JSM Enzymology and Protein Science

Beneficial Effect of Homocysteine Lowering on Lectin-Like Oxidized Low- Density Lipoprotein Receptor-1 Level in Hyperhomocysteinemic Mice

Short Communication | Open Access | Volume 2 | Issue 1

  • 1. Université Paris Diderot, Sorbonne Paris Cité, Biologie Fonctionnelle et Adaptative (BFA), France
  • 2. Department of Translational Research, Institut Curie, France
  • 3. Center for Molecular and Vascular Biology, University of Leuven, Belgium
+ Show More - Show Less
Corresponding Authors
N Janel, Université Paris Diderot, Sorbonne Paris Cité, Biologie Fonctionnelle et Adaptative (BFA), 75205 Paris cedex 13, France, Tel: 00-331-5727-8360; Fax: 00-331-5727-8354

Tlili A, de Koning L, Dubois T, De Geest B, Janel N (2016) Beneficial Effect of Homocysteine Lowering on Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Level in Hyperhomocysteinemic Mice. JSM Enzymol Protein Sci 1(1): 1008.


CBS: Cystathionine Beta Synthase; DYRK1A: Dual-Specificity Tyrosine-Phosphorylation-Regulated Kinase 1A; GSK3 : Glycogen Synthase Kinase 3; Hhcy: Hyperhomocysteinemia; Hcy: Homocysteine; LOX-1: Lectin-like Oxidized Low-Density Lipoprotein Receptor-1; Oxldl: Oxidized Low Density Lipoprotein Particles; PON-1: Paraoxonase-1


Since its discovery and toxicity in human disease, the metabolism of homocysteine (hcy) and its genetic defects have been extensively explored [1]. The main therapeutic approach to treating Hcy defects is supplementation with B vitamins, in combination with protein restriction, and cysteine supplementation [2-4]. Although treatments can be effective, some patients with hyperhomocysteinemia (Hhcy) are unresponsive to conventional treatment with B vitamins [5]. Therefore, new therapeutic approaches have been sought in recent years to reduce the plasma level of this amino acid, which is considered to be an independent risk factor for the progression of vascular disease [6]. We have recently focus on two major new therapeutic approaches, the first being a preventive approach through diet by supplementation with polyphenols, and the other a reinforcement of Hcy metabolism by genetic manipulation. Both approaches have been designed to improve the health of vessels in patients by targeting the principal organ of Hcy metabolism, the liver. Indeed, impairment of hepatic Hcy metabolism can lead to higher intracellular concentrations and export to the blood. Hence, plasma Hcy level is an important reflection of hepatic methionine metabolism and of the rate of processes modified by B vitamins. We found, on the one way, that chronic supplementation of polyphenolic extract from red wine in Hhcy mice due to cystathionine beta synthase (CBS) deficiency and fed a high-methionine enriched diet decreased plasma Hcy level [7]. Similar results were observed with a diet that was supplemented with purified catechin [8,9] or epicatechin [9]. On the other way, our results implicated the dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), an enzyme that is thought to play a role in signaling pathways regulating proliferation and differenciation, in different aspects of Hcy metabolism, with its hepatic protein expression negatively correlated with plasma Hcy level [10-12]. DYRK1A has been therefore showed to be a good candidate for gene therapy to normalize Hcy levels. However, a large body of evidence also implicates DYRK1A in altering synaptic plasticity and facilitating neurodegeneration and dementia [13]. Thus, therapy must be targeted rather than broad. We therefore implemented targeted gene therapy to overexpress DYRK1A specifically in liver [14,15]. For this, a specific adenoviral vector was used to rescue Dyrk1a expression in the liver of Hhcy mice, and plasma Hcy levels significantly decreased after hepatocyte-specific Dyrk1a gene transfer in Hhcy mice [14,15].

