Avicenna Journal of Medical Biochemistry
Volume:10 Issue: 2, Dec 2022

Marker gene polymorphisms linked with the renin-angiotensin-aldosterone system (RAAS) have been broadly studied in diabetic nephropathy (DN) patients considering that RAAS is a potential drug target to slow down kidney disease progression.

The aim of the present study was to determine the link between M235T and T174M variants of angiotensinogen (AGT) gene and DN.

A total of 93 patients with DN, mean age of 56 ± 8 years, systolic blood pressure (SBP) of 141 ± 14, and diastolic blood pressure (DBP) of 84 ± 7 mm Hg (mean ± SD) were investigated, among whom 59 patients had a family history of type 2 diabetes mellitus. A total of 96 healthy subjects served as the control group with no family history of diabetic nephropathy (FHDN) and type 2 diabetes mellitus, a mean age of 47 ± 10 years, SBP of 126 ± 11, and DBP of 76 ± 6 mm Hg. PCR–restriction fragment length polymorphism was employed for genotyping M235T and T174M molecular variants.

Genotype frequencies of the variants M235T (χ2 = 2.038, P = 0.361) and T174M (χ2 = 2.952, P = 0.229) did not show any statistically significant association with type 2 diabetic nephropathy (T2DN) compared to the control. Based on FHDN and family history of diabetes mellitus (FHDM), the frequency of genotypes of M235T marker (P = 0.360) in FHDN, and (P = 0.886) FHDM; T174M marker (P = 0.641) in FHDN, and (P = 0.425) FHDM also did not show any statistically significant association with T2DN compared to the controls.

M235T and T174M variants were not associated with DN in a Bangladeshi population.

There is an increasing prevalence of type 2 diabetes mellitus (T2DM) worldwide. The deficiency of vitamin D is a worldwide health problem that can increase susceptibility to T2DM. Cytochrome P450 family 27 subfamily B member 1 (CYP27B1) encodes the enzyme 1α-hydroxylase in the kidney, which converts 25 (OH)-D3 to 1,25 (OH)2-D3. The CYP27B1 rs10877012 G/T polymorphism is located in the gene promoter and can influence vitamin D3 level.

This study aimed to investigate the relationship between CYP27B1 gene polymorphism and the 25 (OH)-D3 serum level and the risk of T2DM. Additionally, the effect of 25 (OH)-D3 level on metabolic parameters was investigated.

We investigated 310 individuals including 205 T2DM patients and 105 healthy subjects from the city of AL-Sulaymaniyah, Kurdistan of Iraq. The CYP27B1 gene variants were identified by the polymerase chain reaction followed by digestion with HinfI restriction enzyme.

The mean level of 25 (OH)-D3 was 18.4 ± 8.5 ng/mL in T2DM patients and 24.1 ± 9.3 ng/mL in healthy controls (P < 0.001). Significantly higher body mass index (BMI), HbA1c level, and fasting blood sugar concentration were detected in individuals with vitamin D insufficiency (P = 0.009, P = 0.001, and P = 0.01, respectively) and vitamin D deficiency (P = 0.025, P < 0.001, and P < 0.001, respectively) compared to those with a sufficient level of vitamin D. The T allele frequency of CYP27B1 was 38.1% in controls and 40.2% in patients (P = 0.6). In the presence of the GT genotype, a significantly lower level of 25 (OH)-D3 was obtained compared to the GG genotype (P = 0.02) among the patients.

We found that the CYP27B1 rs10877012 polymorphism was not a risk factor for T2DM but it affected the level of 25 (OH)-D3 in diabetic patients and vitamin D deficiency and insufficiency increased the values of BMI, HbA1c, and FBS as the metabolic parameters involved in the development of T2DM.

Obesity is defined as excessive fat accumulation in the adipose tissue and peripheral organs. The Kelch-like ECH-associated protein 1 (Keap1) is involved in cellular protection in obesity.

The objectives of this study were to detect the association of Keap1 rs11085735 variants with the risk of obesity in relation to anthropometric parameters and lipid profile in a population from the Kurdistan of Iraq.

A total of 265 volunteers (134 females and 131 males) were randomly selected. According to the body mass index (BMI), individuals were divided into subjects with normal BMI (131 healthy individuals) and obese subjects (134 obese volunteers). Anthropometry and lipid profile parameters were measured in these volunteers and Keap1 rs11085735 variants were identified by the polymerase chain reaction (PCR) followed by digestion with HinfI restriction enzyme.

