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Research Article
*Corresponding Author: Shalini Gupta Professor Department of Oral Pathology & Microbiology King George's Medical University, Lucknow, Uttar Pradesh, India, and Somali Sanyal, Assistant Professor Amity Institute of Biotechnology Amity University Uttar Pradesh, Lucknow, 226028, I
Citation: Kumud Nigam, Om Prakash Gupta, Somali Sanyal, Shalini Gupta, Saurabh Pratap Singh (2023), Metabolic Gene Polymorphisms and Antioxidant Influence Risk of Pre Oral Cancer and Oral Cancer, J. Cancer Research and Cellular Therapeutics, 7(1); DOI:10.31579/2640-1053/129
Copyright: © 2023 Chhabra S, this is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 30 August 2022 | Accepted: 25 December 2022 | Published: 02 January 2023
Keywords: oral cancer; pre oral cancer; genetic polymorphism; pcr; gstt1; gstm1
Many polymorphic genes that code enzymes involved in carcinogen biotransformation have been reported to be associated with development of cancer. GSTT1, GSTM1 genes that code phase II enzyme belongs to the glutathione S-transferases (GSTs) family and seems relevant for the susceptibility to oral diseases as it detoxify carcinogenic tobacco smoke to its excretal form. The aim of our study was to determine the association of GSTT1, GSTM1non null/null polymorphisms with the plasma level of GR, GSH and GST and susceptibility in pre oral cancer and oral cancer in North Indian population. The study group consisted of 230 patients of precancerous oral lesions (Leukoplakia 70, Oral Sub mucous fibrosis 90, Lichen Planus 70), 72 oral cancer and 300 cancer free healthy controls subjects. Genotyping was done by multiplex PCR method and antioxidant/antioxidant enzymes like reduced glutathione (GSH), glutathione reductase (GR) and glutathione S-transferase (GST) were estimated in blood plasma. Genotype frequency was calculated by Chi-square test. GST, GR and GSH activity were estimated spectrophotometrically. Null genotype of GSTT1 and GSTM1 polymorphisms increased the risk of oral diseases (OR=6.00, OR=2.62).The null genotype of GSTM1 polymorphism also increased the risk of OSMF & leukoplakia (OR=3.85, OR=3.82). Smokers, tobacco chewers and individual with more than one oral habit with null genotype of GSTT1 were at increased risk of pre oral cancer lesions (OR=12.15, OR=4.10, OR=23.95).
Oral cancer is the eighth most common cancer in the world and it causesmore than4,260,000 cases per annum among which ~128,000 passes annually (Hussain 2016). In India, frequency of oral cancer is 12.8 per 100,000 in males and 7.5 per 100,000 in females (Parul 2018). The frequency is high in rural areas in comparison to urban (Reddy 2004). It is complex disease related to genetic as well as environmental factors (Nigam 2016). Main etiological factors of oral cancer are smoking and alcohol consumptions while chewing tobacco or consumption of smokeless tobacco is particularly the main causalkey of oral cancer among Indian population (IARC 2012). In many patients occurrence of oral cancer is preluded with the development of precancerous oral lesions (Napier 2008; Rajaraman 2015). Pre oral cancer like lichen planus, leukoplakia and oral sub-mucous fibrosis have capacity to get converted into malignancy under the influence of several environmental factors/carcinogens [Rajaraman 2015; Radoi 2013; Guha 2013). However, genetic polymorphisms which may alter the metabolization of carcinogens (Hiyama 2008; Liao 2014)may influence the risk of having oral precancerous lesions and oral cancer (Scully 2000).
GSTT1 (Glutathione S-Transferase Theta 1) gene is present on chromosome number 22q11 and synthesize a phase II metabolic enzyme. Active metabolites of tobacco carcinogens get detoxified by this Phase II enzyme (Saikrishna 2013). Polymorphism in GSTT1 gene results in complete deletion of GSTT1 gene results in absence of its enzymatic activity and is known as null genotype. The null genotype has a low capacity to detoxify hence leads to the formation of DNA adducts and DNA damage which may eventually promote carcinogenesis. In Caucasians and Asians, Null genotype of GSTT1has been found to influence the risk of breast(Kimi 2016), lung (Sharma 2015), prostate (Wang 2016) and bladder cancer (Yu 2017).
