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Aug 2025 DOI 10.14302/issn.3070-1937.ijbt-25-5408
Background and Objectives Platelets are small, anucleate blood cells produced in the bone marrow, primarily involved in blood coagulation. Platelet concentrate is a vital blood product with extensive applications. However, its short lifespan and limited donor availability pose global challenges. This study aimed to follow the trend of platelets 5 during days of storage. Material and Methods We studied on 40 platelet bags and analyzed glucose levels, lactate dehydrogenase (LDH), bacterial culture, and apoptosis using flow cytometry with Annexin V-PI over three consecutive days (first, third, and fifth) post-blood collection. Data were analyzed using SPSS. Results No significant correlations were found between age, blood group, or gender and the variables studied. No bacterial growth was detected. Glucose levels decreased significantly from day 1 (382 mg/dl) to day 5 (298 mg/dl). The average platelet apoptosis increased significantly from 3.65% on day 1 to 9.06% on day 5. Significant correlations were observed between glucose levels and apoptosis on days 3 (p<0.05) and 5 (p<0.01). No correlation found between LDH and apoptosis or necrosis, although a significant relationship between necrosis and apoptosis was noted on day 5 (p=0.003). Conclusion These findings suggest that while demographic factors do not influence the studied variables, the significant decrease in glucose levels correlates with increased platelet apoptosis over time, highlighting potential metabolic interactions that warrant further investigation. Highlights 1. The study revealed subtle variations in metabolic markers related to donor demographics, particularly gender and age. Understanding these differences can inform targeted donor selection strategies to optimize platelet quality. 2. A significant negative correlation was found between glucose levels and apoptosis rates, indicating that as glucose decreases, platelet viability declines. This relationship highlights the need for careful monitoring of glucose levels during storage to maintain platelet function. 3. Fluctuations in lactate dehydrogenase (LDH) levels were correlated with increasing rates of apoptosis, suggesting that LDH could serve as a valuable biomarker for assessing platelet quality throughout the storage period. This finding could lead to improved storage protocols and enhanced transfusion safety.
Mar 2018 DOI 10.14302/issn.2575-1212.jvhc-18-2013
Lipopolysaccharide (LPS) is a component of the outer membrane of gram negative bacteria. LPS challenging allows switching transcription of proinflammatory cytokines on via over stimulation of Toll-like receptors (TLRs) signaling pathway with subsequent pathogenic inflammatory response. We investigated the possible reproductive toxicity of LPS in male Wister albino rats. Oxidative stress markers, antioxidant status and caspase-3 activity were analyzed in testicular tissues of rats exposed to either saline or LPS (4 mg/kg BW, ip; 0.18 of the LD50). The samples were collected at 6 h and 72 h after injection of LPS. A significant reduction in testicular reduced glutathione (GSH), glutathione-S-transferase (GST) and superoxide dismutase (SOD) was observed at 72 h compared to control group. Total antioxidant capacity was decreased at 6 h with additional significant reduction at 72 h. Catalase activity was reduced significantly at both 6 and 72 h. Malondialdehyde (MDA) was increased (P ≤ 0.05) in LPS injected rats without variation between 6 and 72 h. A significant increase in nitric oxide (NO) was observed at 72 h after injection. A time-dependent increase in LPS-treated groups was observed in the concentration of caspase-3.Histopathological analysis revealed degenerative changes and necrosis of seminiferous tubules after 6 h with further accumulation of eosinophilic edematous transudate in its lumen after 72 h. In conclusion, by increasing time of exposure, LPS induced lipid peroxidation, oxidative stress, reduced testicular antioxidant capacity and encouraged testicular apoptosis which could be possible mechanisms for impairment of testicular function.