Triglycerides and low-density lipoprotein cholesterol (LDL-C) serum levels were significantly higher (P < 0.001) in the obese group compared to the control group. The serum level of high-density lipoprotein cholesterol (HDL-C) was significantly lower (P = 0.02) in the obese individuals than in the controls. Moreover, the waist, hip, and wrist circumferences and the waist to hip ratio in obese individuals were significantly higher than in controls (P < 0.001). The frequency of Keap1 AA genotype was 1.5% in the obese group and 0% in the controls (P = 0.36). The frequency of A allele was 4.9% and 3.1% in obese subjects and controls, respectively (P = 0.28). Considering all individuals, carriers of AA genotype of Keap1 had significantly higher BMI and waist and hip circumferences compared to the carriers of AC and CC genotypes.

The present study found abnormal lipid profile among obese individuals compared to individuals with normal BMI. Our findings indicated that the presence of Keap1 polymorphism influenced the anthropometric parameters, and the carriers of AA genotype of Keap1 had significantly higher BMI and waist and hip circumferences compared to the carriers of AC and CC genotypes.

The potential role of exercise in physiological cardiac hypertrophy is rooted in both hormonal and genetic components.

The aim of this study was to determine the impact of resistance exercise on the expression of PI3K and AKT1 in cardiac tissue of type 2 diabetes (T2D) rats and their physiological cardiac hypertrophy.

First, 21 male Wistar rats (220 ± 20 g) were obese with 6-week high-fat diet (HFD) and were randomly assigned into non-diabetes, control T2D, and exercise diabetes groups. After inducing obesity, T2D was induced by intraperitoneal injection of streptozotocin (25 mg/kg) for diabetes groups. Rats in the exercise group completed a 6-week resistance exercise program, 5 sessions per week. PI3K/AKT1 expression and the weight ratio of left ventricular to heart, heart to body, and left ventricular to body were compared by analysis of variance (ANOVA) between groups.

In response to the induction of diabetes, the expression of PI3K/AKT1 in heart tissue decreased significantly compared to that of non-diabetic rats (P = 0.001 and P = 0.001, respectively). Further, resistance training led to a significant increase in PI3K expression (P = 0.028) and AKT1 (P = 0.032) and the weight ratio of left ventricular to heart (P = 0.001), heart to the body (P = 0.001), and left ventricular to the body (P = 0.001) compared to control diabetic rats.

Resistance training is associated with physiological cardiac hypertrophy in diabetic rats, and this improvement may be attributed to the PI3K/AKT1 signaling pathway.

There are many articles in the literature about the importance of 25-(OH) vitamin D3 in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases. However, there is no consensus on 25-(OH) vitamin D3 to predict the prognosis of SARS-CoV-2 cases. Additionally, phosphorus, which has an important role in the cytokine storm, contributes to poor prognosis in SARS-CoV-2 cases.

This study aimed to examine phosphorus and 25-(OH) vitamin D3 levels to predict the prognosis of COVID-19.

A total of 230 SARS-CoV-2 cases and 230 healthy people were included in this study. ROC curve analysis was performed for combined evaluation of phosphorus and 25-(OH) vitamin D3 levels.

In the ROC curve analysis, the area under curve (AUC) was 0.9282, the sensitivity was 92.70%, and the specificity was 92.80%. Phosphorus and 25-(OH) vitamin D3 levels showed negative correlations with procalcitonin, ferritin, D-dimer, C-reactive protein, neutrophil-lymphocyte ratio, and monocytelymphocyte ratio.

Low phosphorus and 25-(OH) vitamin D3 levels may be indicators for poor prognosis in SARS-CoV-2 cases. Conversely, normal phosphorus and 25-(OH) vitamin D3 levels may be indicators for a good prognosis in SARS-CoV-2 cases.

Paraquat (PQ) is one of the most important herbicides used in agriculture.

This study was conducted to compare the preventive effect of vitamin D (Vit D) and N-acetylcysteine (NAC) against kidney injury in rats versus the promotive effect of PQ.

In this study, rats were divided into six groups. The control group (group 1) received normal saline, Vit D group (group 2) received intraperitoneal (IP) injections of + Vit D (2 μg/kg), NAC group (group 3) received NAC (6.25 mg/kg, IP), PQ group (group 4) received PQ (5 mg/kg/d, IP), PQ + Vit D group (group 5) received PQ + Vit D (5 mg/kg/d + 2 μg/kg/d, IP) and PQ + NAC group (group 6) received PQ + NAC (5 mg/kg/d + 6.25 mg/kg/d, IP). The animals were treated for 7 consecutive days as a sub-chronic exposure. After the collection of urea and serum creatinine, biomarkers of oxidative stress and kidney histopathology were investigated.