GSTM1 (Glutathione S -Transferase Mu 1) is a protein coding gene presented on chromosome number 1p13. It is highly polymorphic in nature. It codes for the mu class of enzymes which conjugates glutathione to electrophilic compound such as therapeutic drugs, carcinogens, environmental toxins and oxidative stress products and help in their detoxification. Null mutations of GSTM1 have been linked with an increased risk of several cancers as it is associated with compromised detoxification of carcinogens and environmental toxins. Null genotype of GSTM1has been reported to be involved in the development of breast cancer (Kimi 2016) and lung cancer (Sharma 2015).
The risk of cancer is also enhanced by free radicals which are controlled naturally by antioxidant. GSH is the important intracellular antioxidant which protects organisms against oxidative stress and toxicity caused by deleterious hydrogen peroxide (Beevi 2004; Kumar 2012). It also plays major role against oral cancer by detoxifying the carcinogens and protecting lipid peroxidation by maintaining immune functions, regulating lymphocytic and mitogenic responses (Richie 2008). (GST) Glutathione S-transferase is a family of intracellular protein which detoxifies activated carcinogen metabolites by catalysis of their reaction with GSH(Coles 2001). Glutathione reeducates (GR) is another enzyme which is involved in the metabolism of xenobiotics and formation of the correct disulfide bonds of numerous protein.
The present study is aimed to determine the role of GSTM1, GSTT1 polymorphisms with the development of oral cancer and pre oral cancer. Along with the association of these polymorphisms with the plasma level of GR, GSH and GST levels was also explored.
Study Subjects
This study was evaluated on 602 subjects including 302 patients with previously treated and pathologically confirmed oral pre cancer and cancer who were registered at department of Oral Pathology & Microbiology, King George’s Medical University and 300 healthy controls. Institutional Ethics Committee of the King George’s Medical University, Lucknowhas been approved this study. An informed written consent was obtained from all subjects. Venous blood samples were collected in EDTA tubes and stored at −80 °C, till DNA extraction. DNA was extracted from blood samples by salting out method (Suguna 2014). Plasma was separated from the blood by centrifugation and was used for biochemical estimation.
Genotyping by PCR
Genotyping for GSTT1, GSTM1polymorphisms were done by polymerase chain reaction (PCR) method. PCR products were generated by using 10 ng of genomic DNA in 10 ul volume reactions containing 20 mMTris--HCl, 50 mMKCl, 2.0 mM MgCl2, 0.11 mM each dNTP, 0.3 mM each primer and 0.3 U Platinum Taq DNA polymerase (Invitrogen, Paisley, UK). The PCR products were stained with ethdium bromide and visualize on a 2% agarose gel. The genotype results were regularly checked and compared with known genotypes as controls using direct DNA sequencing of the amplified fragments (Figure 1,2).
Biochemical Assay
Reduced Glutathione (GSH ) assay.
The concentration of reduced glutathione was estimated in blood plasma. 100μL plasma was taken and the plasma proteins were precipitated with the addition of equal volume of 5% trichloroacetic acid (TCA). 0.1 mlof supernatant was taken and to this 0.9mL of 0.2M phosphate buffer (pH 7.5) was added to make the volume 1ml. To this 2ml of freshly prepared DTNB was added and incubated for 15 mins. The intensity of yellow color formed was spectrophotometrically read at 412nm against blank. GSH concentration was calculated by using the molar extinction coefficient of DTNB (14150M-1cm-1)(Moron 1979)’.
Glutathione reductase (GR) assay.
GR activity in the plasma samples was measured by preparing a 3 ml assay mixture containing 0.2mmol/L freshly prepared nicotinamide adenine dinucleotide phosphate (NaDPH), 0.5mmol/Loxidized glutathione (GSSG), 0.1mol/L phosphate buffer and 0.1ml of plasma sample. Decrease in absorbance at 340nm was measured for 3 minutes.GR activity was calculated using the molar extinction coefficient of NADPH (=6.2Mm-1cm-1). One unit of GR is defined as the amount of enzyme required to catalyze the reduction of 1 μmol/L of GSSG per minute at pH 7.5. One molecule of NADPH is oxidized per molecule of GSSG reduced. Therefore, the oxidation of NADPH (measured by loss of A340 nm) directly correlates with GSSG reduction (Sheokand 2008).
