Search results for: Liver X receptor (LXR)

Authors: M. Krishna

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The study was intended to identify if scalp cooling therapy is effective on preventing chemotherapy-induced hair loss among cancer patients. Critical literature of non-randomized controlled trials was used to investigate whether scalp cooling therapy is effective on preventing chemotherapy-induced alopecia. The review identified that scalp cooling therapy is effective on preventing chemotherapy-induced alopecia. Most of the patients receiving chemotherapy experience alopecia. It is also perceived as the worst effect of chemotherapy. This may be severe and lead the patients to withdraw the chemo treatment. The image disturbance caused by alopecia will make the patient depressed and will lead to declined immunity. With the knowledge on effectiveness of scalp cooling therapy on preventing chemotherapy-induced alopecia, patient undergoing chemotherapy will not be hesitant to undergo the treatment. Patients are recommended to go through scalp cooling therapy every chemo cycle and the proper therapy duration is 30 minutes before, during chemo. The suggested duration of the scalp cooling therapy is 45-90 minutes for an effective and positive outcome. This finding is excluding other factors of alopecia such as menopause, therapeutic drugs, poor hair density, liver function problems, and drug regimes.

Keywords: alopecia, cancer, chemotherapy, scalp cooling therapy

Procedia PDF Downloads 184

Authors: Shikha Rani, Neeta Sehgal, Vipin Kumar Verma, Om Prakash

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Introduction: Fish is an important protein source for humans and has great economic value. Fish cultures are affected due to various anthropogenic activities that lead to bacterial and viral infections. Aeromonas hydrophila is a fish pathogenic bacterium that causes several aquaculture outbreaks throughout the world and leads to huge mortalities. In this study, plants of no commercial value were used to investigate their immunostimulatory, antioxidant, anti-inflammatory, anti-bacterial, and disease resistance potential in fish against Aeromonas hydrophila, through fish feed fortification. Methods: The plant was dried at room temperature in the shade, dissolved in methanol, and analysed for biological compounds through GC-MS/MS. DPPH, FRAP, Phenolic, and flavonoids were estimated following standardized protocols. In silico molecular docking was also performed to validate its broad-spectrum activities based on binding affinity with specific proteins. Fish were divided into four groups (n=6; total 30 in a group): Group 1, non-challenged fish (fed on a non-supplemented diet); Group 2, fish challenged with bacteria (fed on a non-supplemented diet); Group 3 and 4, fish challenged with bacteria (A. hydrophila) and fed on plant supplemented feed at 2.5% and 5%. Blood was collected from the fish on 0, 7th, 14th, 21st, and 28th days. Serum was separated for glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase assay (ALP), lysozyme activity assay, superoxide dismutase assay (SOD), lipid peroxidation assay (LPO) and molecular parameters (including cytokine levels) were estimated through ELISA. The phagocytic activity of macrophages from the spleen and head kidney, along with quantitative analysis of immune-related genes, were analysed in different tissue samples. The digestive enzymes (Pepsin, Trypsin, and Chymotrypsin) were also measured to evaluate the effect of plant-supplemented feed on freshwater fish. Results and Discussion: GC-MS/MS analysis of a methanolic extract of plant validated the presence of key compounds having antioxidant, anti-inflammatory, anti-bacterial, anti-inflammatory, and immunomodulatory activities along with disease resistance properties. From biochemical investigations like ABTS, DPPH, and FRAP, the amount of total flavonoids, phenols, and promising binding affinities towards different proteins in molecular docking analysis helped us to realize the potential of this plant that can be used for investigation in the supplemented feed of fish. Measurement liver function tests, ALPs, oxidation-antioxidant enzyme concentrations, and immunoglobulin concentrations in the experimental groups (3 and 4) showed significant improvement as compared to the positive control group. The histopathological evaluation of the liver, spleen, and head kidney supports the biochemical findings. The isolated macrophages from the group fed on supplemented feed showed a higher percentage of phagocytosis and a phagocytic index, indicating an enhanced cell-mediated immune response. Significant improvements in digestive enzymes were also observed in fish fed on supplemented feed, even after weekly challenges with bacteria. Hence, the plant-fortified feed can be recommended as a regular feed to enhance fish immunity and disease resistance against the Aeromonas hydrophila infection after confirmation from the field trial.

Keywords: immunostimulation, antipathogen, plant fortified feed, macrophages, GC-MS/MS, in silico molecular docking

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Authors: M. M. Alsharif

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4-Nonylphenol Compound is widely used as an element of detergents, paints, insecticides and many others products. It is known that the existence of this compound may lead to the emission of estrogenic responses in mammals, birds and fish. It is described as pollutant since it causes disorder of endocrine glands. In previous studies, it was proven that this compound exists in water and in the materials precipitated in Red Sea coast in Jeddah near the drains of processed drainage water and near the drainage site of the residuals of paper factories. Therefore, this study aimed to evaluate the cytogenetic aberrations caused by 4-nonylphenol through exposing Talapia Fishes to aquatic solution of the compound with 0, 15, 30 microgram/liter for one month. Samples of gills and liver were collected for micronuclei, nuclear abnormalities and measuring DNA and RNA amount in the treated fish. The results pointed out that there is a significant increase in the numbers of micronuclei in the fish exposed to the former concentrations as compared to the control group. Exposing fishes to 4-nonylphenol resulted in an increased amount of both DNA and RNA, compared to the control group. There is a positive correlation between the amount of the compound (i.e. dosage dependent effect) and the inspiring for cytogenetic effect on Talapia fishes in Jeddah. Therefore, micronucleus test, DNA and RNA contents can be considered as an index of cumulative exposure, which appear to be a sensitive model to evaluate genotoxic effects of 4-Nonylphenol compound on fish.