May 2015 DOI 10.14302/issn.2471-7061.jcrc-14-574
Colon cancer has a five-year survival of 64.7%, and about 50,000 people are expected to die from colon cancer this year. Patients with metastatic colorectal cancer have a significantly worse prognosis, a 12.9% five-year survival. This emphasizes the need for strategies to inhibit the growth and metastases of colorectal cancer. Prostate apoptosis response protein 4 (Par-4) is a pro-apoptotic protein that has been shown to mediate apoptosis in response to stimuli, such as chemotherapeutics and radiation. Recombinant Par-4 protein has been shown to reduce the occurrence of Lewis lung carcinoma metastases in-vivo; however, the mechanism by which Par-4 can inhibit metastasis has not been elucidated. In this study, human colon cancer cell lines - SW480 and SW620 - were transfected with Par-4 plasmid or anti-Par-4 shRNA, and the effect on metastasis was examined. Par-4 overexpression inhibited cell migration and invasion, while Par-4 knockdown promoted it. Moreover, the morphology of SW620 cells was altered when Par-4 levels were increased. The change was characteristic of a mesenchymal-to-epithelial transition (MET) in these cells. MET can be induced by upregulation of E-cadherin expression, and RT-PCR and Western blot analyses showed that E-cadherin mRNA and protein levels, respectively, were increased in the Par-4 overexpressing cells concomitant with a decrease in vimentin. The results of this study demonstrate the potential of Par-4 in colon cancer therapy, not only in primary tumors but also in metastatic cells.
Dec 2014 DOI 10.14302/issn.2326-0793.jpgr-14-598
Colorectal cancer is one of the most commonly diagnosed cancers worldwide and its prevalence can be reduced by changes to lifestyle and diet. Fermentation of dietary fibre by the gut microbiota and formation of short chain fatty acids, in particular butyrate, is widely thought to play a role in preventing development of the disease. Despite butyrate’s known pro-apoptotic effects, a subpopulation of cancer cells is able to overcome these anti-neoplastic effects of colonic luminal butyrate to proliferate and establish tumours in vivo. In this study, a time course analysis of HT29 and HT29-BR cells treated with butyrate was conducted and global gene expression analysis was used to identify novel mechanisms associated with butyrate-induced apoptosis and in the acquisition of butyrate resistance. Bioinformatic analysis of the data identified deregulated O-GlcNAcylation activity and disruption to gene transcription by BRD4 as possible factors involved with butyrate-induced apoptosis. EGF signalling was identified as being potentially involved in the acquisition of butyrate resistance. Furthermore, the expression of the minichromosome maintenance protein family was significantly reduced in the HT29-BR cell line reflecting disruptions to the DNA replication process. Together, this may confer a unique survival advantage for cells with acquired butyrate resistance.
Dec 2025 DOI 10.14302/issn.2575-1212.jvhc-24-4889
L-Carnitine (Lc) acts as an antioxidant that neutralizes free radicals, especially superoxide anions and protects cells against oxidative damage-induced apoptosis, as following ovulation, intracellular reactive oxygen species (ROS) accumulation increases in oocytes, Oocytes exhibit an intracellular defense mechanism against an oxidative attack. This outcome adversely affects fertilization and subsequent embryonic development, thereby increasing the risk of an early miscarriage and abnormal development of offspring. The purpose of this study was to see how adding LC to either maturation or fertilization medium affected the developmental competence of immature bovine oocytes. In this study, Ovaries from apparently normal reproductive organs of cattle were collected within 30 minutes from slaughter and evisceration of animals. Cumulus oocyte complexes (COCs) were collected by aspiration of medium sized ovarian follicles (4-8 mm). COCs of acceptable quality were selected, washed and incubated in tissue culture media 199 (TCM199) supplemented with 10% heat inactivated fetal calf serum, 5 μg/ml luteinizing hormone (LH), 0.5 μg/ml follicle stimulating hormone (FSH) and 1 μg/ml estradiol-17β for 20:22 hour at 38.5 C◦ under 5% CO2 in air with 90% humidity. different concentrations of LC (1.25,2.5 and 5mM) were used. The results were consistent for both maturation and fertilization and there is a significant increase in maturation, fertilization., cleavage and blastocyst rate. In conclusion, LC has important role in IVEP through addition of LC to maturation media or culture media it improved nuclear maturation and blastocyst formation rates in bovine oocytes.