Glutathione S-transferase (GST) assay.
Plasma GST activity in the study subjects were estimated spectrophotometrically with reduced glutathione (GSH) and 1-chloro-2, 4-dinitrobenzene (CDNB) as substrates. The assay mixture consisted one ml of assay cocktail containing 980μlPBS pH 6.5, 10μl of 100 mM CDNB and 10 µl of 100 mM GSH.An increase in absorbance was measuredat 340nm for 3 minute. GST activity was calculated using extinction coefficient of 9.6nm-1 cm-1 and was expressed as n molar of CDNB conjugation/min (ref protocol). One unit of GST activity is the amount of enzyme which produces 1 µmol of GS-DNB conjugate/min under the conditions of the assay (Seyyedi 2005).
The distributions of genotype were checked for the Hardy–Weinberg equilibrium (HWE). Comparison between case and control were assessed by the chi‐square test with 1 degree of freedom. Odds ratio (OR) was calculated to measure the odds of having diseases with the relative frequency of different genotypes of the cases and controls. Odds ratio and p values were calculated by the software Epi-Info programme (http://wwwn.cdc.gov/epiinfo/). Biochemical values were expressed as the mean ± standard deviation (SD). Biochemical data obtained were subjected to statistical analysis using SPSS version 17 software.Student’s t test was used to compare the data among the groups and the differences were considered statistically significant if p values were 0.05 or less.
Demographics of the study population
The demographic profile including age, sex, habitual risk factor, tumor staging and environmental risk factors which may contribute to the development of oral cancer and pre oral cancer disease, are shown in Table 1. This study involved 302 oral cancer patients, including 203 (67%) male and 99 (33%) female. Calculated mean age of subject was 46.67. The mean age of controls [219(73%) males and 81(27%) females] was 38.02. Tobacco, smoking chewing and alcohol consumption have been observed to be significantly associated with the development of oral diseases (p value <0>
*=significant value
Table 1: Demographic parameters of patients and controls and their association with risk of Oral pre cancer & cancer
Individual & Combined genotypes of GSTT1 and GSTM1 polymorphisms and the risk of oral diseases
The frequency distribution of different genotypes of GSTT1 and GSTM1 polymorphisms among the cases of oral disease and control are presented in Table 2. GSTT1 and GSTM1 null genotypes showed significant association with the risk of oral cancer and oral pre cancer (p= 0.0001and 0.0001, respectively). Our combined genotype analysis showed that individuals who lacks both the GSTT1 and GSTM1 genes (null/null genotype) were at 7 times higher risk for the development of oral disease compared to individual who possess both the genes (non-null/non null genotype) (p= 0.0001,OR=7.27; 95% CI 3.26-16.25).
* significant association
Table 2: Distribution of different genotypes GSTT1, GSTM1polymorphisms among cases of oral diseases (pre cancer and cancer) and healthy controls
Genotypes of GSTT1 and GSTM1 polymorphisms and risk of different pre oral cancer and oral cancer
The frequency of different genotypes of GSTT1, GSTM1 polymorphisms among patients of different pre oral cancer diseases, oral cancer and healthy control subjects are showed in Table 3.Compared to the non-null genotypes of GSTM1, GSTT1 polymorphisms the risk of developing OSMF was significantly higher with null genotypes (OR=14.82; 95%CI 8.39-26.19 and OR=3.85; 95% CI 2.20-6.72, respectively)and are listed in Table 3.Null genotype of GSTT1 polymorphism was significantly increased the risk for the development of lichen planus, leukoplakia, and malignancy (p value=0.0009, OR=3.11, 95% CI=1.61-6.00; p value=0.0001, OR=7.15, 95%CI=3.91-13.08; p value=0.01, OR=2.45, 95% CI=1.23-4.86).Individual who possess the GSTT1 gene but lacks GSTM1 gene (i.e having GSTT1 non-null/GSTM1null genotype) were at increased risk of OSMF and leukoplakia (OR=6.82, and 5.40 respectively). Similarly risk of OSMF, Lichen planus and leukoplakia were higher among the subjects lacking the GSST1 gene but possess the GSTM1 gene (i.esubjects with GSTT1 null/GSTM1non null genotype)(OR= 23.25, 4.12 and 10.08 respectively). With reference to non-null/ non-null genotypes for GSTT1 and GSTM1 genes risk of developing OSMF and Leukoplakia lesion were significantly higher with the null/null genotype (OR= 25.47and 4.34 respectively).
