As an inflammatory disorder, Multiple Sclerosis (MS) causes demyelination, as well as axonal and neuronal injury in the central nervous system (CNS). Several clinical signs may be the indicators of MS among which, Clinically Isolated Syndrome (CIS) is the first symptom caused by the inflammation and demyelination of CNS. CIS is characterized by symptoms such as optic neuritis, brain stem or cerebellar syndrome, spinal cord syndrome, or sometimes cerebral hemispheric dysfunction. So far, metabolic pathways involved in the development of CIS are not fully understood. Therefore, in this study, weighted gene co-expression network analysis (WGCNA) has been used to identify differentially expressed genes in CIS disease and the main pathways associated with it. We grouped differentially expressed genes along with the functionally related genes into large modules to obtain their direct and indirect relationships. The results have identified two new pathways associated with CIS, including riboflavin and histidine metabolism-involved pathways. Riboflavin and histidine metabolism-involved pathways may be considered potential therapeutic goals for CIS management in the future.
{"title":"Riboflavin and Histidine Metabolisms Are Two Key Pathways Related to the Clinically Isolated Syndrome (CIS): a WGCNA-based in silico Analysis","authors":"Mansoor Salehi, Parvaneh Tavakoli Afshar, Zohreh Taherian, Roya Bakhtiyari, Farzaneh Rami, M. Etemadifar","doi":"10.2174/1875692120666230504114225","DOIUrl":"https://doi.org/10.2174/1875692120666230504114225","url":null,"abstract":"\u0000\u0000As an inflammatory disorder, Multiple Sclerosis (MS) causes demyelination, as well as axonal and neuronal injury in the central nervous system (CNS). Several clinical signs may be the indicators of MS among which, Clinically Isolated Syndrome (CIS) is the first symptom caused by the inflammation and demyelination of CNS. CIS is characterized by symptoms such as optic neuritis, brain stem or cerebellar syndrome, spinal cord syndrome, or sometimes cerebral hemispheric dysfunction.\u0000\u0000\u0000\u0000So far, metabolic pathways involved in the development of CIS are not fully understood. Therefore, in this study, weighted gene co-expression network analysis (WGCNA) has been used to identify differentially expressed genes in CIS disease and the main pathways associated with it.\u0000\u0000\u0000\u0000We grouped differentially expressed genes along with the functionally related genes into large modules to obtain their direct and indirect relationships.\u0000\u0000\u0000\u0000The results have identified two new pathways associated with CIS, including riboflavin and histidine metabolism-involved pathways.\u0000\u0000\u0000\u0000Riboflavin and histidine metabolism-involved pathways may be considered potential therapeutic goals for CIS management in the future.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88392226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-01DOI: 10.2174/187569212001230613152539
Muntaser E. Ibrahim
{"title":"Meet the Editorial Board Member","authors":"Muntaser E. Ibrahim","doi":"10.2174/187569212001230613152539","DOIUrl":"https://doi.org/10.2174/187569212001230613152539","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80134708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-22DOI: 10.2174/1875692120666230222110736
Reza Nekouian, Atiyeh Mohamadi, Seyyed Amir Yasin Ahmadi
Papillary Thyroid Carcinoma (PTC) is the most common subtype of thyroid cancer that is the most prevalent in the endocrine system. According to worldwide reports, its prevalence rate has been increasing in recent decades. The Discovery of DNA sequencing methods and molecular diagnostic techniques provides an insight into the understanding of PTC molecular biology and as well as in thyroidology, which opens a new perspective in finding molecular markers. Aligning cytological diagnostic methods with molecular behavior studies creates promising tools for better decision-making strategies for preoperative conditions to distinguish between benign from malignant thyroid nodules in challenging cases and limit unnecessary surgeries. Extensive studies have been performed on identifying the genes involved in PTC development and their prognosis. Currently, clinical and pathological features of the tumour (such as size, extrathyroid and lymph node invasion, and capsular invasion) are used to predict the prognosis of papillary thyroid cancer. In this review, we tried to summarize fundamental signaling pathways affecting PTC and the most important genetic alterations, including point mutations in proto-oncogenes and chromosomal rearrangements, as well as up/down-regulation of certain micro RNAs (miRNA) as an epigenetic change. Briefly, some of the most commonly altered genes in PTC are BRAF, RAS, RET, PAX8, PPARγ, and miRNAs like mir-146b, mir-221, mir-222, and mir-181b.