Keywords: genotoxic, 4-nonylphenol, micronuclei, fish, DNA, RNA

Procedia PDF Downloads 283

Authors: Salaam Mujeeb, Adeola Segun, Abdullahi Olasunkanmi

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Dementia is becoming a major concern as the world population is increasing and elderly populations are being neglected. Liver and kidney Diseases have been implicated as risk factors in the etiology of Dementia. This study, therefore, evaluates the plasma Gamma Glutamyl Transferase (GGT) activity and plasma Electrolytes in other to find an association between the biomarkers and Dementia. The subjects (38) were age and sex-matched with their corresponding controls and structured questionnaires were used to obtain medical information. Using spectrophotometric and ion selective Electrode techniques respectively, we found and elevated GGT activity in the Dementia Subjects. Remarkably, no association was found between the plasma Electrolytes level and Dementia subjects. It was also observed that severity of Dementia worsens with age. Moreover, the condition of the dementia subjects worsens with reducing weight. Furthermore, the presence of Comorbidity e.g. Hypertension, Obesity, Diabetes and Habits like Smoking, Drugs and Alcohol consumption interferes with Electrolyte balance. Weight loss monitoring and IBM check are advised in Elderly individuals particularly females as they may be inductive of early or future cognitive impairments. Therefore, it might be useful as an early detection tool. Government and society should invest more on the Geriatric population by establishing Old people's home and providing social care services.

Keywords: clinical characteristics, dementia, electrolytes, gamma glutamyl transpeptidase, GGT

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Authors: Sheimah El Bejjaji, Lara Gorsek, Chandler Quilchez, Joaquim Suñer, Mireia Mallandrich

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Flurbiprofen is an anti-inflammatory drug used in several treatments. The purpose of this study was to compare the permeation of two different formulations of flurbiprofen through the human skin. The first formulation was a solution of flurbiprofen dissolved with polyethylene glycol 3350 (PEG 3350). The second formulation was flurbiprofen encapsulated in poly-ɛ-caprolactone (PɛCL) nanoparticles (NPs), stabilized with poloxamer 188, submitted individually for freeze-drying with PEG 3350 as a cryoprotectant and sterilized by gamma-irradiation. Human skin was obtained from the abdominal region of a healthy patient. The experimental protocol was approved by the Bioethics Committee of Barcelona SCIAS Hospital (Spain), and they obtained the written informed consent forms. After being frozen to -20ºC, the skin samples were cut with a dermatome at 400 µm. The ex vivo permeation study was performed in Franz diffusion cells with a diffusion area of 2.54 cm². Skin samples were placed between two compartment sites, the dermal side in contact with the receptor medium and the epidermis side in contact with the donor chamber to which the formulation was applied. The permeation study was conducted for 24 hours at 32 ± 0.5 °C in accordance with sink conditions. The results were analyzed with an unpaired t-test, and the p-values indicate the formulation with nanoparticles had a higher permeability coefficient, flux, partition parameter, diffusion parameter, and lag time. The applicability of this formulation topically can benefit articulations and ligament inflammation as an alternative to oral drugs.

Keywords: anti-inflammatory drug, flurbiprofen, human skin, nanoparticles, skin permeation

Procedia PDF Downloads 71

Authors: Merrick Lopez, Aashish Abraham, Melissa Egge, Marissa Hood, Jui Shah

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A 3 year old male with unknown medical history presented initially with encephalopathy, intubated for respiratory failure, and admitted to the pediatric intensive care unit (PICU) with refractory shock. During resuscitation in the emergency department, he was found to be in severe metabolic acidosis with a pH of 7.03 and escalated on vasopressor drips for hypotension. His initial sodium was 174. He was noted to have burn injuries to his scalp, forehead, right axilla, bilateral arm creases and lower legs. He had rhabdomyolysis (initial creatinine kinase 5,430 U/L with peak levels of 62,340 normal <335 U/L), cardiac injury (initial troponin 88 ng/L with peak at 145 ng/L, normal <15ng/L), hypernatremia (peak 174, normal 140), hypocalcemia, liver injury, acute kidney injury, and neuronal loss on magnetic resonance imaging (MRI). Soft restraints and a shock collar were found in the home. He was critically ill for 8 days, but was gradually weaned off drips, extubated, and started on feeds. Discussion Electrical injury, specifically lightning injury is an uncommon but devastating cause of injury in pediatric patients. This patient with suspected abusive use of a dog shock collar presented similar to a lightning strike. Common entrance points include the hands and head, similar to our patient with linear wounds on his forehead. When current enters, it passes through tissues with the least resistance. Nerves, blood vessels, and muscles, have high fluid and electrolyte content and are commonly affected. Exit points are extremities: our child who had circumferential burns around his arm creases and ankles. Linear burns preferentially follow areas of high sweat concentration, and are thought to be due to vaporization of water on the skin’s surface. The most common cause of death from a lightning strike is due to cardiopulmonary arrest. The massive depolarization of the myocardium can result in arrhythmias and myocardial necrosis. The patient presented in cardiogenic shock with evident cardiac damage. Electricity going through vessels can lead to vaporization of intravascular water. This can explain his severe hypernatremia. He also sustained other internal organ injuries (adrenal glands, pancreas, liver, and kidney). Electrical discharge also leads to direct skeletal muscle injury in addition to prolonged muscular spasm. Rhabdomyolysis, the acute damage of muscle, leads to release of potentially toxic components into the circulation which could lead to acute renal failure. The patient had severe rhabdomyolysis and renal injury. Early hypocalcemia has been consistently demonstrated in patients with rhabdomyolysis. This was present in the patient and led to increased vasopressor needs. Central nervous system injuries are also common which can include encephalopathy, hypoxic injury, and cerebral infarction. The patient had evidence of brain injury as seen on MRI. Conclusion Electrical injuries due to lightning strikes and abusive use of a dog shock collar are rare, but can both present in similar ways with respiratory failure, shock, hypernatremia, rhabdomyolysis, brain injury, and multiorgan damage. Although rare, it is essential for early identification and prompt management for acute and chronic complications in these children.