Dec 2025
The incidence rate of melasma is notably high among patients with anxiety disorders. Aromatherapy primarily influences the physiological and psychological states of individuals through the inhalation or application of essential oils, thereby facilitating the treatment or alleviation of various conditions. This study aims to explore the action mechanism of complex lemon-angelica sinensis -boswellia essential oil (CEO) in treating anxiety disorders with melasma. We investigated the active ingredients, targets, and pathways of CEO in relation to anxiety and melasma using network pharmacology. We employed cell assays and conducted nebulized essential oil inhalation tests on CUMS mice to validate the intervention effects of CEO on anxiety. A total of 28 active components, including neryl acetate, 3-butenylphthalide and octyl acetate, and 26 cross-targets, such as ESR1, CCND1 and PIK3CA, were identified. GO and KEGG pathway analyses indicated that these cross-targets were primarily involved in endocrine regulation, cell proliferation, and apoptosis, specifically through PI3K/Akt signaling pathway and calcium signaling pathway. The experimental results demonstrated that CEO significantly reduced the secretion of NO, TNF-a and IL-6, as well as the mRNA expressions of ESR1, CCND1 and PIK3CA in cells compared to the inflammatory cell model. Furthermore, CEO notably decreased the forced swimming immobility time of mice and the levels of IL-1β, ESR1 and CCND1 in hippocampus when compared to model mice. These findings suggest that CEO may regulate ESR1, CCND1 and PIK3CA through its citral, 3-butylphthalate and neryl acetate, thereby influencing endocrine function, cell proliferation and apoptosis, inhibiting inflammation and anxiety-like behavior in CUMS-induced mice.
Jun 2022 DOI 10.14302/issn.2641-4538.jphi-22-4197
Aim and Objective Despite the growing concerns about the relationship between exposure to radiofrequency radiation (RFR) and detrimental health effects due to the changes in biological processes of experimental animals, there is still ongoing debate on the significance of these findings in causing significant public health problems with the growing advancement in internet technology. The aim of this study is to review existing literature on the effects of high RFR on wistar rats. Method A search was conducted on Google scholar and PubMed to identify relevant peer-reviewed articles to be included into the review. Studies eligible for inclusion included free full text articles on wistar rats exposed to ≥ 2.45GHz RFR conducted in the past 5 years. Studies included in this review were written or transcribed in English language. From 286 titles, 36 eligible studies were included in the review and assessed for quality using the Strengthening the Report of Observational Studies in Epidemiology – Veterinary Extension (STROBE-Vet) quality assessment tool. Results Studies included in this review generally had good quality (>60%) based on the STROBE-Vet assessment. This review identified numerous biological changes in wistar rats exposed to high RFR including variations in biochemical, cholinergic, genetic, histopathologic, psychological, optical, and dermatological parameters. In this review, studies identified variations in protein and liver enzymes while high RFR was found to induce oxidative stress and cellular damage of exposed wistar rats compared to the unexposed groups. This was seen in the changes in protein, lipids, enzymatic and non-enzymatic antioxidants. Studies also identified changes in expression of genes and neurotransmitters with imbalance in hormones. In addition, this review identified structural changes of cells, tissues and organs indicative of apoptosis, damage and death. Exposed rats were identified to have behavioral changes indicative of anxiety and memory decline while studies identified optical and dermatologic changes in exposed rats compared to the unexposed. Conclusion With numerous biological changes identified in wistar rats exposed to high RFR, there is an increasing risk of detrimental health events giving the advancement in internet technology and limited regulations to control exposures to RFR. Therefore, studies should be conducted to identify strategies to mitigate human exposure to RFR while policies are developed and enforced to protect human health.
