out on patients diagnosed with unilateral NTG (24 affected eyes and 24 fellow eyes each) and normal individuals (29 eyes, the control group). OCTA was used to measure the vascular density (VD) and perfusion density (PD) of the macular area and the peripapillary area.Results: In the superficial capillary plexus, the fellow eye group of unilateral NTG patients showed a decrease in VD of the inner-inferior and PD of the inner-inferior and outer-average peripapillary area, compared with the normal control group (p = 0.008, p < 0.001, and p = 0.001). In the affected NTG eye group, the VD (p = 0.014, p = 0.011, p < 0.001, p < 0.001, and p < 0.001) and PD (p = 0.017, p = 0.023, p < 0.001, p = 0.001, and p < 0.001) of the total, inner-average, inner-inferior, and outer-inferior peripapillary area, and the outer-inferior macular area decreased compared to the fellow eye and normal control group, as well as the VD of the outer-average peripapillary area (p = 0.010). The PD of the outer-average peripapillary area (p = 0.003); the VD (p = 0.041, p = 0.008, p = 0.006) and the PD (p = 0.013, p < 0.001, p = 0.001) of the total, inner-inferior, and outer-average macular area; and the PD of the outer-temporal macular area (p = 0.003) were lower than the normal control group. There was no difference in the VD or PD obtained from the deep capillary plexus of the macular area among the groups.Conclusions: It is useful to observe retinal capillary parameters using OCTA for patients with unilateral NTG.