Keywords: cardiogenic shock, dog shock collar, lightning strike, rhabdomyolysis

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Authors: Sagarjyoti Roy

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Dengue is an arboviral infection, belonging to family flaviviridae, comprising of four serotypes; DENV1, DENV2, DENV3 and DENV4. All four serotypes are capable of causing full-spectrum of clinical features, ranging from self-limiting fever to severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Complications may affect any organ system, including those involving gastrointestinal system and serositis. We report a case, of a 28 years, non-alcoholic male, presenting with a 7 day history of fever and malaise followed by abdominal pain and distension, from 4th day of fever. He was admitted in medicine department of RG KAR medical college hospital. Dengue fever was confirmed by NS1 and dengue IgM positivity. Platelet count was 30,000/cc (1.5- 4 lac/cc) and haematocrit was 52% (38- 50% for men). Clinicoradiological findings revealed bilateral pleural effusion, ascites and splenomegaly. Ascitic fluid was hemorrhagic in nature, with a high protein and RBC content. Liver function tests revealed mild transaminitis with normal coagulation profile. Patient was managed conservatively. A diagnosis of dengue fever complicated by serositis and spontaneous haemoperitoneum was made. The symptoms subsided after a hospital stay of 10 days. The case highlights haemorrhage into peritoneal cavity as a possible complication of dengue fever. Although a definite explanation requires more detailed studies, platelet or endothelial cell dysfunction might be contributory.

Keywords: ascites, dengue, haemoperitoneum, serositis

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Authors: Zerrin Orbak, Busra Demir

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Osteopetrosis is a rare genetic disease characterized by impaired bone resorption and increased bone sclerosis. Clinical presentation is very different in osteopetrosis. It can be asymptomatic or can be seen with typical symptoms. Here, a case of osteopetrosis was presented when evaluated for nystagmus. She was 10 months old. Parents were second-degree relatives. On physical examination, pigeon chest deformity and horizontal nystagmus were observed. There was a failure of thrive but no fracture. The cardiovascular examination was normal. Cranial, vertebral and long bone roentgenograms revealed characteristic deformities of osteopetrosis and diffuse sclerosis. The diagnosis was confirmed by genetic testing. A Homozygous mutation was detected in the TNFRSF11A gene (c.508A>G p.(Arg170Gly)). RANKL is encoded by the tumor necrosis factor ligand superfamily member 11 (TNFSF11) gene, and the binding to its receptor RANK, encoded by the TNFRSF11A gene, determines the activation of the downstream pathway that drives osteoclast differentiation and activation (51). The complete absence of osteoclasts is the key feature of the osteoclast-poor form of osteopetrosis (46). Patients are characterized by the absence of TRAP-positive osteoclasts in bone biopsies. The osteoclast-poor subtype of osteopetrosis caused by mutations in TNFSF11 gene is ultra-rare in humans. Clinical presentation is usually severe, with onset in early infancy or in fetal life. But here, a case was presented with horizontal nystagmus. A case presented with horizontal nystagmus, which was evaluated by neurology and diagnosed incidentally, was shared.

Keywords: osteopetrosis, nystagmus, bone, osteoclast-poor

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Authors: B.S. Roopa

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Objectives: To investigate the prevalence of concomitant use of GPDs in patients treated with NSAIDs and GPDs in recommended dose and frequency as prophylaxis. And also to know the association between risk factors and prescription of GPDs in patients treated with NSAIDs. Methods: Study was a prospective, observational, cross-sectional survey. Data from patients with prescription of NSAIDs at the out-patient departments of secondary care Hospital, Nilgiris, India were collected in a specially designed proforma for a period of 45 days. Analysis using χ2 tests for discrete variables. Factors that might be associated with prescription of GPD with NSIADs were assessed in multiple logistic regression models. Results: Three hundred and three patients were included in this study, and the rate of GPD prescription was 89.1%. Most of the patients received H2-receptor antagonist, and, to a lesser degree, antacid and proton pump inhibitor. Patients with history of GI ulcer/bleeding were much more likely to be co-prescribed GPD than those who had no history of GI disorders .Compared with patients who were managed in general outpatient clinic, those managed in Secondary care hospital in Nilgrisis, India were more likely to receive GPD. Conclusions: The prescription rate of GPD with NSAIDs is high. Patients were prescribed with H2RA with dose of 150mg twice daily, which are not effective in reducing the risk of NSAIDs induced gastric ulcer. Only the frequency of NSAIDs prescription was considered significant determinant for the co-prescription with GPAs in patients who are < 65 years and ≥ 65 years old.

Keywords: gastro protective agents, non steridol anti inlfammatory agents

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Authors: N. Chikhi-Chorfi, L. Arbia, S. Zenia, H.Lounici

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Opuntia ficus-indica belongs to the Cactaceae family. The cactus is mainly cultivated for its fruit (prickly pear) that, eaten after pealing, is sweet and juicy, and rich in nutritional compounds, such as ascorbic acid and polyphenols. Different parts of O. ficus-indica are used in the traditional medicine of several countries: the cladodes are utilized to reduce serum cholesterol level and blood pressure, for treatment of ulcers, rheumatic pain, wounds, fatigue, capillary fragility, and liver conditions. This original study, investigate the effect of polyphenols of O. ficus indica (cactus) cladodes against periodontal bacteria collected from patients with periodontitis. The quantitative analysis of total polyphenols (TPP) was determined with Follin-Ciocalteu method. Different concentrations of extracts of O. ficus indica were tested by the disk method on two bacterial strains: Porphyromonas gingivalis and Prevotella intermedia responsible for periodontal disease. The results showed a good correlation between the concentration of total polyphenols and the antibacterial activity of the extracts of Opuntia ficus indica against P. gingivalis and P. intermedia with R² = 0.94 and R² = 0.90 respectively. This observation suggests that these extracts could be used in the treatment and prevention of periodontitis.