Aug 2021 DOI 10.14302/issn.2471-2140.jaa-21-3910
Oxidative stress is implicated in male infertility and significantly higher reactive oxygen Species (ROS) are detected in 25% of infertile males. We showed that Ozone oxygen therapy (O2/O3) induces protective effects for oxidative stress factors and its consequences on isolated mitochondria obtained sperm which may provide insight into the role of Ozone oxygen in human infertility. The present study was carried out to further characterize and compare protective effect of Ozone oxygen on isolated mitochondria obtained from sperm. Semen was collected from human normal donors. We gained human sperm mitochondria by differential centrifugation and isolated mitochondria incubated with different concentrations (5µg/ml, 30 µg/ml, 80 µg/ml) of O2/O3. O2/O3 prevent significant decrease in reactive oxygen species formation and mitochondrial membrane potential collapse on isolated Human sperm mitochondria. Ozone oxygen therapy induced increase in ATP concentration on isolated mitochondria. Our findings showed that O2/O3 prevent toxicity in sperm, effect on mitochondrial respiratory chain and avoid to cytochrome c release and apoptosis signaling.
Sep 2020 DOI 10.14302/issn.2576-6694.jbbs-20-3525
The photosynthetic potential and underlying internal metabolism of a plant are some of the most commonly affected physiological functions as a direct consequence of stresses due to salt and water resulting in hindering plant growth and productivity. Under the influence of such detrimental stresses, a drastic alteration in a plant's osmotic requirements, hormonal production, shedding of leaves, and closure of stomata, along with a lessening in the diffusion and transportation of CO2 and H2O are commonly seen. This review unfolds with a description of the basic methodology involved in the proteomic analysis of various proteins involved in stress response along with a brief idea on identifying and obtaining a genomic sequence for proteomic studies. It then dives deep into understanding the impact of abiotic stresses such as salinity, drought and high temperatures on cereal crops such as rice and sorghum as well as the internal dynamics of tolerance mechanism unfolding during stresses have also been described. Extensive literature describing the proteomic and physiological responses to primary and secondary effects of salt stress in cereal crops emphasizing on ROS production and apoptosis, the role of osmolytes as ROS scavengers during osmotic stress and vacuolar antiporters in ionic stress along with the responses during drought stress such as the accumulation of LEA proteins and ABA-based signaling has been reviewed and critically discussed. The study also sheds light on some experimental proteomic studies conducted on the seedlings, root tissues, and shoots of rice cultivars.
Aug 2020 DOI 10.14302/issn.2641-7669.ject-20-3529
Background Local anesthetic neurotoxicity is a common complication in clinical anesthesia, which can cause permanent nerve damage in severe cases. The T-type calcium channel is an important channel for regulating the excitability of neurons. Normally, extracellular calcium ions enter the cell through the T-type calcium channel to change the excitability of neurons. When the intracellular calcium is overloaded, it can cause cell damage. Aims To investigated the roles of T-type calcium channel in the SH-SY5Y cells injury induced by the bupivacaine. Methods The SH-SY5Y cell culture model was used to observe the effect of T-type calcium channel blocker NNC55-0396 on the neurotoxicity of bupivacaine hydrochloride by MTT methold,flow cytometry, Western blotting and other methods. Results The results show that NNC55-0396 can block the T-type calcium channel of SH-SY5Y cells, improve the decrease of cell viability caused by bupivacaine hydrochloride, reduce the level of intracellular calcium ion, reduce the expression of Cleavedcaspase-3, and reduce cell apoptosis. Conclusion The above results indicate that the T-type calcium channel is involved in the SH-SY5Y cell damage caused by bupivacaine hydrochloride, and blocking the T-type calcium channel can reduce the neurotoxicity of bupivacaine hydrochloride.