| Genotypes | OSMF n (%) |
p- value&OR (95% CI) | LichenPlanus n (%) |
p- value&OR (95% CI) | Leukoplakia n (%)
|
p- value&OR (95% CI) |
Malignancy
n (%) |
p- value&OR (95% CI) | Control n (%) |
| GSTT1 Genotypes | |||||||||
| Non-null | 34 (38) | Ref | 52 (75) | Ref | 39 (56) | Ref | 55 (79) | Ref | 270 (90) |
| Null | 56 (62) | 0.0001* 14.82 (8.39-26.19) | 18 (25) | 0.0009* 3.11 (1.61-6.00) | 31 (44) | 0.0001* 7.15 (3.91-13.08) | 15 (21) | 0.01* 2.45 (1.23-4.86) | 30 (10) |
| GSTM1 Genotypes | |||||||||
| Genotypes | OSMF n (%) |
p-value&OR (95% CI) | Lichen Planus n (%) |
p-value&OR (95% CI) | Leukoplakia n (%) |
p-value&OR (95% CI) |
Malignancy n(%) |
p-valueOR & (95% CI) |
Controls n (%) |
| Non-null | 59 (66) | Ref | 55 (78) | Ref | 46 (66) | Ref | 61 (87) | Ref |
264 (88) |
| Null | 31 (34) | 0.0001* 3.85 (2.20-6.72) | 15 (22) | 0.06 2.00 (1.02-3.90) | 24 (34) | 0.0001* 3.82 (2.09-7.00) | 09 (13) | 0.84 1.08 (0.49-2.36) |
36 (12) |
Combined Genotype
| |||||||||
Non-null/ Non-null | 19 (21) | Ref | 40 (57) | Ref | 24 (34) | Ref | 50 (71) | Ref | 242 (81) |
| Non-null/Null | 15 (17) | 0.0001* 6.82 (3.12-14.91) | 12 (17) | 0.02 2.59 (1.21-5.51) | 15 (21) | 0.0001* 5.40 (2.54-11.48) | 05 (07) | 0.96 0.86 (0.31-2.34) | 28 (09) |
| Null/Non-null | 40 (44) | 0.0001* 23.15 (11.50-46.59) | 15 (21) | 0.0002* 4.12 (1.97-8.61) | 22 (32) | 0.0001* 10.08 (4.88-2.08) | 11 (16) | 0.04 2.42 (1.10-5.30) | 22 (07) |
| Null/Null | 16 (18) | 0.0001* 25.47 (9.66-67.12) | 03 (05) | 0.44 2.26 (0.57-8.91) | 09 (13) | 0.0001* 4.34 (4.00-32.12) | 04 (06) | 0.29 2.42 (0.70-8.35) | 08 (03) |
*= significant value
Table 3: Distribution of different genotypes GSTT1,GSTM1 polymorphisms among the subjects of oralsubmucous fibrosis, Lichenplanus, Leukoplakia, oral cancer & controls
GSTT1, GSTM1 gene polymorphisms in relation to different habit of patients with oral cancer and pre oral cancer
Distribution of different genotypes for GSTT1 and GSTM1 null/non-null polymorphisms among the tobacco chewers, alcohol consumers and smokers are detailed in Table 4. The null genotype of GSTT1 was found to increase the risk for pre oral cancer and that was irrespective of individuals oral habits (Table 4). Whereas, the risk of oral cancer was increased by the GSTT1 Null genotype only in the individuals who had more than 1oral habit (OR=9.11).The null genotype of GSTM1 was found to increase the risk of pre oral cancer among the smokers and individuals with more than 1 oral habits (OR=26.75 and 7.22 respectively). No interaction of GSTM1 genotype with the oral habits were observed in risk modulation of oral cancer.