Keywords: periodontal disease, P. gingivalis, P. intermedia, polyphenols, Opuntia ficus indica

Procedia PDF Downloads 124

Authors: Deepika Saini, Sandeep Jain, Ajay Kumar

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The quinoline scaffold is one of the most widely studied in the discovery of derivatives with various heterocyclic moieties due to its potential antimalarial activities. In the present study, a chalcone series of quinoline derivatives clubbed with pyrazole were synthesized to evaluate their antimalarial property by in vitro schizont maturation inhibition assay against both chloroquine sensitive, 3D7 and chloroquine resistant, RKL9 strain of Plasmodium falciparum. Further, top five compounds were studied for in vivo preclinical study for antimalarial potential against P. berghei in Swiss albino mice. To understand the mechanism of synthesized analogues, they were screened computationally by molecular docking techniques. Compounds were docked into the active site of a protein receptor, Plasmodium falciparum Cysteine Protease Falcipain-2. The compounds were successfully synthesized, and structural confirmation was performed by FTIR, 1H-NMR, mass spectrometry and elemental analysis. In vitro study suggested that the compounds 5b, 5g, 5l, 5s and 5u possessed best antimalarial activity and further tested for in vivo screening. Compound 5u (CH₃ on both rings) with EC₅₀ 0.313 & 0.801 µg/ml against CQ-S & CQ-R strains of P. falciparum respectively and 78.01% suppression of parasitemia. The molecular docking studies of the compounds helped in understanding the mechanism of action against falcipain-2. The present study reveals the binding signatures of the synthesized ligands within the active site of the protein, and it explains the results from in vitro study in their EC₅₀ values and percentage parasitemia.

Keywords: antimalarial activity, chalcone, docking, quinoline

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Authors: Ryan Stevens, Wayne L. Bryden

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This study focused on the effects of ginger and a zeolite (toxin binder) in reducing the toxic effects of aflatoxin B1 (AFB1) in broiler chickens 7 to 49 days of age. The chicks were maintained normally until experimental diets were introduced on day 7 post-hatching. Nine hundred and thirty six, 7-d-old broiler chickens were randomly assigned to 18 treatment groups; each group had four replicates, each with 13 chickens. The experimental groups or diets had factorial combinations of the following; AFB1 0, 1 and 2 mg/kg diet, ginger 0 and 5g/kg diet, and zeolite 0, 15 and 30 g/kg diet. Diets were based on corn and soybean meal and a starter diet was fed from 1 to 14 days, a grower diet from15 to 28 days and a finisher diet was provided from day 29 until the end of the experiment. Both dietary levels of AFB1 decreased (P<0.05) body weight and feed conversion, and increased relative liver weights. Independent dietary inclusion of ginger or zeolite restored chick performance when diets contained 1mg/kg but not at 2mg/kg. Supplementation of zeolite together with ginger improved performance of birds fed contaminated diets. Interestingly, adding ginger to the control diet that was not contaminated with AFB1 improved (P<0.05) performance. Our results suggest that toxin binders and ginger can provide protection against the negative effects of AFB1 on performance of broiler chicks.

Keywords: aflatoxin, broiler, ginger, zeolite

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Authors: Eunhwa Jun

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This case report describes the misdiagnosis of a patient who presented with right arm pain as cervical disc herniation. The patient had several underlying conditions, including hypertension, diabetes mellitus, liver cirrhosis, a history of lung cancer with left lower lobe lobectomy, and adjuvant chemoradiotherapy. An external cervical spine MRI revealed central protruding discs at the C4-5-6-7 levels. Despite treatment with medication and epidural blocks, the patient's pain persisted. A C-RACZ procedure was planned, but the patient's pain had worsened before admission. Using ultrasound, a brachial plexus block was attempted, but the brachial plexus eluded clear visualization, hinting at underlying neurological complexities. Chest CT revealed a new, large soft tissue mass in the right supraclavicular region with adjacent right axillary lymphadenopathy, leading to the diagnosis of metastatic squamous cell carcinoma. Palliative radiation therapy and chemotherapy were initiated as part of the treatment plan, and the patient's pain score decreased to 3 out of 10 on the Numeric Rating Scale (NRS), revealing the pain was due to metastatic lung cancer.

Keywords: supraclavicula brachial plexus metastasis, cervical disc herniation, brachial plexus block, metastatic lung cancer

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Authors: Elsayed Fath Khalifa, Samer Mohamed Daghash

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The aim of the current work study to increase the anatomical knowledge about the cattle egret which considered economically important for farmers. The study was carried out on ten adult, apparently healthy cattle egrets of both sexes. Each bird was exsanguinated; the caudal vena cava was cannulated and flushed with warm normal saline solution (0.9%) then injected with blue colored neoprine (60%) latex in order to study the tributaries of the hepatic portal vein. The origin, course and tributaries of the right and left hepatic portal veins were studied. The hepatic portal venous system collected venous blood from the abdominal viscera including; glandular and muscular stomachs, liver, pancreas, spleen, small intestine and large intestine. The hepatic portal vein was formed by the left and the right hepatic portal veins. The smaller left one drained blood from the glandular and muscular stomachs through the ventral and the left proventriculus as well as the left gastric veins. The most tributaries of the right hepatic portal vein drained blood from the rest of the gastrointestinal tract and the spleen by the proventriculosplenic, the gastropancreaticoduodenal and the common mesenteric veins.