Apr 2020 DOI 10.14302/issn.2832-4048.jsm-20-3211
Aging mammalian skeletal muscle satellite cells (MuSCs) undergo a decline of stem cell/progenitor cell proliferative and regenerative capacity, and the development of a physiological milieu characteristic of a state of chronic sterile inflammation. p38αMAPK and ERK1/2 are two major signaling pathways that regulate the age-associated decline of MuSC proliferative capacity. In this review we propose the following mechanism that links the p38αMAPK pathway to the decline of self-renewal and regenerative capacity of aged MuSCs: a) the HS-FGF-2-FGFR1-p38αMAPK-Axis, a tightly linked homeostatic signaling complex, is in synchrony with the autoinhibition of FGFR1; b) autoinhibition contributes to the Axis’ regulation of the homeostasis of P-p38αMAPK activity in juvenile MuSC; c) this combination of protein-protein interactions is characteristic of a juvenile cytoplasmic milieu of beneficial P-p38αMAPK activity and d) includes Sprouty1 inhibition that supports the stimulation of FGF-2 --> miR-29a; e) the miR29a dismantles the basement membrane in preparation for the initiation of replication; f) an age-associated impaired, dysregulated, over-sulfated heparan sulfate ligand (HS)-FGF-2 fails to activate FGFR1 in aged MuSCs; g) this uncouples its regulation of p38αMAPK and ERK1/2 pathways and results in desensitization of FGFR1; h) desensitization of FGFR1 and Sprouty1 interaction in aged MuSC uncouples their regulation of P-p38αMAPK in the aged MuSCs; i) this enables a state of chronic sterile inflammation to promote and sustain an increased level of P-p38αMAPK activity; and, j) the increased activity of P-p38αMAPK in aged MuSC stimulates the production of cell cycle inhibitors, miR-1 and miR-133, thereby attenuating the expression of the cell cycle regulators, SP1 and cyclin D1, resulting in a G1/S arrest; j) the increased level of p38αMAPK activity promotes the apoptosis of the aged activated MuSCs. This mechanism involves the synergistic interactions of HS-FGF2-FGFR-1, Sprouty (spry1), miR-1, miR-133 and miR-29a that unify the extracellular niche and intracellular milieu for the juvenile vs age-associated regulation of proliferative capacity of the MuSC. Our hypothesis unifies these interactions with the role of the extracellular niche and intracellular milieu in the stimulation of juvenile proliferation vs age-associated decline of skeletal muscle satellite cell self-renewal and regenerative proliferation. Word Count = 344
Jan 2020 DOI 10.14302/issn.2379-7835.ijn-20-3159
Pyruvate holds superior biomedical properties in increase of hypoxia tolerance, correction of severe acidosis, exertion of anti-oxidative stress and protection of mitochondria against apoptosis, so that it improves multi-organ function in various pathogenic insults. Particularly, pyruvate preserves key enzyme: pyruvate dehydrogenase (PDH) activity through direct inhibition of pyruvate dehydrogenase kinas (PDK), as a PDH activator, in hypoxia. Therefore, pyruvate is robustly beneficial for cell/organ function over citrate, acetate, lactate, bicarbonate and chloride as anions in current medical fluids. Pyruvate-enriched oral rehydration salt/solution (Pyr-ORS) and pyruvate-based intravenous (IV) fluids would be more beneficial than WHO-ORS and current IV fluids in both crystalloids and colloids, respectively. Pyruvate-containing fluids as the new generation would be not only a volume expander, but also a therapeutic agent simultaneously in fluid resuscitation in critical care patients. Pyruvate may be also beneficial in prevent and treatment of diabetes, aging and even cancer. Pyruvate clinical applications indicates a new revolutionary medical advance, following the WHO-ORS prevalence, this century.
Aug 2019 DOI 10.14302/issn.2572-3030.jcgb-19-2973
Head and Neck cancer (HNC) is one of the most prevalent and lethal cancer globally. The incidence of tobacco-induced HNC is gradually increasing in low and middle income countries. Among the various causative factors associated with HNCs, tobacco and alcohol play synergistic effect and are frequently associated with the risk of HNC. Tobacco-induced HNCs show distinct genetic and epigenetic alterations leading to different clinical outcomes in comparison to HPV-infected HNCs. Tobacco-induced HNCs are often associated with tumor aggressiveness, poor prognosis and low or nil prevalence of HPV infection. Apart from carcinogenic effects of these causative factors (use of tobacco products, alcohol intake and HPV or EBV infections), recent studies show that exposure to these factors alter/disrupt the regulation of non-coding RNAs including the long non-coding RNAs (lncRNAs). Altered lncRNA regulation is brought about by signalling networks that regulate cellular differentiation, apoptosis, angiogenesis and inflammatory pathways which play key functions in the genesis of different cancers including HNCs. There are numbers of studies supporting the emerging role of lncRNAs in development of HNC; however, reports connecting lncRNAs expression and addiction habits in HNC are still preliminary and sparse. Therefore, identification and characterization of lncRNAs that are differentially expressed upon exposure to risk-factors can serve as unique therapeutic targets and potential biomarker(s) for effective treatment of HNC subtypes. In this short review, we briefly reviewed the emerging role of lncRNAs in tobacco and alcohol induced HNCs.