PQ increased lipid peroxidation (LPO), urea, and serum creatinine, but it significantly decreased total antioxidant capacity (TAC) and thiol groups. In the groups treated with Vit D and NAC, it was observed that LPO, urea, and creatinine significantly decrease compared with the PQ group, and TAC, thiol groups, and Vit D levels increased in kidney tissue.

The obtained findings revealed that both Vit D and NAC used as preventive compound were able to reduce oxidative stress and tissue damage caused by PQ toxicity in the kidney.

Peripheral pain regulation is a very complex phenomenon due to the numerous neural pathways responsible for it.

The current study aimed to determine the anti-nociceptive activity of L-citrulline and the possible role of opioidergic, nitric oxide (NO), and serotoninergic systems in mice using the formalin and hot plate tests.

In this study, 300 male NMRI mice were divided into 2 groups: 150 mice were used for the formalin test and 150 for the hot plate test (tests 1-6) with 4 sub-groups in each (n = 50). The formalin test determined pain caused by the injection of formalin in the hind paw, and the hot plate test recorded pain reactions caused by heat stimulation as response latency time. Further, time mice capable of staying on the rotarod bar were determined.

Morphine reduced licking and biting time and latency time in the hot plate (P < 0.05), while L-citrulline (50 and 100 mg/kg) decreased pain response and increased latency time compared to the control (P < 0.05). Further, pre-treatment with naloxone following L-citrulline increased licking and biting time in the formalin test and decreased latency time in the hot plate test (P < 0.05). In addition, pretreatment with L-NAME following L-citrulline diminished licking and biting time in the formalin test and increased latency time in the hot plate test (P < 0.05). Likewise, ad pre-treatment with ritanserin following L-citrulline reduced licking and biting time and latency time compared to control mice (P < 0.05). Similarly, licking and biting time and latency time were decreased by pre-treatment with ondansetron following L-citrulline. Finally, no significant disturbance was observed in motor coordination by L-citrulline (25, 50, and 100 mg/kg) at P > 0.05.

It seems that L-citrulline has anti-nociceptive effects, and its role is mediated by opioidergic, NO systems, as well as 5-HT2 and 5-HT3 receptors. Further, L-citrulline did not disturb motor coordination.

Fumaria officinalis is largely used in traditional medicine due to its efficiency in the treatment and prevention of numerous diseases and its large spectrum of therapeutic effects. Its multiple beneficial properties are due to its richness in bioactive substances, particularly isoquinoline alkaloids. However, few studies have addressed the toxicity of this plant.

The present work aimed to study acute and subacute toxicity of alkaloids extracted from F. officinalis using Swiss albino mice as the in vivo model.

Alkaloids from the aerial parts of F. officinalis were extracted and administered to male and female Swiss albino mice. The acute and subacute toxicities were studied by monitoring the weight and histopathological study of animal bodies and organs (e.g., liver, heart, spleen, and kidneys).

The results revealed that mice treated with increasing doses developed serious symptoms of toxicity (i.e., respiratory problems, tremors, coma, and paralysis leading the death) and lost weight. The LD50 was estimated at 1341.11 mg/kg permitting its classification as a low-toxic plant. The microscopic observations demonstrated disturbances in the kidney and liver, but not the heart and spleen.

The alkaloids of the aerial parts of F. officinalis expressed severe toxicity in mice, particularly at high doses. Nevertheless, the neutral fraction of alkaloids is more indicated.

Alcohol withdrawal syndrome (AWS) is a life-threatening condition affecting alcoholics who ceased or decreased their alcohol consumption. The synthetic drugs used to manage these consequences are not without undesirable effects; hence, the need for a natural and affordable approach is raised.

This study aimed at investigating the effect of aqueous extract of gum arabic (GA) on hepatorenal functions during ethanol withdrawal syndrome in Wistar rats.

In phase I, dose-response for GA and alcohol for the study were determined. In phase II, the effect of GA on biomarkers during AWS was studied. A total of 60 male Wistar rats were used for the study. Blood and tissue samples were obtained at the end of stipulated periods of oral administration for biochemical and histological analysis, and biochemical parameters were analyzed by spectrophotometry.

In the dose-response study, there were no significant differences (P ≥ 0.05) in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities as well as in total bilirubin (TBIL), malondialdehyde (MDA), sodium ion (Na + ), potassium ion (K + ), and creatinine concentrations in groups treated with 200 mg/kg body weight (bw) and 400 mg/kg bw GA aqueous extract compared to the control group. However, significant alterations were observed in groups treated with 600 and 800 mg/kg bw GA extract. Furthermore, rats that received 5.5 mL/kg bw alcohol showed marked changes in biochemical parameters compared to the group that received 4.5 mL/kg bw and the control group. The results obtained in Phase II exhibited the hepato-renal protective effect of GA during ethanol withdrawal. Statistical analysis of the obtained results indicated a better response from the study groups that were pre-treated or co-administered with GA compared to the group that was post-treated.