Keywords: cattle egret, common mesenteric vein, hepatic portal vein, anatomy

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Authors: Hu-Jiang Shi, Li-Juan Zhu

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The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) in affective behaviors is a topic of debate, and the underlying mechanisms remain largely unclear. Here, we elucidate that the interaction between hippocampal neuronal nitric oxide synthase (nNOS) and carboxy-terminal PDZ ligand of nNOS (CAPON) contributes to the disruption of hippocampal excitation-inhibition (E/I) balance, which is responsible for the anxiety- and depressive-like behaviors caused by chronic stress-related 5-HT2CR signaling deficiency. In detail, activation or inhibition of 5-HT2CR by CP809101 or SB242084 modulates nNOS-CAPON interaction by influencing intracellular Ca²⁺ release. Notably, the dissociation of nNOS-CAPON abolishes SB242084-induced anxiety- and depressive-like behaviors, as well as the reduction in extracellular signal-regulated kinase (ERK)/cAMP-response element binding protein (CREB)/synapsin signaling and SNARE complex assembly. Furthermore, nNOS-CAPON blockers restore the impairments caused by SB242084, including the reduction in SNARE assembly-mediated γ-aminobutyric acid (GABA) vesicle release and a consequent shift of the E/I balance toward excitation in CA3 pyramidal neurons. Conclusively, our findings disclose the regulatory role of 5-HT2CR in anxiety- and depressive-like behaviors and highlight the hippocampal nNOS-CAPON coupling-triggered E/I imbalance as a pivotal cellular event underpinning the behavioral consequences of 5-HT2CR inhibition.

Keywords: 5-HT2CR, anxiety, depression, nNOS-CAPON coupling, excitation-inhibition balance, neurotransmitter release

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Authors: Afaf Benhouda, Mouloud Yahia, Hachani Khadraoui, Asma Meddour, Souhila Benbia, Abdelmoudjib Ghecham, Djahida Benhouda

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Umbilicus rupestris (UR) is an herbal medicine traditionally applied against the ignitions of the skin. The present paper aimed to study the acute and subacute toxicity with orally administered methanolic leaves extract of Umbilicus rupestris L (URMeOH). In acute toxicity tests, four groups of rats (n = 6/group/female) were orally treated with doses of 500, 1000, 1500 and 2000 mg/kg, and general behaviour, adverse effects, and mortality were recorded for up to 14 days. In subacute toxicity study, rats received URAMeOH by gavage at the doses of 100, 200 mg/kg/day (n = 6/group) for 28 days, and biochemical, hematological, and histopathological changes in tissues (liver, kidney) were determined. URMeOH did not produce any hazardous symptoms or death and in the acute toxicity test. Subacute treatment with URMeOH did not show any change in body weight, and hematological and biochemical profiles. In addition, no change was observed either in macroscopic or microscopic aspects of vital organs in rats. Our result showed that Umbilicus rupestris extract could be safe for human use.

Keywords: acute toxicity, biochemical parameters, hematological parameters, Umbilicus rupestris, subacute toxicity

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Authors: A. M. Gadanya, M. S. Sule

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Effect of oral administration of Gadagi tea on some antioxidant enzymes was assessed in healthy male albino rats. The rats were grouped and administered with standard doses of the 3 types of Gadagi tea i.e. Sak, Sada and Magani for a period of four weeks. Animals that were not administered with the tea constituted the control group. At the end of fourth week, the animals were sacrificed and their serum superoxide dismutase (SOD), glutathione reductase (GR) and catalase (CAT) activities were determined. The activities of the enzymes were also determined in the brain, liver, kidney and intestine homogenates of the rats. Mean SOD activity in brain of rats orally administered with “sada” was found to be significantly higher (P < 0.05) than that of the control group. Mean CAT activity in the intestine of rats orally administered with “magani” was found to be significantly higher (P < 0.05) than that of the control group and the experimental groups of Sak and Sada at standard dose level. Thus, all the “Gadagi” tea preparations studied at standard dose level could stimulate antioxidant enzymes, especially SOD in brain and CAT in intestine (by Sada) and CAT in intestine (by Magani).

Keywords: “Gadagi” tea, superoxide dismutase, catalase, glutathione reductase

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Authors: T. Hojageldiyev, Y. Bolmammedov, S. Gurbanaliyev

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It is known that drugs used in the treatment of tuberculosis show toxic effect to organism especially to liver besides its therapeutic effect. Because of ineffectiveness of drugs used in the treatment regimen of tuberculosis against multidrug resistance (MDR) and extensively drug-resistance (XDR) tuberculosis requires the development of new treatment methods and new, novel drugs. Considering the usage of Artemisia absinthium in traditional medicine in treatment of wounds which suggests its antibacterial activity it seems that, also it may have significant antimycobacterial activity. The objective of present study was to evaluate antibacterial activity of ethanolic extract of A. absinthium against M. tuberculosis. In this study, the effect of ethanolic extract of A. absinthium was tested against tuberculosis and pharmaco-toxicological properties evaluated on laboratory animals. The 20%, 40%, 70% and 96% ethanolic extracts of A. absinthium prepared then its bacteriostatic and bactericidal activities were evaluated by validated methods. Data were analyzed by GraphPad Prism 7.0 at the level P < 0.05. Results showed that ethanolic extracts of A. absinthium show no toxicological properties with having high LD50. All concentrations of extract show high bacteriostatic activity on M. tuberculosis. 96% ethanolic extract has highest bactericidal effect among other concentrations. By conducting further studies, as a result of our study, antimycobacterial drug can be prepared from A. absinthium.