Apr 2019 DOI 10.14302/issn.2328-0182.japst-19-2759
Cancer is the leading cause of death worldwide, and there is a constant need for new treatment strategies. Sesquiterpene lactones containing a 3-methylenedihydrofuran-2(3H)-one (or α-methylene-γ-lactone) moiety, for example damsin (1), are Michael acceptors that affect biological processes such as cell proliferation, death/apoptosis, and cell migration, by interfering with cell signalling pathways. Although the reactivity of the α-methylene-γ-lactone moiety is important for these effects, the Michael addition is reversible and it can be assumed that also other parts of the molecules will moderate any given biological activity. In this investigation, the cytotoxicity of 23 -methylene--lactones towards normal breast epithelial MCF-10A cells as well as breast cancer JIMT-1 cells is compared. Most of the investigated compounds are semisynthetic derivatives prepared by the condensation of the natural product damsin (1) with aldehydes. The two cell lines were treated with various concentrations of the compounds in dose response assays, and the 50 % inhibitory concentration (IC50) was determined from dose response curves. The IC50 values were found to depend strongly on the overall structure. The ratio between the IC50 values for MCF-10A and JIMT-1 cells, as a measure for the selectivity of a compound to kill cancer cells, was calculated, and found to vary between just over 1 to more than 10. The most potent derivatives formed from the condensation of 1 with aromatic aldehydes towards JIMT-1 cells are 3a and 3i, both with ratios between the IC50 values for MCF-10A and JIMT-1 cells close to 5. Also some aldol condensation products with acyclic aldehydes, i.e. 3r and 3u, were equally potent, and the latter showed the highest selectivity (ratio > 10). Structure-activity relationships that may explain the observed differences in potency and selectivity are discussed.
Feb 2019 DOI 10.14302/issn.2377-2549.jndc-18-2569
Anthraquinones is a potent aromatic compound that besides being used commercially it offers numerous therapeutic benefits such as inhibits cancer growth by inducing apoptosis, relive constipation, ease bowl movement etc. Anthraquinones are found naturally in some plants such as senna, buckthorn, yellow dock etc while it can also be produced using chemical routes such as anthracene oxidation, naphthalene oxidation, condensation of 1, 4-naphthoquinone with butadiene etc. However its intake should strictly be regulated since it may cause some serious side effects.
Aug 2018 DOI 10.14302/issn.2377-2549.jndc-18-2116
Silver nanoparticles (Ag-NPs) are versatile materials with a broad range of applications in various fields such as cancer therapy, drug delivery. In this work, cytotoxic and apoptotic activities of silver nanoparticles was evaluation against lung (A549) and colon (HT-29) cell lines. The cytotoxic activity of nanoparticles was performed by MTT assay, while their apoptotic activity was tested through TUNEL method. The results of MTT of A549 have illustrate that fifty percent of cells destruction in concentrations more than 250 µg/ml of Ag-NPs. Apoptotic results of nanoparticles have shown more than fifty percent of apoptosis on A549 cell line. HT-29 display full apoptosis at concentrations more than 500 µg/ml. It seems that synthesized Ag-NPs by using P. farcta extract can be candidate as anti-cancer agent in treatment many cancers through creating or discovering new drug forms
Dec 2017 DOI 10.14302/issn.2766-8630.jrnm-17-1770
The aims of this study are to investigate the variation in the mechanical behaviour of the primary cancer from cancer relapse, and measuring the therapeutic resistance acquired by cancer relapse. A431-cultured cells were irradiated for 7 months until 85 Gy. Then, a selected single cell was left to grow as stable A431-R cell line. 106 cells of A431 cells and 106 of A431-R cells suspended in 100 μL of medium were injected into subcutaneous tissues on the right thigh of athymic mice to generate tumor xenografts models of primary cancer (A431-P) and cancer relapse (A431-R). Radiotherapy of a low-dose of 30Gy was applied on xenoimplanted tumors after one week from inoculation. A mock process was performed on untreated groups of mice for controls. Tumor size was monitored starting from inoculation and tumor growth was measured along 42 days. Rates of mitosis and apoptosis and the histologic grade (HG) that characterize the tumor response were determined as described in earlier studies. Alterations induced on tumor HG in the treated models were 100% identical to the energy of the applied doses. The differences in response energy between cancer relapse and primary cancer irrespectively of the treatment (untreated vs. treated) or origin of the cells (A431-P vs. A431-R) in all phases of tumor responses (growth, shrinkage or regrowth) were 100% identical to the total differences in the administered regimens applied on those groups during those phases. Cancer relapse is characterized by a delay in growth before second line therapy for its relatively lower rate of mitosis compared by the primary cancer inducing a corresponding delay in the early detection. The therapeutic resistance of the cancer relapse is equivalent to the energy of the doses which have been delivered in the prior therapies, and requires increasing the administered dose by an amount equivalent to that resistance.