One of the key xenobiotic metabolizing enzymes (XME) affected by Hcy is Paraoxonase-1 (PON-1). PON-1 is a phase I XME associated with serum high density lipoprotein (HDL), and is synthesized in the liver [16]. Hhcy mice exhibit a decrease of liver and plasma PON-1 activity, with a strong correlation with plasma Hcy level [17-19]. Supplementation with polyphenolic extract or purified catechin in Hhcy mice induces increased activity of PON-1 in liver and in plasma [7-9]. Targeted hepatic rescue of expression of Dyrk1a also resulted in elevated activity of plasma PON-1 [14,15], which plays a major role in the protective function of HDL against endothelial dysfunction. People with Hhcy exhibit increased expression of lectin-like oxidized lowdensity lipoprotein receptor-1 (LOX-1) in mononuclear cells of peripheral blood [20]. LOX-1 activation allows oxidized low density lipoprotein particles (OxLDL) to penetrate macrophages and induce their transformation into foam cells, playing a vital role in regulating the progression of atherosclerotic lesions. Hhcy mice exhibit increased aortic expression and serum amount of LOX-1 [7,9]. Supplementation with polyphenolic extract, catechin or epicatechin, induces a decrease of LOX-1 in aorta and plasma of Hhcy mice [7,9]. It has been demonstrated that LOX-1 activation causes endothelial apoptosis and inflammation, and polyphenol supplementation has beneficial effects on biochemical markers of endothelial dysfunction due to Hhcy [7,9,21]. Commensurate with the effect on PON-1 activity in plasma of Hhcy mice, targeted hepatic Dyrk1a gene transfer can abolish the negative effect of Hhcy on signaling pathways implicated when compromised in impaired endothelial function [14]. Therefore, we aimed to extend our previous findings by analyzing the effect of hepatocyte-specific Dyrk1a gene transfer on plasma LOX-1 level in HHcy mice.


Experimental animals

All procedures were carried out in accordance with the ethical standards of French and European regulations (European Communities Council Directive, 86/609/EEC). Official authorization from the French Ministry of Agriculture was granted to perform research and experiments on animals (authorization number 75-369), and the experimental protocol was approved by the institutional animal care and use committee of the Paris Diderot University (CEEA40). Mice were housed in a controlled environment with unlimited access to food and water on 12-h light/dark cycle. Number of mice and suffering were minimized as possible. Mice heterozygous for targeted disruption of the Cbs gene (Cbs +/-) were generously donated by Dr. N. Maeda (Department of Pathology, University of North Carolina, Chapel Hill, NC, USA) [22]. Cbs +/- mice, on a C57BL/6 background, were obtained by mating male Cbs +/- mice with female wild-type C57BL/6 (Cbs +/+) mice. The E1E3E4-deleted adenoviral vector “AdDYRK1A” was constructed to induce hepatocyte specific overexpression of DYRK1A, and injected by the retro-orbital sinus to have 2 x 1012 adenoviral particles/kg body weight as described previously [14].

Preparation of serum samples, tissue collection, and ELISA assay

When mice were euthanized, blood samples were collected into tubes containing a 1/10 volume of 3.8% sodium citrate and placed on ice immediately. Plasma was isolated by centrifugation at 2,500 x g for 15 min at 4° C. Aorta were harvested, snapfrozen, and stored at -80° C until use. Levels of plasma LOX-1 were determined using an ELISA from R&D Systems, Inc. (R&D Systems Europe, Lille, France).

Protein extraction and reverse phase protein array analysis

Protein extraction from liver and aorta and quantification by slot blotting and reverse phase protein array analysis (RPPA) were performed as described [14].

Data analysis 

Statistical analysis was done with one-way analysis of variance (ANOVA) followed by Fisher post-hoc test using Statview software. The results are expressed as medians with interquartile ranges. Data were considered significant when p <0.05.


Effect on Hcy lowering on plasma LOX-1 levels

We previously found an increased plasma level of soluble LOX1 in Cbs +/- mice fed a high-methionine diet [7,9]. We confirmed this increase in plasma of Cbs +/- mice compared to wild type Cbs +/+ mice (Figure 1). Conversely, hepatic DYRK1A protein level was decreased in Cbs +/- mice compared to wild type Cbs +/+ mice (64.7 ± 5.9 vs 111 ± 7.5; p <0.0005; n=8 mice for each group) as previously described [11]. Injection of AdDYRK1A resulted in a significant decrease in plasma LOX-1 level (Figure 1).