Keywords: Artemisia absinthium, antimycobacterial, ethanolic extract, Mycobacteria tuberculosis

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Authors: Urarat Nanna, Jarinyaporn Naowaboot

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Tiliacora triandra (T. triandra) is traditional Southeast Asian medicine and widely used in the cuisines of northeast Thailand and Laos. It has been used as antipyretic, detoxication agent, antiinflammation. But the activity of T. triandra leaf water extract (TTW) in the regulation of metabolic syndrome is still little known. In this study, we evaluated the effects of TTW in high-fat diet (HFD)-induced obese mice. Male ICR mice were induced to be obese by HFD feeding (45 kcal% lard fat) for 12 weeks. During the last 6 weeks of diet feeding, the obese mice were treated with TTW at 250 and 500 mg/kg/day. The biochemical parameters and histology analysis were measured at the end of treatment period. After 6 weeks of TTW treatment, the hyperglycemia, hyperinsulinemia, hyperleptinemia and hyperlipidemia were significantly decreased. Hepatic lipid accumulation and adipocyte hypertrophy were also reduced. Serum adiponectin was increased in TTW-treated obese mice. TTW treatment could reduce the malondialdehyde in serum and liver tissue. Furthermore, the elevated serum inflammatory cytokines, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 were reduced (MCP-1) by TTW. These results suggest that T. triandra leaf is a beneficial plant in alleviating hyperglycemia, hyperlipidemia, oxidative stress and inflammation in the obese condition induced by HFD.

Keywords: Tiliacora triandra, insulin resistance, hyperlipidemia, oxidative stress

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Authors: Ahmad Daryani, Yousef Dadimoghaddam, Mehdi Sharif, Ehsan Ahmadpour, Shahabeddin Sarvi, Baghar Hashemi

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Background: Excretory-secretory antigens (ESAs) of Toxoplasma gondii are one of the candidates for immunization against toxoplasmosis. For evaluation of immunization, we determined the kinetics of the distribution of Toxoplasma and parasite load in different tissues of mice immunized by ESAs. Methods: In this experimental study, 36 mice in case (n= 18) and control (n= 18) groups were immunized with ESAs and PBS, respectively. After 2 weeks, mice were challenged intraperitoneally with Toxoplasma virulent RH strain. Blood and different tissues (brain, spleen, liver, heart, kidney, and muscle) were collected daily after challenge (1, 2, 3 and last day before death). Parasite load was calculated using Real time QPCR targeted at the B1 gene. Results: ESAs as vaccine in different tissues showed various effects. However, infected mice which received the vaccine in comparison with control group, displayed a drastically decreasing in parasite burden, in their blood and tissues (P= 0.000). Conclusion: These results indicated that ESAs with reduction of parasite load in different tissues of host could be evaluable candidate for the development of immunization strategies against toxoplasmosis.

Keywords: parasitic load, murine toxoplasmosis, immunization, excretory-secretory antigens, real time QPCR

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Authors: Hakim Chayeb

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Macrophages (Mo) play an essential role in host defense against pathogens. These inflammatory cells contain a large group of inducible enzymes such as NO synthase (NOS). This study was conducted to characterize experimentally induced inflammation in vivo by lipopolysaccharides (LPS). LPS is an essential component of the outer membrane of Gram-negative bacteria and a potent inducer of macrophage. Except control rats, all rats received different doses of LPS intra-peritoneally. The involvement of inducible NO synthase (iNOS) and constitutive (cNOS ) in the modulation of the inflammatory response was studied by treating the rats with L-NAME (non-selective NOS inhibitor) or aminoguanidine (AG inhibitor of iNOS). Inhibitors were injected 24 hours before LPS administration. The results showed that esterase activity (a marker of macrophage infiltration) which is induced by LPS is reduced by AG, was potentiated by treatment with L-NAME in tissue homogenates of the liver, kidney and spleen. Meanwhile, the concentrations of nitric oxide (NO) induced by LPS were reduced with AG and are completely inhibited with L-NAME in the tissues studied. NO concentrations and plasma transaminase levels have undergone remarkable increases in rats treated with LPS alone. However, the AG significantly reduced these rates. Our results highlighted the role of NO synthase inhibitors in reducing of inflammatory responses that characterize many infectious diseases.

Keywords: aminoguanidine, esterase, LPS, L-NAME, macrophage, nitric oxide

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Authors: Stela Papa, Klementina Puto, Migena Pllaha

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HCV is a hepatotropic RNA virus, transmitted primarily via the blood route, which causes progressive disease such as chronic hepatitis, liver cirrhosis, or hepatocellular carcinoma. HCV nowadays is a global healthcare problem. A variety of immunoassays including old and new technologies are being applied to detect HCV in our country. These methods include Immunochromatography assays (ICA), Fluorescence immunoassay (FIA), Enzyme linked fluorescent assay (ELFA), and Enzyme linked immunosorbent assay (ELISA) to detect HCV antibodies in blood serum, which lately is being slowly replaced by more sensitive methods such as rapid automated analyzer chemiluminescence immunoassay (CLIA). The aim of this study is to estimate HCV infection in carriers and chronic acute patients and to evaluate the use of new diagnostic methods. This study was realized from September 2016 to May 2018. During this study period, 2913 patients were analyzed for the presence of HCV by taking samples from their blood serum. The immunoassays performed were ICA, FIA, ELFA, ELISA, and CLIA assays. Concluding, 82% of patients taken in this study, resulted infected with HCV. Diagnostic methods in clinical laboratories are crucial in the early stages of infection, in the management of chronic hepatitis and in the treatment of patients during their disease.