Genotypes
|
Pre-oral cancer n (%) |
p-value |
Odd ratio (95% CI) |
Oral cancer n (%)
|
p- value |
Odd ratio (95% CI) | Controls n (%) |
| GSTT1 Genotypes | |||||||
| No Habit | |||||||
| Non-null | 39 (17) | Ref | 1 | 1 (01) | Ref | 1 | 165 (55) |
| Null | 40 (17) | 0.0001* | 8.90 (4.65-17.03) | 1 (01) | 0.51 | 8.68 (0.52-144.66) | 19 (07) |
| Smokers | |||||||
| Non-null | 38 (16) | Ref | 1 | 1 (01) | Ref | 1 | 44 (15) |
| Null | 21 (09) | 0.0003* | 12.15 (2.67-55.27) | 00 | - | - | 2 (0.7) |
| Tobacco | |||||||
| Non-null | 21 (09) | Ref | 1 | 19 (28) | Ref | 1 | 30 (10) |
| Null | 23 (10) | 0.007* | 4.10 (1.54-10.93) | 3 (04) | 0.71 | 0.59 (0.13-2.51) | 8 (02) |
| Alcohol | |||||||
| Non-null | 5 (02) | Ref | 1 | 00 | Ref | 1 | 00 |
| Null | 4 (02) | - | - | 1 (01) | - | - | 00 |
| >1 Habit | |||||||
| Non-null | 22 (10) | Ref | 1 | 34 (49) | Ref | 1 | 31 (10) |
| Null | 17 (08) | 0.0003* | 23.95 (2.96-193.67) | 10 (15) | 0.03* | 9.11 (1.10-75.43) | 1 (0.3) |
| GSTM1 Genotypes | |||||||
| No Habit | |||||||
| Non-null | 60 (26) | Ref | 1 | 2 (03) | Ref | 1 | 157 (52) |
| Null | 19 (08) | 0.09 | 1.84 (0.95-3.55) | 1 (02) | 0.93 | 2.90 (0.25-33.20) | 27 (9) |
| Smokers | |||||||
| Non-null | 37 (16) | Ref | 1 | 1 (02) | Ref | 1 | 45 (15) |
| Null | 22 (10) | 0.0001* | 26.75 (3.44-208.09) | 00 | - | - | 1 (01) |
| Tobacco | |||||||
| Non-null | 32 (14) | Ref | 1 | 20 (28) | Ref | 1 | 32 (10) |
| Null | 12 (05) | 0.32 | 2.00 (0.66-5.98) | 01 (1) | 0.40 | 0.26 (0.02-2.38) | 06 (02) |
| Alcohol | |||||||
| Non-null | 04 (02) | Ref | 1 | 01 (01) | Ref | 1 | 00 |
| Null | 04 (02) | - | - | 00 | - | - | 00 |
| >1 Habit | |||||||
| Non-null | 27 (12) | Ref | 1 | 37 (53) | Ref | 1 | 30 (10) |
| Null | 13 (05) | 0.01* | 7.22 (1.49-34.96) | 07 (10) | 0.35 | 2.83 (0.54-14.68) | 02 (01) |
*significant association
Table 4: Habitual riskof different genotypes GSTT1, GSTM1polymorphisms among oral pre cancer (Oral submucous fibrosis + Lichenplanus, +Leukoplakia), cancer and controls
Interaction between GSH, GR, GST with GSTT1, GSTM1 gene polymorphisms
The activity of GST and GR and plasma level of GSH were estimated and correlated with different genotypes of GSTT1 and GSTM1 polymorphisms. The plasma level GSH and the activity of GST and GR was similar between the different genotypes of GSTT1 and GSTM1 non null/null polymorphism (Table 5).
GSTT1 and GSTM1 are Phase II metabolism pathway genes and are involved in detoxification of tobacco carcinogens by conjugation reaction. GSTM1 and GSTT1 absent/null genotype would low the capacity of the detoxification process. Thus, polymorphisms of GSTT1, GSTM1 genes may affect the susceptibility of different cancers.