{"title":"Papillary thyroid carcinoma: A narrative review on the most important genetic and epigenetic alterations","authors":"Reza Nekouian, Atiyeh Mohamadi, Seyyed Amir Yasin Ahmadi","doi":"10.2174/1875692120666230222110736","DOIUrl":"https://doi.org/10.2174/1875692120666230222110736","url":null,"abstract":"\u0000\u0000Papillary Thyroid Carcinoma (PTC) is the most common subtype of thyroid cancer that is the most prevalent in the endocrine system. According to worldwide reports, its prevalence rate has been increasing in recent decades. The Discovery of DNA sequencing methods and molecular diagnostic techniques provides an insight into the understanding of PTC molecular biology and as well as in thyroidology, which opens a new perspective in finding molecular markers. Aligning cytological diagnostic methods with molecular behavior studies creates promising tools for better decision-making strategies for preoperative conditions to distinguish between benign from malignant thyroid nodules in challenging cases and limit unnecessary surgeries. Extensive studies have been performed on identifying the genes involved in PTC development and their prognosis. Currently, clinical and pathological features of the tumour (such as size, extrathyroid and lymph node invasion, and capsular invasion) are used to predict the prognosis of papillary thyroid cancer. In this review, we tried to summarize fundamental signaling pathways affecting PTC and the most important genetic alterations, including point mutations in proto-oncogenes and chromosomal rearrangements, as well as up/down-regulation of certain micro RNAs (miRNA) as an epigenetic change. Briefly, some of the most commonly altered genes in PTC are BRAF, RAS, RET, PAX8, PPARγ, and miRNAs like mir-146b, mir-221, mir-222, and mir-181b.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"88 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90921978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-13DOI: 10.2174/1875692120666230213111629
I. Chaoui, Raja Benzeid, Amina Gihbid, N. Benchekroun, N. Tawfiq, A. Benider, Mohammed Attaleb, A. Filali Maltouf, M. El Mzibri, M. Khyatti
Nasopharyngeal cancer [NPC] is one of the most common head and neck cancers. NPC differs significantly from other cancers in its etiology, epidemiology, clinical behavior, and treatment. Being highly radiosensitive, the standard treatment for NPC is radiotherapy. However, radioresistance hampers the success of treatment and may cause local recurrence and distant metastases in NPC patients. In this review, we discuss the updated protocols for NPC diagnosis and treatment based on recent literature with an emphasis on the mechanisms of radioresistance at the molecular level with a special focus on genetic and epigenetic events, affecting genes involved in xenobiotic detoxification and DNA repair. We also highlight the importance of some cellular and Epstein Barr viral miRNAs targeting specific DNA repair factors and consequently promoting NPC radioresistance. These molecular markers may serve as promising tools for diagnosis, prognosis, and radioresistance prediction to guide theranostics of patients with NPC in the future.