Dec 2017 DOI 10.14302/issn.2641-7669.ject-17-1789
We aimed to study the effect of buspirone, an anxiolytic drug and 5-HT1A agonist on liver injury induced by carbon tetrachloride (CCl4) in rats. Rats were orally treated with CCl4 (2.8 mL/kg in olive oil) along with buspirone at 10, 20 or 30 mg/kg once daily starting with CCl4 and for one week thereafter. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as alkaline phosphatase (ALP) activities were determined in the serum. Markers of oxidative stress: lipid peroxidation (malondialdehyde; MDA), reduced glutathione (GSH), nitric oxide (nitrite/nitrate) levels were measured in the liver. Moreover, paraoxonase 1 activity was determined in the liver and serum. The administration of CCl4 led to significant increases in serum ALT, AST, and ALP activities. Results showed that there were significantly increased hepatic MDA, nitrite and decreased GSH levels. PON1 activity decreased both in the liver and serum, respectively. The immunohistochemical investigations using anti-caspase-3 antibody revealed that CCl4 caused apoptosis to many hepatocytes. DNA studies showed that CCl4 caused hypoploidy in hepatocytes. Rats treated with 20-30 mg/kg buspirone showed significant decrease in serum ALT and AST by 19.5-34.3% and 24.2-31.4%, respectively. Serum ALP decreased by 21.7% after 30 mg/kg buspirone. In the liver, the higher dose of the drug resulted in decreased MDA (by 15.8%), decreased nitric oxide (17.4%) and increased GSH (by 20.1%). Significantly increased serum PON1 activity by 43.9-53.5% was observed after treatment with 20-30 mg/kg buspirone. On histopathologic examination of liver sections, there was mild protective effect for the drug at 30 mg/kg. Sections stained with anti- caspase- 3 confirmed the results obtained from histopathological examination. Moreover, buspirone given at 30 mg/kg resulted in an increase in % of cells containing normal values of DNA. These results indicate that buspirone decreases liver oxidative stress and exerts protective effect against CCl4- toxicity. The study thus indicates more beneficial effects of buspirone as an anxiolytic drug and that the drug could be used safely in patients with liver disease.
Jul 2017 DOI 10.14302/issn.2326-0793.JPGR-17-1571
Perkinsus marinus is an intracellular parasitic protozoan that is responsible for serious disease epizootics in marine bivalve mollusks worldwide. Despite all available information on P. marinus genomics, more baseline data is required at the proteomic level. Our aim was to study the proteome profile of in vitro cultured P. marinus isolated from oysters Crassostrea spp. using a label-free shotgun UDMSE approach. A total of 4073 non-redundant proteins were identified across three biological replicates with stringent identification. Proteins specifically related to adaptive survival, cell recognition, antioxidants, regulation of apoptosis and others were detected. Important virulence factors of P. marinus were identified including serine protease and iron-dependent superoxide dismutase. Other proteins with involvement in several pathogens invasion strategies were rhoptries, serine-threonine kinases, and protein phosphatases. Interestingly, peptides corresponding to retroviruses polyproteins were identified in all replicates. The interactomic analysis of P. marinus proteins demonstrated extensive clusters network related to biological processes. In conclusion, we provide the first comprehensive proteomic profile of P. marinus that can be useful for further investigations on Perkinsus biology and virulence mechanisms.