The result of this study suggests that GA aqueous extract offered better protection prophylactically than curatively.

Integrins are transmembrane mechanosensitive proteins that negatively contribute to the pathogenesis of different types of chronic liver disease and can activate focal adhesion kinase (FAK).

This study aimed to determine the hepatic integrin β1 and FAK mRNA as well as the transcriptional coactivator with PDZ-binding motif (TAZ) protein expressions in cirrhotic patients and simple steatosis.

In this case–control study, liver tissues were collected from 30 cirrhotic patients with various etiologies (i.e., nonalcoholic steatohepatitis-, primary sclerosing cholangitis-, alcoholic-, autoimmune hepatitis [AIH]- and hepatitis B virus [HBV]/hepatitis C virus [HCV]-related cirrhosis [six per group]), liver samples with simple steatosis (n = 6), and control liver tissues (n = 9).

Integrin β1 gene expression was significantly up-regulated in all cirrhotic groups compared to control group (P < 0.05), with the exception of AIH cirrhosis. However, hepatic FAK gene expression and TAZ protein level in the cirrhotic groups were not significantly different than those in the control group. Furthermore, hepatic integrin β1 and FAK gene expressions as well as TAZ protein level in simple steatosis were significantly lower than those in nonalcoholic steatohepatitis (NASH) cirrhosis and control (P < 0.05).

Integrin β1 was up-regulated in cirrhotic liver tissues. In addition, FAK, integrin β1, and TAZ were concordantly down-regulated in simple steatosis, and may have been involve in the steatosis development.

Prostate cancer is the second prevalent cancer and the fifth cause of deaths related to the men malignancies. The cancerous cell can travel from prostate to other parts of the body and cause metastasis in other organs such as bones and lymph nodes. For the treatment of the prostate cancer, chemotherapy and hormone therapy are being used. Hormone therapy in this disease is primarily based on the androgen suppression to prevent the growth and division of the cancerous cells. Different classes of drugs are used for hormone therapy. One group of these drugs is reducers of androgen production in adrenal glands. These drugs prevent the androgen production in adrenal glands and cancerous cells. Leuprorelin which is also known as leuprolide is a synthetic peptide that is used for treatment of prostate cancer.

The aim of this study is to explore novel anti-prostate cancer compounds using proteomics of microorganisms.

Leuprorelin synthetic peptide was chosen as the template for amino acid sequence homology search using blast, and the resulting protein of the best candidate sequences were employed as a query to perform docking test against the gonadotropin-releasing hormone receptor (GRHR) using HDOCK web server.

By employing an in silico approach, natural products with structure and function similar to leuprorelin were explored, and their features were characterized. A flippase-like domain-containing protein from Deltaproteobacteria bacterium showed strong binding to gonadotropin-releasing hormone receptor GRHR with docking score of -425. The absorption, distribution, metabolism, and excretion (ADME) tests showed no potential toxicity of this natural product to the body.

The present study demonstrated that the proteomics of living organisms contains natural compounds that can be considered a valuable source of medically important resources.

Coumarins comprise a large family of heterocyclic compounds with a benzo-a-pyrone moiety.

This study aimed to analyze the binding affinity of 3-(1H-tetrazol-5-yl) coumarin to bovine serum albumin (BSA) and calf thymus DNA (Ct-DNA) using fluorescence spectroscopy. The quenching of fluorescence was recognized during the interaction between 3-(1H-tetrazol-5-yl) coumarin and BSA, followed by a static mechanism.

The hydrogen bonds, hydrophobic interactions, and Vander Waals forces were regarded as the principal part in the 3-(1H-tetrazol-5-yl) coumarin and BSA complexation process. The fluorescence spectral characteristics demonstrated an enhancement in fluorescence intensity of the 3-(1H-tetrazol-5-yl) coumarin in the presence of ct-DNA solution.

The experimental results indicated that the 3-(1H-tetrazol-5-yl) coumarin binds to DNA via interjection, hydrogen bonds, and Vander Waals forces. This work illustrated that BSA fluorescence was quenched by 3-(1H-tetrazol-5-yl) coumarin via a static mechanism and the ct-DNA fluorescence enhancement by 3-(1H-tetrazol-5-yl) coumarin was a static process. The secondary structure of proteins changed upon drug binding.

It is deduced that 3-(1H-tetrazol-5-yl) coumarin represents a higher binding affinity to DNA compared to BSA. This finding can be useful in designing more effective new drugs with fewer side effects.