{"title":"Recent advances in Nasopharyngeal cancer management: from diagnosis to theranostics","authors":"I. Chaoui, Raja Benzeid, Amina Gihbid, N. Benchekroun, N. Tawfiq, A. Benider, Mohammed Attaleb, A. Filali Maltouf, M. El Mzibri, M. Khyatti","doi":"10.2174/1875692120666230213111629","DOIUrl":"https://doi.org/10.2174/1875692120666230213111629","url":null,"abstract":"\u0000\u0000Nasopharyngeal cancer [NPC] is one of the most common head and neck cancers. NPC differs significantly from other cancers in its etiology, epidemiology, clinical behavior, and treatment. Being highly radiosensitive, the standard treatment for NPC is radiotherapy. However, radioresistance hampers the success of treatment and may cause local recurrence and distant metastases in NPC patients. In this review, we discuss the updated protocols for NPC diagnosis and treatment based on recent literature with an emphasis on the mechanisms of radioresistance at the molecular level with a special focus on genetic and epigenetic events, affecting genes involved in xenobiotic detoxification and DNA repair. We also highlight the importance of some cellular and Epstein Barr viral miRNAs targeting specific DNA repair factors and consequently promoting NPC radioresistance. These molecular markers may serve as promising tools for diagnosis, prognosis, and radioresistance prediction to guide theranostics of patients with NPC in the future.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83901556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-06DOI: 10.2174/1875692120666230206141327
Alexander E. Jacobsen, Antje Jüngling, Corinna Gorges, M. Eidens
Abacavir is used in the treatment of HIV-infected patients. A hypersensitive reaction (HSR) occurs in about 5-8% of patients treated with Abacavir. The HLA-B*57:01 allele is a valuable predictor for HSR and its screening is mandatory prior to treatment with Abacavir. Abacavir is used in the treatment of HIV-infected patients. A hypersensitive reaction (HSR) occurs in about 5-8% of patients treated with Abacavir. The HLA-B*57:01 allele is a valuable predictor for HSR and its screening is mandatory prior treatment with Abacavir. Current screening methods require considerable investments for equipment. In order to lower the required investments and enable physician practices to perform the screening in a point-of-care (PoC) setting, our objective was to develop a novel isothermal genetic rapid test that requires a minimal setup cost, does not require specific training and thus is suitable for a physician practice setting. Current screening methods require considerable investments for equipment. In order to lower the required investments and enable physician practices to perform the screening in a point-of-care (PoC) setting, our objective was to develop an isothermal recombinase polymerase amplification (RPA) for the specific amplification of the HLA-B*57:01 allele and detection via lateral flow dipstick. We developed an isothermal recombinase polymerase amplification (RPA) for the specific amplification of the HLA-B*57:01 allele using allele-specific primers coupled to Biotin. Primers specific for human lactase gene, coupled to Digoxigenin, were used as an internal amplification control (IAC). Lateral flow dipstick provided rapid and accurate detection of HLA-B*57:01 allele and IAC via the respective antibodies sprayed on the strips surface. The reference method identified the HLA-B*57:01 allele in the reference sample, in 2 out of 28 buccal swab samples and in 2 out of 13 blood samples. The initial isothermal RPA resulted in unspecific amplification of the HLA-B*57:01 allele. By further optimization steps the specific amplification of the allele and the detection on lateral flow dipstick was observed. The newly developed isothermal RPA was validated. The method developed fulfils the requirements for a genetically based PoC screening system for the HLA-B*57:01 variant, requiring a minimal investment for a heating block and a pipette.