Keywords: CLIA, ELISA, Hepatitis C virus, immunoassay

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Authors: Maged Syed Ahamd, Manal Mohamed Yasser, Essam Sholkamy

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In this paper, we reported that selenium (Se) nanoparticles were firstly biosynthesized with a simple and eco-friendly biological method. Their shape, size, FTIR (Fourier Transform Infrared spectroscopy), UV–vis spectra, TEM (Transmission Electron Microscopy) images and EDS (Energy Dispersive Spectroscopy) pattern have been analyzed. TEM analyses of the samples obtained at different stages indicated that the formation of these Se nanostructures was governed by an incubation time (12- 24- 48 hours). The Se nanoparticles were initially generated and then would transform into crystal seeds for the subsequent growth of nanowires; however obtaining stable Se nanowire with a diameter of about 15-100 nm. EDS shows that Se nanoparticles are entirely pure. The IR spectra showed the peaks at 550 cm-1, 1635 cm-1, 1994 cm-1 and 3430 cm-1 correspond to the presence of Se-O bending and stretching vibrations. The concentrations of Se-NPs (0, 1, 2, 5 µg/ml) did not give significantly effect on both two cell lines while the highest concentrations (10- 100 µg/ml gave significantly effects on them. The lethal dose (ID50%) of Se-NPs on Hep2 G and MCF-7 cells was obtained at 75.96 and 61.86 µg/ml, respectively. Results showed that Se nanoparticles as anticancer agent against MCF-7 cells were more effective than Hep2 G cells. Our results suggest that Se-NPs may be a candidate for further evaluation as a chemotherapeutic agent for breast and liver cancers.

Keywords: selenium nanoparticle, Streptomyces bikiniensis, nanowires, chemotherapeutic agent

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Authors: Jiandong Ren, Lijun Zhao, Peng Chen

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Nafamostat (NA), a synthetic broad-spectrum serine protease inhibitor, has been routinely employed for the treatment of acute pancreatitis (AP) and other inflammatory-associated diseases in some East Asia countries. Although the potent inhibitory activity against inflammation-related proteases such as thrombin, trypsin, kallikrein, plasmin, coagulation factors and complement factors is generally considered to be responsible for the anti-inflammatory effects of NA, precise target and molecular mechanism underlying the anti-inflammatory activity in the treatment of AP remain largely unknown yet. As an intracellular inflammatory signaling platform, the NOD-like receptor protein 3 (NLRP3) inflammasome is recently identified to be involved in the development of AP. In present study, we have revealed that NA alleviated pancreatic injury in a caerulein-induced AP model by inhibiting the NLRP3 inflammasome activation in pancreas. Mechanistically, NA interacted with HDAC6, a cytoplasmic deacetylase implicated in the NLRP3 inflammasome pathway, and efficiently abrogated the function of HDAC6. This property enabled NA to influence HDAC6 dependent NF-κB transcriptional activity and thus block NF-κB-driven transcriptional priming of NLRP3 inflammasome. Moreover, NA exerted the potential to interfere HDAC6-mediated intracellular transport of NLRP3, thereby leading to the failure of NLRP3 inflammasome activation. Our current work has provided valuable insight into the molecular mechanism underlying the immunomodulatory effect of NA in treatment of AP, highlighting its promising application in prevention of NLRP3 inflammasome-associated inflammatory pathological damage.

Keywords: acute pancreatitis, HDAC6, nafamostat, NLRP3 inflammasome

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Authors: Sarah Nasr, Maha M. A. Nasra, Ossama Y. Abdallah

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The present work aimed to prepare Silymarin loaded MCM-41 type mesoporous silica nanoparticles (MSNs) and to assess the system’s solubility enhancement ability on the pharmacodynamic performance of Silymarin as a hepatoprotective agent. MSNs prepared by soft-templating technique, were loaded with Silymarin, characterized for particle size, zeta potential, surface properties, DSC and XRPD. DSC and specific surface area data confirmed deposition of Silymarin in an amorphous state in MSNs’ pores. In-vitro drug dissolution testing displayed enhanced dissolution rate of Silymarin upon loading on MSNs. High dose Acetaminophen was then used to inflict hepatic injury upon albino male Wistar rats simultaneously receiving either free Silymarin, Silymarin loaded MSNs or blank MSNs. Plasma AST, ALT, albumin and total protein and liver homogenate content of TBARs or LDH as measures of antioxidant drug action were assessed for all animal groups. Results showed a significant superiority of Silymarin loaded MSNs to free drug in almost all parameters. Meanwhile prolonged administration of blank MSNs had no evident toxicity on rats.

Keywords: mesoporous silica nanoparticles, safety, solubility enhancement, silymarin

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Authors: Bukola Tola Aluko, Omotade Ibidun Oloyede

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Ocimum americanum L. (Lamiaceae) is an annual herb that is native to tropical Africa. The in vitro and in vivo antioxidant activity of its aqueous extract was carefully investigated by assessing the DPPH radical scavenging activity, ABTS radical scavenging activity and hydrogen peroxide radical scavenging activity. The reducing power, total phenol, total flavonoids and flavonols content of the extract were also evaluated. The data obtained revealed that the extract is rich in polyphenolic compounds and scavenged the radicals in a concentration-dependent manner. This was done in comparison with the standard antioxidants such as BHT and Vitamin C. Also, the induction of oxidative damage with paracetamol (2000 mg/kg) resulted in the elevation of lipid peroxides and significant (P < 0.05) decrease in activities of superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase in the liver and kidney of rats. However, the pretreatment of rats with aqueous extract of O. americanum leaves (200 and 400 mg/kg), and silymarin (100 mg/kg) caused a significant (P < 0.05) reduction in the values of lipid peroxides and restored the levels of antioxidant parameters in these organs. These findings suggest that the leaves of O. americanum have potent antioxidant properties which may be responsible for its acclaimed folkloric uses.

