Gallic Acid Inhibits Proliferation and Induces Apoptosis in Lymphoblastic Leukemia Cell Line (C121)

Leukemia is known as the world's fifth most prevalent cancer. New cytotoxic drugs have created considerable progress in the treatment, but side effects are still the important cause of mortality. Plant derivatives have been recently considered as important sources for the treatment of various diseases, including cancer. Gallic acid (GA) is a polyhydroxyphenolic compound with a wide range of biological functions. The aim of the present study was to evaluate the effect of GA on proliferation inhibition and apoptosis induction of a lymphoblastic leukemia cell line. Jurkat cell (C121) line was cultured in RPMI 1640 supplemented with 10% heat-inactivated fetal bovine serum (FBS) with different concentrations of GA (10, 20, 30, 40, 50, 60, 70, 80, 90, and 100 mu M) for 24, 48 and 72 hours. The effect of GA on cell viability was measured using MTS assay. Induction of apoptosis was evaluated with Annexin V-FITC/PI kit and flow cytometry. Data were analyzed by SPSS version 20 using Kruskal-Wallis and Dunn's multiple comparison tests. Decline of cell viability to less than 50% was observed at 60.3+/-1.6, 50.9+/-1.5, and 30.9+/-2.8 mu M concentration after 24, 48, and 72 hours incubation, respectively. All concentrations of GA (10, 30, 50 and 80 mu M) enhanced apoptosis compared to the control (P<0.05). The results demonstrate that the polyphenolic compound, GA, is effective in inhibition of proliferation and induction of apoptosis in Jurkat cell line. It is recommended to study the mechanism of apoptosis induction in future investigations

The effect of gallic acid on Jurkat cell line

Introduction: Acute lymphoblastic leukemia (ALL) is the most prevalent leukemia in children.Fruits and plants have a wide range of biological functions including anti-proliferative effect. Gallicacid (GA), is a polyhydroxyphenolic compound that is widely distributed in the natural plants. Theaim of the present study was the evaluation of the effect of GA on proliferation inhibition of Jurkatcells, the lymphoblastic leukemia cell line.&nbsp;Methods: Jurkat cell line was cultured in blood cells culture media in a standard conditions with&nbsp;different concentrations of GA (0-100 &micro;m) for 24, 48 and 72 hours. The effect of GA on cell viabilitywas measured using MTS assay.Results: Decline of cell viability to less than 50 was observed at 60, 50 and 30 &micro;m concentrationsafter 24, 48 and 72 hours incubation time, respectively.Conclusion: The results demonstrated that the polyphenolic compound, GA with antioxidantcapability is effective in proliferation inhibition in Jurkat lymphoblastic leukemia cell line witha time and dose dependent manner. Therefore, GA may be a potential compound for cancerprevention and treatment

Effect of Epigallocatechin-3-gallate (EGCG) on cell proliferation inhibition and apoptosis induction in lymphoblastic leukemia cell line

Introduction: Acute lymphoblastic leukemia (ALL) is one of the malignant proliferations of lymphoid cells in the early stages of differentiation and accounts for &frac34; of all cases of childhood leukemia. Available treatment cannot completely treat this disease. Epigallocatechin-3-gallate (EGCG) is a polyphenolic compounds in the green tea that has demonstrated to have anticancer and antimitotic properties. The purpose of the present study was the evaluation of the effect of EGCG on the proliferation inhibition and apoptosis induction in a lymphoblastic leukemia cell line. Methods: Jurkat cell line was cultured in standard condition and in different concentrations of EGCG (0-100 micromolar) for 24, 48 and 72 hours. Cell viability was measured by MTS assay. Apoptosis induction was assessed by annexin V-FITC and flow cytometry analysis. Results: The MTS assay revealed that EGCG has decreased cell viability with a time and dose dependent manner. The level of cell apoptosis in all used concentrations of EGCG (50, 70 and 100 &mu;m) was higher than control group (71, 40 and 31 respectively vs. 8) and reached to significant level at 100 &mu;m concentration. Conclusion: The study indicated that EGCG is effective on proliferation inhibition and apoptotic induction in Jurkat lymphoblastic cell line. Therefore, the study of the mechanism of apoptosis induction could be a step of progress toward target therapy which might be considered in the future studies.</p