Figure 1 Effect of hepatocyte-specific Dyrk1a gene transfer (AdDYRK1A) on  plasma LOX-1 level. n = 8 mice for each group

Figure 1: Effect of hepatocyte-specific Dyrk1a gene transfer (AdDYRK1A) on plasma LOX-1 level. n = 8 mice for each group

Conversely, hepatic DYRK1A protein level was increased in Cbs +/- mice injected with AdDYRK1A compared to Cbs +/- mice (389 ± 78 vs 64.7 ± 5.9 p <0.0001; n=8 mice for each group) as previously described [14]. Therefore, in relation to our previous work which underlines the effect of supplementation with polyphenols and of hepatocyte-specific Dyrk1a gene transfer on plasma Hcy level [7,8,9,14,15], the decrease in plasma Hcy shows a beneficial effect on plasma LOX-1 level in HHcy mice. Polyphenols can act at several locations to counteract the cytotoxicity of Hcy, thereby preventing vascular pathology related to liver phenotypes. A healthy liver supports vascular health. The down-regulation of LOX-1 may be a potential treatment to protect against ox-LDLinduced endothelial cell injury in high-risk vascular diseases. Ox-LDL-induced endothelial cell apoptosis can be reduced by inhibiting LOX-1 expression and by increasing the activation of PI3k/Akt signaling pathways [23]. The PI3K/Akt pathway is a pivotal signal pathway involved in cell survival and metabolism [24]. PI3K/Akt has been shown to affect several important endothelial functions to promote endothelial cells survival [25]. We previously found a decrease of phospho-Akt in aorta of HHcy mice, which is restored by hepatocyte-specific Dyrk1a gene transfer [14].

Figure 2 Effect of hepatocyte-specific Dyrk1a gene transfer (AdDYRK1A) on  aortic phospho-mTOR and cyclin D1 levels. (A) – Phosphorylation of mTOR  determined by RPPA. Relative protein level was determined by normalization  from PmTOR with that of total mTOR. (B) – cyclin D1 protein level determined  by RPPA. Data were normalized to the mean of wild-type mice (Cbs+/+). n = 8  mice for each group

Figure 2: Effect of hepatocyte-specific Dyrk1a gene transfer (AdDYRK1A) on aortic phospho-mTOR and cyclin D1 levels. (A) – Phosphorylation of mTOR determined by RPPA. Relative protein level was determined by normalization from PmTOR with that of total mTOR. (B) – cyclin D1 protein level determined by RPPA. Data were normalized to the mean of wild-type mice (Cbs+/+). n = 8 mice for each group

Effect on Hcy lowering on Pi3K/Akt/mTor pathway in aorta

Given the fact that PI3K/Akt/mTOR pathway plays a key role in cellular homeostasis through its role in regulation of apoptosis, cell growth, cell cycle and angiogenesis, we also analysed mTOR phosphorylation. We found a decreased phosphorylation of mTOR in aorta of Cbs +/- mice (Figure 2A), and injection of AdDYRK1A resulted in a significant increase (Figure 2A). Previous results demonstrated the role of Pi3K for upregulation of cyclin D1 [26]. Akt also promotes cyclin D1 translation via indirect activation of mTOR [27], and prevents phosphorylation and degradation of cyclin D1 by phosphorylation and inactivation of glycogen synthase kinase 3 (GSK3) at Ser9 [28]. Hepatocytespecific Dyrk1a gene transfer not only resulted in PI3K/Akt activation but also in GSK3 inhibition in aorta of Hhcy mice [14]. We therefore analysed the protein level of cyclin D1, and found a decrease in aorta of Cbs +/- mice (Figure 2B), which is abolished after injection of AdDYRK1A to Cbs +/- mice (Figure 2B). Previous results demonstrated the ability of Hcy to decrease mRNA expression of cyclin D1 in human umbilical vein endothelial cells [29]. Further, hepatocyte-specific Dyrk1a gene transfer rescues Akt/GSK3/cyclin D1 signaling pathways not only in aorta but also in liver of HHcy mice [15]. Taken together, Hcy lowering by AdDYRK1A injection abolishes the negative effect on PI3K/Akt/ mTOR pathway and on cyclin D1 protein level. CONCLUSION In conclusion, taken together with our previous works, we found that two different approaches one preventive and based on chronic supplementation of polyphenols, and the other genetic and based on restoring hepatic function make it possible to normalize plasma Hcy level and its associated endothelial dysfunction by restoring LOX-1 level in Hhcy mice.