Keywords: antioxidants, free radicals, ocimum americanum, scavenging activity

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Authors: Zahra Tolou-Ghamari

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Introduction: After allogeneic organ transplantation, in order to lower the rate of rejectiontacrolimus is given. In fact, infection is reported as the most complication of tacrolimus that might be associated with higher susceptibility by its’ long term use. Aim: This study aims to review the association between the occurrence of infections after organ transplantation following the administration of tacrolims. Materials and Methods: Scientific literature on the pharmacotherapy of tacrolimus after organ transplantation and infections were searched using PUBMED.Gov (https://pubmed.ncbi.nlm.nih.gov/), Web of Science, and Scopus. Results: In order to prevent acute and chronic rejection, the potent immunosuppressive drug tacrolimus administered as a calcineurin inhibitor after organ transplantation. Its’ most frequent infectious complication is reported as urinary tract infection. Virulent strain of recombinant Literiamonocytogenes, in addition to an increase in bacterial burden in the liver and spleen tissues, was reported in the animal experimental study. The consequence of aggressive events and recipients total area under the cureve exposure to immunosuppressive could be as considered as surrogate markers for individual infection’s risk evaluation. Conclusion: Transplant surgery and duration of hospital stay could determinate the risk of infection during the first month of organ transplantation. Despite administration of antiviral drugs, opportunistic infection such as cytomegalovirus could increase the risk of infection during month 1 to year after transplantation.

Keywords: transplant, infection, tacrolimus, kidney

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Authors: Lee Seungheon, Kim Ba-Ro

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In this study, the anti-stress effects of the ethanolic extract of Hydrangeae Dulcis Folium (EHDF) were investigated. To determine the effects of EHDF on physical stress, changes in the whole-body cortisol level and behaviour were monitored in zebrafish. To induce physical stress, we used the net handling stress (NHS). Fish were treated with EHDF for 6 min before they were exposed to stress, and the fish were either evaluated via behavioural tests, including a novel tank test and an open field test or sacrificed to collect body fluid from the whole body. The results indicate that increased anxiety-like behaviours in the novel tank test and open field test under stress were recovered by treatment with EHDF at 5, 10 and 20 mg/L (P < 0.05). Moreover, compared with the normal group, which was not treated with NHS, the whole-body cortisol level was significantly increased by treatment with NHS in the control group. Compared with the control group, pre-treatment with EHDF at concentrations of 5, 10 and 20 mg/L for 6 min significantly prevented the increase in the whole-body cortisol level induced by NHS (P < 0.05). In addition, adrenocorticotropin hormone (ACTH) challenge studies showed that EHDF completely blocked the effects of ACTH (0.2 IU/g, IP) on cortisol secretion. These results suggest that EHDF may be a good anti-stress candidate and that its mechanism of action may be related to its positive effects on cortisol release.

Keywords: net handling stress, zebrafish, hydrangeae dulcis folium, whole-body cortisol, novel tank test, open field test

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Authors: Mallem Leila, Aiche Mohamed Amine, Boulakoud Mohamed Salah

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A number of chemical compounds are being used to protect agricultural crops from diseases. Residues of these chemicals lead to environmental pollution and pose some threat to non target organisms, human and animal. The aim of this study is to detect the toxicity of these fungicides and their mixtures in the fertility and biochemical’s parameters in the rat. The male of rats (28) were used, they were divided in four groups (7 rats of each group) and one group was used as control. Rats were dosed orally with propiconazole (60 mg/kg body weight/day), propinebe (100 mg/Kg body weight/day) and their mixture (50:50) for 4 weeks. Animals were observed for clinical toxicity. At the end of treatment period, animals of all groups were scarified and samples of different organs were fixed in the formol 10% for histopathological study, and blood was collected for hematological and biochemical’s analysis. The results indicated that the fungicide and their mixture of fungicides were toxic in the treated animals. The semen study showed a decrease in the count, mobility and speed of spermatozoa in all treated group especially those dosed with the mixture and Propiconazole, it was also a decrease in the weight of the testis and epidydimis in the treated group as compared with control. Remarquable histological changes were observed in the testis and epidydimis and liver in the group treated with mixture.

Keywords: fungicides, mixture, fertility, hematological, biochemical's parameters

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Authors: Min-Ju Jo, Min-Young Um, Moonsung Choi, Sooim Shin

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Type 2 diabetes (T2D) is characterized by insulin resistance, the inability of β-cell and the dysfunction of mitochondria. To characterize effects of Cassia tora extract on mitochondrial dysfunction related T2D, the reduced glutathione level, amount of mitochondrial complexes and activities of mitochondrial complexes were measured. Three groups of mice were modeled; a control group was fed a normal diet, a diabetic group was fed a diabetic diet high in fat and carbohydrates, and a third group was fed a diabetic diet + 70% ethanol extracted Cassia tora seeds for 12 weeks. The amount of mitochondria was determined by Bradford assay after isolation of mitochondria in liver from each group. During isolation of mitochondria, cytosolic fractions of the tissue were collected to measure the reduced glutathione level. Interestingly, high level of the reduced glutathione was observed in Cassia tora treated group and decreased activities of mitochondrial complexes in Cassia tora treated group compared to the diabetic diet group. It indicates that Cassia tora has the potential to increase the reduced form of glutathione functioned as an important antioxidant in cells, and to reduce mitochondrial metabolic compensatory mechanism.

Keywords: antioxidant, Cassia tora, diabetes, electron transport chain, glutathione, mitochondria, spectrophotometry

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