Lupus and the Nervous System: A Neuroimmunoloigcal Update on Pathogenesis and Management of Systemic Lupus Erythematosus with Focus on Neuropsychiatric SLE

An autoimmune condition is characterized by a misdirected immunological system that interacts with host antigens. Excess activation of T- and B-lymphocytes, autoantibody generation, immune complex deposition, and multi-organ injury are found in systemic lupus erythematosus (SLE), an early autoimmune condition with a substantial hereditary element. A number of environmental factors and lifestyle changes also play a role in the development of SLE. The imbalanced immunity could take part in the dysfunction and injury of different biological organs, including the central and peripheral nervous systems. Neuropsychiatric SLE (NPSLE) can present with focal and diffuse involvements. Clinical manifestations of NPSLE vary from mild cognitive deficits to changed mental status, psychosis, and seizure disorders. Headaches, mood, and cognitive problems are the most common neuropsychiatric presentations associated with SLE. NPSLE could be found in 40% of all people who have SLE. The diagnostic inference of NPSLE can be made solely following these secondary causes have been ruled out. The present chapter provides an updated discussion of the clinical presentation, molecular processes, diagnosis, management, and therapy of SLE with emphasizing on NPSLE

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Interaction between Gallic acid and Asparaginase to potentiate anti-proliferative effect on lymphoblastic leukemia cell line.

Abstract BACKGROUND: Treatment of acute lymphoblastic leukemia (ALL) fails in some cases and the side effects cause mortality in certain patients. Gallic acid (GA), a polyhydroxyphenolic compound has biological functions including anti-proliferative properties. The aim of the present study was to investigate the growth inhibition effects of GA in combination with asparaginase (ASP), as a component of combination chemotherapy, in a lymphoblastic leukemia cell line. METHODS: Jurkat cells were incubated with different concentrations of GA with or without ASP. Proliferation inhibition was investigated using MTS test. The level of apoptosis alterations were evaluated using flow cytometry. The expression of Fas gene level and surface expression were investigated by quantitative real time PCR and flow cytometry respectively. RESULTS: GA at 50μM concentration and ASP at 0.5 IU/ml inhibited 50% cell proliferation in 48 hours. GA also increased the inhibitory effect of ASP and some combinations had synergistic results. The increase of cell apoptosis and Fas expression were observed in GA-treated cells compared to control. GA increased the effect of ASP on proliferation inhibition, induction of apoptosis and Fas expression. CONCLUSION: GA is an effective component in proliferation inhibition, apoptosis induction and enhancement of Fas expression level in Jurkat cell line. GA in some combination with ASP increases the effect of the latter on the cells. The study of the mechanism of these effects could be a further step towards target therapy. This study is a preliminary phase to the use of GA and should be carried out by more comprehensive study and animal models

The effects of hesperetin on apoptosis induction and inhibition of cell proliferation in the prostate cancer PC3 cells

ntroduction: Prostate cancer is the second leading cause of cancer-related deaths and the mostcommon cancer diagnosed in men in the United States and Europe. Hesperetin, a member of thef lavonoids with antioxidant property, is found in fruits such as oranges and red fruits. This study was undertaken to evaluate the effects of hesperetin on apoptosis induction and inhibition of cell proliferation in the prostate cancer PC3 cells.Methods: PC3 cell line was cultured in standard condition. The cells were exposed to differentconcentrations of hesperetin (0-1000 μM) for 48 hours. Cell viability was measured by MTT assay.Apoptosis induction was assessed by Annexin V-FITC by flow cytometry analysis.Results: The PC3 cells exposed to hesperetin (0-1000 μM) exhibited an IC (inhibitoryconcentration of 50%) about 450 μM. At different concentrations of hesperetin (400, 450 and 500µm), the apoptosis increased slightly (not significant) in treated PC3 cells compared to the controlgroup (5.4%, 7.8% and 9.1% respectively vs. 4.2%).Conclusion: These results clearly show that hesperetin can lead to inhibition of PC3 cellsproliferation