We thank Dr. N. Maeda (Department of Pathology, University of North Carolina, Chapel Hill, NC) for providing heterozygous Cbs-null mice. We thank D. Quintas for technical assistance. We acknowledge the platform accommodation and animal testing of the animal house at the Institute Jacques-Monod (University Paris Diderot) and the FlexStation3 Facility of the Functional and Adaptative Biology (BFA) laboratory. This work was supported by the Association Gaspard Félix (L’AGAFE). Leanne de koning and the Institut Curie RPPA platform are supported by the Cancéropole Ile-de-France.


1. Schalinske KL, Smazal AL. Homocysteine imbalance: a pathological metabolic marker. Adv Nutr. 2012; 3: 755-762.

2. Wilcken DE, Wilcken B. The natural history of vascular disease in homocystinuria and the effects of treatment. J Inherit Metab Dis. 1997; 20: 295-300.

3. Yap S, Naughten ER, Wilcken B, Wilcken DE, Boers GH. Vascular complications of severe hyperhomocysteinemia in patients with homocystinuria due to cystathionine beta-synthase deficiency: effects of homocysteine-lowering therapy. Semin Thromb Hemost. 2000; 26: 335-340.

4. Yap S, Boers GH, Wilcken B, Wilcken DE, Brenton DP, Lee PJ, et al. Vascular outcome in patients with homocystinuria due to cystathionine beta-synthase deficiency treated chronically: a multicenter observational study. Arterioscler Thromb Vasc Biol. 2001; 21: 2080-2085.

5. Mudd SH, Skovby F, Levy HL, Pettigrew KD, Wilcken B, Pyeritz RE, et al. The natural history of homocystinuria due to cystathionine betasynthase deficiency. Am J Hum Genet. 1985; 37: 1-31. 

6. Heneghan HM, Sultan S. Homocysteine, the cholesterol of the 21st century. Impact of hyperhomocysteinemia on patency and amputation-free survival after intervention for critical limb ischemia. J Endovasc Ther. 2008; 15: 399-407.

7. Noll C, Hamelet J, Matulewicz E, Paul J-L, Delabar J-M, Janel N. Effects of red wine polyphenolic compounds on paraoxonase-1 and lectin-like oxidized low-density lipoprotein receptor-1 in hyperhomocysteinemic mice. J Nutr Biochem. 2009; 20: 586-596.

8. Hamelet J, Demuth K, Dairou J, Ledru A, Paul JL, Dupret JM, et al. Effects of catechin on homocysteine metabolism in hyperhomocysteinemic mice. Biochem Biophys Res Commun. 2007; 355: 221-227.

9. Noll C, Lameth J, Paul J-L, Janel N. Effect of catechin/epicatechin dietary intake on endothelial dysfunction biomarkers and proinflammatory cytokines in aorta of hyperhomocysteinemic mice. Eur J Nutr. 2013; 52: 1243-1250.

10. Noll C, Planque C, Ripoll C, Guedj F, Diez A, Ducros V, et al. DYRK1A, a novel determinant of the methionine-homocysteine cycle in different mouse models overexpressing this Down-syndrome-associated kinase. PLoS ONE. 2009; 4: 7540.

11. Hamelet J, Noll C, Ripoll C, Paul JL, Janel N, Delabar JM. Effect of hyperhomocysteinemia on the protein kinase DYRK1A in liver of mice. Biochem Biophys Res Commun. 2009; 378: 673-677.

12. Delabar JM, Latour A, Noll C, Renon M, Salameh S, Paul JL, et al. Onecarbon cycle alterations induced by Dyrk1a dosage. Mol Genet Metab Rep. 2014; 1: 487-492.

13. de la Torre R, de Sola S, Hernandez G, Farré M, Pujol J, Rodriguez J, et al. Safety and efficacy of cognitive training plus epigallocatechin-3- gallate in young adults with Down’s syndrome (TESDAD): a doubleblind, randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016; 15: 801-810.

14. Tlili A, Jacobs F, de Koning L, Mohamed S, Bui LC, Dairou J, et al. Hepatocyte-specific Dyrk1a gene transfer rescues plasma apolipoprotein A-I levels and aortic Akt/GSK3 pathways in hyperhomocysteinemic mice. Biochim Biophys Acta. 2013; 1832: 718- 728.