{"title":"Development of an Isothermal Point-of-Care Genetic rapid test for the\u0000detection of the HLA-B*57:01 Allele, a predictor for Hypersensitivity reaction caused by Abacavir, for stratifying patients for Antiretroviral Abacavir HIV therapy","authors":"Alexander E. Jacobsen, Antje Jüngling, Corinna Gorges, M. Eidens","doi":"10.2174/1875692120666230206141327","DOIUrl":"https://doi.org/10.2174/1875692120666230206141327","url":null,"abstract":"\u0000\u0000Abacavir is used in the treatment of HIV-infected patients. A hypersensitive reaction (HSR) occurs in about 5-8% of patients treated with Abacavir. The HLA-B*57:01 allele is a valuable predictor for HSR and its screening is mandatory prior to treatment with Abacavir.\u0000\u0000\u0000\u0000Abacavir is used in the treatment of HIV-infected patients. A hypersensitive reaction (HSR) occurs in about 5-8% of patients treated with Abacavir. The HLA-B*57:01 allele is a valuable predictor for HSR and its screening is mandatory prior treatment with Abacavir.\u0000\u0000\u0000\u0000Current screening methods require considerable investments for equipment. In order to lower the required investments and enable physician practices to perform the screening in a point-of-care (PoC) setting, our objective was to develop a novel isothermal genetic rapid test that requires a minimal setup cost, does not require specific training and thus is suitable for a physician practice setting.\u0000\u0000\u0000\u0000Current screening methods require considerable investments for equipment. In order to lower the required investments and enable physician practices to perform the screening in a point-of-care (PoC) setting, our objective was to develop an isothermal recombinase polymerase amplification (RPA) for the specific amplification of the HLA-B*57:01 allele and detection via lateral flow dipstick.\u0000\u0000\u0000\u0000We developed an isothermal recombinase polymerase amplification (RPA) for the specific amplification of the HLA-B*57:01 allele using allele-specific primers coupled to Biotin. Primers specific for human lactase gene, coupled to Digoxigenin, were used as an internal amplification control (IAC). Lateral flow dipstick provided rapid and accurate detection of HLA-B*57:01 allele and IAC via the respective antibodies sprayed on the strips surface.\u0000\u0000\u0000\u0000The reference method identified the HLA-B*57:01 allele in the reference sample, in 2 out of 28 buccal swab samples and in 2 out of 13 blood samples. The initial isothermal RPA resulted in unspecific amplification of the HLA-B*57:01 allele. By further optimization steps the specific amplification of the allele and the detection on lateral flow dipstick was observed. The newly developed isothermal RPA was validated.\u0000\u0000\u0000\u0000The method developed fulfils the requirements for a genetically based PoC screening system for the HLA-B*57:01 variant, requiring a minimal investment for a heating block and a pipette.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84982429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-26DOI: 10.2174/1875692120666230126110252
J. Parkash, Arpita Banerjee, Randeep Singh, Nymphaea Arora, Tania Arora, Vikash Prashar, P. Godara, Arti Sharma, H. Changotra
Nitric oxide synthase (NOS) is an enzyme that catalyzes the synthesis of nitric oxide (NO) from L-arginine. It has three isoforms: (1) neuronal NOS (nNOS or NOS1), which participates in neural transmission; (2) inducible NOS (iNOS or NOS2), which produces NO in macrophages; and (3) endothelial NOS (eNOS or NOS3) that regulates blood pressure. The eNOS is mainly expressed in blood vessels and is a crucial regulator of endothelial homeostasis. The present study aimed to unravel the role of eNOS in different signaling pathways and its involvement as a therapeutic target in various neurodegenerative disorders. This study used various in silico methods for comprehensive genomic analysis of eNOS in 16 organisms from 7 different phyla. Prediction of conserved domains and evolutionary relationship for eNOS among 16 organisms was made. Various physical and chemical parameters, signal peptides, and transmembrane regions that helped understand its functional relevance were also studied. Three transcription factor binding sites (TFBS), i.e., CP2, AR, and LDSPOLYA, were identified in human eNOS, while ATF1, T3R, and STAT1 were predicted in mouse eNOS. Transcription factors were identified for each regulatory region in human as well as mouse eNOS. eNOS protein was predicted to harbor 14 different post-translational modification (PTM) sites, most of which have phosphorylation (serine followed by threonine and tyrosine phosphorylation) followed by sumoylation and palmitoylation among all the organisms used in the current study. However, human eNOS has a relatively lower number of PTM sites for tyrosine phosphorylation. Structures of eNOS isoform, consistent with available biochemical and structural data, provide substantial insight into the NOS conformational changes, which give in-depth knowledge of the mechanism of eNOS, and will be helpful for better understanding the role of eNOS in pathophysiology.