Biological effects of hesperetin on Interleukin-6/phosphorylated signal transducer and activator of transcription 3 pathway signaling in prostate cancer PC3 cells

Interleukin-6 (IL-6) is a multifunctional glycoprotein that regulates the growth of some tumors, including prostate carcinomas due to signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated kinases 1/2 (ERK1/2), and AKT signaling pathways. Hesperetin, as a flavanone, has several biological properties such as antitumor and anti-inflammatory. Objective: This study was carried out to evaluate the biological effects of hesperetin on the IL-6 gene expression and phosphorylated STAT3, AKT, and ERK1/2 signaling pathways in PC3 prostate cancer (PC) cells. Materials and Methods: In this study, we used real-Time quantitative polymerase chain reaction (RT-qPCR) and ELISA to evaluate IL-6 gene expression and IL-6 protein secretion, respectively, in the treated PC3 cells with 0, 400, 450, and 500 μM of hesperetin. Cell survival studies were done by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after 48 h treatment with hesperetin, and cell apoptosis was determined by flow cytometry. The protein levels of activated signaling molecules (pSTAT3, pAKT, and pERK1/2) analyzed by immunoprecipitation technique. Results: Hesperetin-Treated PC3 cells resulted in reduction of cell viability. Hesperetin led to the elevation of phosphorylated STAT3, ERK1/2, and AKT signaling proteins after 48 h in a dose-dependent manner as compared to the control cells. IL-6 gene expression, as well as protein level, significantly increased (P < 0.05) in a dose-dependent pattern in treated PC3 with hesperetin compared to the control cells. Further, hesperetin exposure resulted in the induction of cell cycle arrest at G0/G1 phase. Conclusion: Hesperetin in PC3 cells led to elevation IL-6 gene expression, IL-6 protein secretion, pSTAT3, pERK1/2 and pAKT intracellular signaling proteins. Our results indicate that hesperetin treatment leads to the inhibition of cell proliferation and the induction of cell cycle arrest at the G1 phase. Hesperetin can be considered a potent agent which synchronizes and stops cell cycle at G0/G1 phase to apply suitable chemotherapeutic agents and radiotherapy in PC cells

Effect of Epigallocatechin-3-gallate (EGCG) on cell proliferation inhibition and apoptosis induction in lymphoblastic leukemia cell line

Introduction: Acute lymphoblastic leukemia (ALL) is one of the malignant proliferations of lymphoid cells in the early stages of differentiation and accounts for ¾ of all cases of childhood leukemia. Available treatment cannot completely treat this disease. Epigallocatechin-3-gallate (EGCG) is a polyphenolic compounds in the green tea that has demonstrated to have anticancer and antimitotic properties. The purpose of the present study was the evaluation of the effect of EGCG on the proliferation inhibition and apoptosis induction in a lymphoblastic leukemia cell line. Methods: Jurkat cell line was cultured in standard condition and in different concentrations of EGCG (0-100 micromolar) for 24, 48 and 72 hours. Cell viability was measured by MTS assay. Apoptosis induction was assessed by annexin V-FITC and flow cytometry analysis. Results: The MTS assay revealed that EGCG has decreased cell viability with a time and dose dependent manner. The level of cell apoptosis in all used concentrations of EGCG (50, 70 and 100 μm) was higher than control group (71%, 40% and 31% respectively vs. 8%) and reached to significant level at 100 μm concentration. Conclusion: The study indicated that EGCG is effective on proliferation inhibition and apoptotic induction in Jurkat lymphoblastic cell line. Therefore, the study of the mechanism of apoptosis induction could be a step of progress toward target therapy which might be considered in the future studies

Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019

Summary Background Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. Methods We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2·5th and 97·5th percentiles across 1000 posterior draws for each quantity of interest. Findings From an estimated 13·7 million (95% UI 10·9–17·1) infection-related deaths in 2019, there were 7·7 million deaths (5·7–10·2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13·6% (10·2–18·1) of all global deaths and 56·2% (52·1–60·1) of all sepsis-related deaths in 2019. Five leading pathogens—Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa—were responsible for 54·9% (52·9–56·9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185–285) per 100 000 population, and lowest in the high-income super-region, with 52·2 deaths (37·4–71·5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. Interpretation The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development