15. Latour A, Salameh S, Carbonne C, Daubigney F, Paul JL, Kergoat M, et al. Corrective effects of hepatotoxicity by hepatic Dyrk1a gene delivery in mice with intermediate hyperhomocysteinemia. Mol Genet Metab Reports. 2015; 2: 51-60.

16. Chambers JE. PON1 multitasks to protect health. Proc Natl Acad Sci U S A. 2008; 105: 12639-12640.

17. Robert K, Chassé JF, Santiard-Baron D, Vayssettes C, Chabli A, Aupetit J, et al. Altered gene expression in liver from a murine model of hyperhomocysteinemia. J Biol Chem. 2003; 278: 31504-31511.

18. Janel N, Robert K, Chabert C, Ledru A, Gouédard C, Barouki R, et al. Mouse liver paraoxonase-1 gene expression is downregulated in hyperhomocysteinemia. Thromb Haemost. 2004; 92: 221-222.

19. Hamelet J, Aït-Yahya-Graison E, Matulewicz E, Noll C, Badel-Chagnon A, Camproux AC, et al. Homocysteine threshold value based on cystathionine beta synthase and paraoxonase 1 activities in mice. Eur J Clin Invest. 2007; 37: 933-938.

20. Holven KB, Scholz H, Halvorsen B, Aukrust P, Ose L, Nenseter MS. Hyperhomocysteinemic subjects have enhanced expression of lectinlike oxidized LDL receptor-1 in mononuclear cells. J Nutr. 2003; 133: 3588-3591.

21. Hung CH, Chan SH, Chu PM, Tsai KL. Homocysteine facilitates LOX-1 activation and endothelial death through the PKCβ and SIRT1/HSF1 mechanism: relevance to human hyperhomocysteinaemia. Clin Sci (Lond). 2015; 129: 477-487.

22. Watanabe M, Osada J, Aratani Y, Kluckman K, Reddick R, Malinow MR, et al. Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia. Proc Natl Acad Sci U S A. 1995; 92: 1585-1589.

23. Qin M, Luo Y, Meng XB, Wang M, Wang HW, Song SY, et al. Myricitrin attenuates endothelial cell apoptosis to prevent atherosclerosis: An insight into PI3K/Akt activation and STAT3 signaling pathways. Vascul Pharmacol. 2015; 70: 23-34.

24. García-Cardeña G, Anderson KR, Mauri L, Gimbrone MA Jr. Distinct mechanical stimuli differentially regulate the PI3K/Akt survival pathway in endothelial cells. Ann N Y Acad Sci. 2000; 902: 294-297.

25. Tie G, Yan J, Yang Y, Park BD, Messina JA, Raffai RL, et al. Oxidized lowdensity lipoprotein induces apoptosis in endothelial progenitor cells by inactivating the phosphoinositide 3-kinase/Akt pathway. J Vasc Res. 2010; 47: 519-530.

26. Takuwa N, Fukui Y, Takuwa Y. Cyclin D1 expression mediated by phosphatidylinositol 3-kinase through mTOR-p70(S6K)-independent signaling in growth factor-stimulated NIH 3T3 fibroblasts. Mol Cell Biol. 1999; 19: 1346-1358.

27. Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev. 2004; 18: 1926-1945.

28. Alao JP. The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention. Mol Cancer. 2007; 6: 24.

29. Outinen PA, Sood SK, Pfeifer SI, Pamidi S, Podor TJ, Li J, et al. Homocysteine-induced endoplasmic reticulum stress and growth arrest leads to specific changes in gene expression in human vascular endothelial cells. Blood. 1999; 94: 959-967.