Feb 2016 DOI 10.14302/issn.2572-5424.jgm-15-815
Background: Polymorphonuclear leucocytes are the first line of defence against foreign invaders and constitute the major cell type involved in certain types of acute and chronic inflammatory diseases. Aim of the Work: The aim of the present study was to investigate the changes in expression of BCL-2 and BAK genes by real time PCR and to study whether they were involved in the accelerated neutrophil apoptosis which might be responsible for the recurrent bacterial infections seen in chronic renal disease and hemodialysis patients. Subjects and Methods: This study was conducted on sixty two subjects. Patients were selected from those admitted to Theodor Bilharz Research Institute (TBRI). Patients under study were classified into three groups; CKD patients (group I) kept on conservative treatment (22 cases), ESRD patients (group II) maintained on dialysis therapy, HD (20 cases). In addition, twenty healthy individuals served as a control group (group III) were involved. Results: There was significant increase in level of BAK gene in both patients' groups compared to control group with more increase in CKD group than ESRD group. Significant difference between the 3 groups was encountered with a higher expression level in CKD and ESRD groups than controls. There was decrease in level of BCL2 gene in both groups less than control group with more declines in ESRD group than CKD group. Conclusion: Bcl2 and Bak genes could have a role in survival and apoptosis of the studied groups and suggested their impact in controlling the inflammatory mechanisms and eventually their therapeutic potential.
Dec 2015 DOI 10.14302/issn.2471-2140.jaa-15-765
Reactive oxygen species (ROS) and reactive nitrogen species are believed to be one of the most important culprits in the pathogenesis of cardio/cerebrovascular diseases. Intensive researches have been conducted to target free radicals as potential treatment for cardio/cerebrovascular diseases. The 2-(((1,1-dimethylethyl) oxidoimino)-methyl)-3,5,6-trimethylpyrazine (TBN), a novel nitrone derivative of tetramethylpyrazine, has been demonstrated to exhibit significant therapeutic effects in ischemic stroke and Parkinson’s models due to its multiple functions, including calcium overload blockade and free radical-scavenging activity. In the present study, we found that TBN had significant radical trapping effect in cell-free assays. Additionally, TBN effectively blocked tert-butylhydroperoxide (t-BHP)-induced murine H9c2 cardiomyoblast cell death, suppressed H9c2 cell apoptosis and reversed the decrease in mitochondrial membrane potential. Furthermore, TBN markedly inhibited t-BHP-induced ROS generation and free radical NO and ONOO–.Taken together, these results suggest that TBN might be a potential candidate for the treatment of ischemic cardio/cerebrovascular diseases by targeting free radicals.
Feb 2014 DOI 10.14302/issn.2372-6601.jhor-13-358
Acute lymphoblastic leukemia (ALL) is a rapid form of leukemia characterized by clonal proliferation and accumulation of immature hematopoietic stem cells of the lymphoid lineage in the bone marrow as well as peripheral blood. Chromosomal aberrations identified in childhood ALL have an important role in disease diagnosis, prognosis and management. We present the results of hematologic, immunophenotypic, cytogenetic, FISH and Multiplex RT-PCR analysis of a 6-year-old boy diagnosed with B-cell precursor Acute Lymphoblastic Leukemia (BCP- ALL). In this study, we identified a novel chromosomal translocation t(10;15)(q22;q22) by cytogenetic and FISH analysis. To the best of our knowledge, this is the first report of this novel chromosomal translocation in this subset of ALL and has not yet been reported elsewhere. This rearrangement may include certain cancer associated tumor suppressor gene(s) or genes involved in apoptosis and transcription regulation, which on loss of normal function may lead to leukaemogenesis.