In this study we observed that absent genotype of GSTT1 & GSTM1 polymorphisms increased the risk of oral diseases. Null genotype of GSTT1 polymorphism increased the risk of all kind of pre oral cancer & oral cancer and the null genotype of GSTM1 polymorphism increased the risk of OSMF and leukoplakia. Compared to presence of both the genes, absence of any one of them significantly increased the risk for oral diseases. The GSTT1 deletion genotype has been suggested by others to be associated with the risk of different cancers, including lung cancer in Asians (Raimondi 2006), gastric cancer (Saadat 2006), leukemia (Ye 2005), and hepatocellular carcinoma (White 2008). Polymorphisms in a GSTT1 and GSTM1 null genotype suggested to confer an increased risk for oral cancer by Sreelekha et al. (2008).
Genetic polymorphisms in GSTT1, GSTM1 and tobacco use to play key roles in development of different cancers (Choudhury 2014; 32. Talukdar 2013). In the present study genotypes of GSTT1 and GSTM1 were also found to interact with individuals oral habits like tobacco smoking and chewing in modulating the risk of both pre oral cancer and oral cancer. Similarly, absence of GSTM1 and GSTT1 genes showed to influence the risk of HNSCC risk among tobacco and alcohol consumers in the German population (Gronau 2003).
Antioxidants can reduce oxidative damage and inflammation, delay cancer progression, and prevent cancer recurrence by scavenging free radicals (Sarangarajan 2017). Different studies have successfully used vitamins or phytochemicals as anti-oxidative adjuvants for head and neck squamous cell carcinoma (Eastham 2018; Jain 2017). Anti-oxidative nutrients, which can also be obtained from a healthy diet that includes plenty of fresh vegetables and fruits, have been proposed to reduce the risk of head and neck cancer (Chang 2017). The use of tobacco may have suppressed the production of antioxidant enzymes, which was evident in pre oral and OSCC patients, who were tobacco users. The GSH/GSSG redox couple is commonly used in measuring oxidative stress inside the body. Previous studies have reported a strong correlation between decreased risks of oral cancer with increasing blood glutathione levels
(Richie 2008). In one Indian study Plasma glutathione level is consistently reduced in the advanced stages of oral cancer when compared to initial stages (Manoharam 2005). In glutathione redox cycle, GR, NAD(P)H-dependent enzymatic antioxidant, is the important enzyme and it efficiently maintains the reduced pool of GSH. Many studies reported that GRactivity getdecreased in oral cancer in response to oxidative stress (Fiaschi 2005). GSTT1 protein catalyses the conjugation of reduced glutathione to several electrophilic and hydrophobic compounds. Similarly GSTM1 synthesize a mu class of enzymes which conjugates reduced glutathione to electrophilic compound such as therapeutic drugs, carcinogens, environmental toxins and oxidative stress products and help in their detoxification. There fore presence or absence of these two enzyme may influence the risk of cancer by regulating the glutathione redox cycle. However, in our study we found plasma level GSH and the activity of GST and GR was similar between the different genotypes of GSTT1 and GSTM1 non null/null polymorphism in oral disease.
The genetic polymorphism in GSTT1 and GSTM1 can be used as biomarkers of susceptibility for developing oral disease. However, we did not observe any correlation between the oxidative stress in patients and genotypes of GSTT1, GSTM1 polymorphism which may be due to small sample size or estimation of a few parameters and therefore, the findings only provide an index. Further studies are required to be conducted with large sample size to confirm the role of GSTT1, GSTM1 polymorphisms and oxidative stress in pre oral cancer and oral cancer patients before using these polymorphisms as susceptibility biomarker
The project was funded through Indian Council for Medical Research (ICMR) India and Uttar Pradesh Council of Science and Technology
The work is supported by Indian Council for Medical Research (ICMR) and Uttar Pradesh Council of Science and Technology (UPCST).
Ethics approval: Approval was taken from Institutional Ethical Committee of King George’s Medical University, Lucknow, Uttar Pradesh, India
Author commitments: The manuscript is submitted with the full knowledge and consent of all co-authors and all co- authors will be informed of all correspondence about the manuscript.
Data Deposition statement: All the data and material is included in the manuscript.
Conflicts of interest/Competing interests: Authors declare “no conflict” of interest.
Author contributions:
Kumud Nigam : writing original draft
Om prakash gupta: Analysis, Final editing & correction
Somali Sanyal: Visualisation, Resources, supervision
Shalini Gupta: Conceptualisation & study design
Saurabh Pratap Singh: Investigation and review
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"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