Background: Hyperhomocysteinemia often results from vitamin deficiency and/or an unhealthy lifestyle. Because the condition is a risk factor for developing cerebrovascular disease or atherosclerosis, approaches that decrease plasma homocysteine level are needed to alleviate this public health issue. Unfortunately, as the standard treatment of supplementation with B vitamins has shown limited benefit, novel therapies must be explored. We have recently focus on two novel approaches, the first being a preventive approach through diet by supplementation with polyphenols, and the other a reinforcement of homocysteine metabolism by targeting the principal organ of homocysteine metabolism, the liver. Chronic supplementation of polyphenols decreased plasma homocysteine and LOX-1 level in hyperhomocysteinemic mice. Plasma homocysteine level also significantly decreased after hepatocyte-specific DYRK1A gene transfer in hyperhomocysteinemic mice, DYK1A being an enzyme implicated in different aspects of homocysteine metabolism.
Aim: We aimed to extend our previous findings by analyzing the effect of hepatocyte-specific Dyrk1a gene transfer on plasma LOX-1 level in hyperhomocysteinemic mice. 
Materials and methods: Plasma LOX-1 level and some signalling pathways in aorta were assessed by ELISA and RPPA.
Results: Hepatocyte-specific DYRK1A gene transfer restored plasma LOX-1 level and Pi3K/Akt/mT or pathway in aorta of hyperhomocysteinemic mice.
Discussion: Hepatocyte-specific DYRK1A gene transfer makes it possible to normalize plasma homocysteine level and its associated endothelial dysfunction by restoring LOX-1 level in hyperhomocysteinemic mice as previously found with polyphenols supplementation.

Tlili A, de Koning L, Dubois T, De Geest B, Janel N (2016) Beneficial Effect of Homocysteine Lowering on Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Level in Hyperhomocysteinemic Mice. JSM Enzymol Protein Sci 1(1): 1008

Received : 15 Nov 2016
Accepted : 05 Dec 2016
Published : 07 Dec 2016
Annals of Otolaryngology and Rhinology
ISSN : 2379-948X
Launched : 2014
JSM Schizophrenia
Launched : 2016
Journal of Nausea
Launched : 2020
JSM Internal Medicine
Launched : 2016
JSM Hepatitis
Launched : 2016
JSM Oro Facial Surgeries
ISSN : 2578-3211
Launched : 2016
Journal of Human Nutrition and Food Science
ISSN : 2333-6706
Launched : 2013
JSM Regenerative Medicine and Bioengineering
ISSN : 2379-0490
Launched : 2013
JSM Spine
ISSN : 2578-3181
Launched : 2016
Archives of Palliative Care
ISSN : 2573-1165
Launched : 2016
JSM Nutritional Disorders
ISSN : 2578-3203
Launched : 2017
Annals of Neurodegenerative Disorders
ISSN : 2476-2032
Launched : 2016
Journal of Fever
ISSN : 2641-7782
Launched : 2017
JSM Bone Marrow Research
ISSN : 2578-3351
Launched : 2016
JSM Mathematics and Statistics
ISSN : 2578-3173
Launched : 2014
Journal of Autoimmunity and Research
ISSN : 2573-1173
Launched : 2014
JSM Arthritis
ISSN : 2475-9155
Launched : 2016
JSM Head and Neck Cancer-Cases and Reviews
ISSN : 2573-1610
Launched : 2016
JSM General Surgery Cases and Images
ISSN : 2573-1564
Launched : 2016
JSM Anatomy and Physiology
ISSN : 2573-1262
Launched : 2016
JSM Dental Surgery
ISSN : 2573-1548
Launched : 2016
Annals of Emergency Surgery
ISSN : 2573-1017
Launched : 2016
Annals of Mens Health and Wellness
ISSN : 2641-7707
Launched : 2017
Journal of Preventive Medicine and Health Care
ISSN : 2576-0084
Launched : 2018
Journal of Chronic Diseases and Management
ISSN : 2573-1300
Launched : 2016
Annals of Vaccines and Immunization
ISSN : 2378-9379
Launched : 2014
JSM Heart Surgery Cases and Images
ISSN : 2578-3157
Launched : 2016
Annals of Reproductive Medicine and Treatment
ISSN : 2573-1092
Launched : 2016
JSM Brain Science
ISSN : 2573-1289
Launched : 2016
JSM Biomarkers
ISSN : 2578-3815
Launched : 2014
JSM Biology
ISSN : 2475-9392
Launched : 2016
Archives of Stem Cell and Research
ISSN : 2578-3580
Launched : 2014
Annals of Clinical and Medical Microbiology
ISSN : 2578-3629
Launched : 2014
JSM Pediatric Surgery
ISSN : 2578-3149
Launched : 2017
Journal of Memory Disorder and Rehabilitation
ISSN : 2578-319X
Launched : 2016
JSM Tropical Medicine and Research
ISSN : 2578-3165
Launched : 2016
JSM Head and Face Medicine
ISSN : 2578-3793
Launched : 2016
JSM Cardiothoracic Surgery
ISSN : 2573-1297
Launched : 2016
JSM Bone and Joint Diseases
ISSN : 2578-3351
Launched : 2017
JSM Bioavailability and Bioequivalence
ISSN : 2641-7812
Launched : 2017
JSM Atherosclerosis
ISSN : 2573-1270
Launched : 2016
Journal of Genitourinary Disorders
ISSN : 2641-7790
Launched : 2017
Journal of Fractures and Sprains
ISSN : 2578-3831
Launched : 2016
Journal of Autism and Epilepsy
ISSN : 2641-7774
Launched : 2016
Annals of Marine Biology and Research
ISSN : 2573-105X
Launched : 2014
JSM Health Education & Primary Health Care
ISSN : 2578-3777
Launched : 2016
JSM Communication Disorders
ISSN : 2578-3807
Launched : 2016
Annals of Musculoskeletal Disorders
ISSN : 2578-3599
Launched : 2016
Annals of Virology and Research
ISSN : 2573-1122
Launched : 2014
JSM Renal Medicine
ISSN : 2573-1637
Launched : 2016
Journal of Muscle Health
ISSN : 2578-3823
Launched : 2016
JSM Genetics and Genomics
ISSN : 2334-1823
Launched : 2013
JSM Anxiety and Depression
ISSN : 2475-9139
Launched : 2016
Clinical Journal of Heart Diseases
ISSN : 2641-7766
Launched : 2016
Annals of Medicinal Chemistry and Research
ISSN : 2378-9336
Launched : 2014
JSM Pain and Management
ISSN : 2578-3378
Launched : 2016
JSM Women's Health
ISSN : 2578-3696
Launched : 2016
Clinical Research in HIV or AIDS
ISSN : 2374-0094
Launched : 2013
Journal of Endocrinology, Diabetes and Obesity
ISSN : 2333-6692
Launched : 2013
Journal of Substance Abuse and Alcoholism
ISSN : 2373-9363
Launched : 2013
JSM Neurosurgery and Spine
ISSN : 2373-9479
Launched : 2013
Journal of Liver and Clinical Research
ISSN : 2379-0830
Launched : 2014
Journal of Drug Design and Research
ISSN : 2379-089X
Launched : 2014
JSM Clinical Oncology and Research
ISSN : 2373-938X
Launched : 2013
JSM Bioinformatics, Genomics and Proteomics
ISSN : 2576-1102
Launched : 2014
JSM Chemistry
ISSN : 2334-1831
Launched : 2013
Journal of Trauma and Care
ISSN : 2573-1246
Launched : 2014
JSM Surgical Oncology and Research
ISSN : 2578-3688
Launched : 2016
Annals of Food Processing and Preservation
ISSN : 2573-1033
Launched : 2016
Journal of Radiology and Radiation Therapy
ISSN : 2333-7095
Launched : 2013
JSM Physical Medicine and Rehabilitation
ISSN : 2578-3572
Launched : 2016
Annals of Clinical Pathology
ISSN : 2373-9282
Launched : 2013
Annals of Cardiovascular Diseases
ISSN : 2641-7731
Launched : 2016
Journal of Behavior
ISSN : 2576-0076
Launched : 2016
Annals of Clinical and Experimental Metabolism
ISSN : 2572-2492
Launched : 2016
Clinical Research in Infectious Diseases
ISSN : 2379-0636
Launched : 2013
JSM Microbiology
ISSN : 2333-6455
Launched : 2013
Journal of Urology and Research
ISSN : 2379-951X
Launched : 2014
Journal of Family Medicine and Community Health
ISSN : 2379-0547
Launched : 2013
Annals of Pregnancy and Care
ISSN : 2578-336X
Launched : 2017
JSM Cell and Developmental Biology
ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Clinical Research in Pulmonology
ISSN : 2333-6625
Launched : 2013
Journal of Immunology and Clinical Research
ISSN : 2333-6714
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
Author Information X