{"title":"The Comparative Genomics and Network Analysis of eNOS by Using Different Bioinformatics Approaches","authors":"J. Parkash, Arpita Banerjee, Randeep Singh, Nymphaea Arora, Tania Arora, Vikash Prashar, P. Godara, Arti Sharma, H. Changotra","doi":"10.2174/1875692120666230126110252","DOIUrl":"https://doi.org/10.2174/1875692120666230126110252","url":null,"abstract":"\u0000\u0000Nitric oxide synthase (NOS) is an enzyme that catalyzes the synthesis of nitric oxide (NO) from L-arginine. It has three isoforms: (1) neuronal NOS (nNOS or NOS1), which participates in neural transmission; (2) inducible NOS (iNOS or NOS2), which produces NO in macrophages; and (3) endothelial NOS (eNOS or NOS3) that regulates blood pressure. The eNOS is mainly expressed in blood vessels and is a crucial regulator of endothelial homeostasis.\u0000\u0000\u0000\u0000The present study aimed to unravel the role of eNOS in different signaling pathways and its involvement as a therapeutic target in various neurodegenerative disorders.\u0000\u0000\u0000\u0000This study used various in silico methods for comprehensive genomic analysis of eNOS in 16 organisms from 7 different phyla. Prediction of conserved domains and evolutionary relationship for eNOS among 16 organisms was made. Various physical and chemical parameters, signal peptides, and transmembrane regions that helped understand its functional relevance were also studied.\u0000\u0000\u0000\u0000Three transcription factor binding sites (TFBS), i.e., CP2, AR, and LDSPOLYA, were identified in human eNOS, while ATF1, T3R, and STAT1 were predicted in mouse eNOS. Transcription factors were identified for each regulatory region in human as well as mouse eNOS. eNOS protein was predicted to harbor 14 different post-translational modification (PTM) sites, most of which have phosphorylation (serine followed by threonine and tyrosine phosphorylation) followed by sumoylation and palmitoylation among all the organisms used in the current study. However, human eNOS has a relatively lower number of PTM sites for tyrosine phosphorylation.\u0000\u0000\u0000\u0000Structures of eNOS isoform, consistent with available biochemical and structural data, provide substantial insight into the NOS conformational changes, which give in-depth knowledge of the mechanism of eNOS, and will be helpful for better understanding the role of eNOS in pathophysiology.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"2001 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88343329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-24DOI: 10.2174/1875692120666221124121316
M. Banerjee, Atar Singh Kushwah, P. Vats, K. Usman
Type 2 diabetes mellitus (T2DM) is a complex metabolic disease that is caused by insulin dysfunction. It is an output of oxidative stress that results from defective redox reactions and increased reactive metabolites (RMs) and is neutralized by antioxidant enzymes. It has been reported that decreased levels of antioxidant enzymes are due to genetic alterations in the respective genes. Therefore, the present study has undertaken a genetic analysis of antioxidant genes and their interaction in the family to assess T2DM risk. This study aimed to investigate the individual susceptibility>risk to T2DM using antioxidant gene variants and their interactions in family members with a diabetic history. Genotypic analysis of antioxidant genes was done by polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP), haplotype analysis, and gene-gene interactions using statistical tools. Pedigrees were constructed by face-to-face interviews with members of nine families. Genotypes AT (CAT-21A>T), IV (GSTP1+313(105I>V), and CT (GPx1 +599C>T) were found to be frequent in diabetic individuals. For instance, in one family, if only the mother had diabetes, all siblings were found to have the risk genotypes AT (CAT21A>T) and CT (GPx1 +599C>T) with 2.12- and 2.11-folds risk of developing T2DM. The risk haplotypes, NNV (GSTM1 N>P(Null>Present), GSTT1 N>P(Null>Present), GSTP1105I>V and TCC (CAT-21A>T, SOD2+47C>T, GPx1+599C>T) were observed in most of the diabetic individuals and non-diabetics possessing the risk haplotypes manifested altered BMI. The present study suggests that the GSTP1105I>V, CAT-21A>T, SOD2+47C>T and GPx1+599C>T gene variants can be prognostic biomarkers for the assessment of T2DM risk in healthy individuals.
{"title":"Risk prediction of type 2 diabetes mellitus (T2DM) in Indian families using antioxidant gene variants","authors":"M. Banerjee, Atar Singh Kushwah, P. Vats, K. Usman","doi":"10.2174/1875692120666221124121316","DOIUrl":"https://doi.org/10.2174/1875692120666221124121316","url":null,"abstract":"\u0000\u0000Type 2 diabetes mellitus (T2DM) is a complex metabolic disease\u0000that is caused by insulin dysfunction. It is an output of oxidative stress that results from defective redox reactions and increased reactive metabolites (RMs) and is neutralized by antioxidant enzymes. It has been reported that decreased levels of antioxidant enzymes are due\u0000to genetic alterations in the respective genes. Therefore, the present study has undertaken a\u0000genetic analysis of antioxidant genes and their interaction in the family to assess T2DM\u0000risk.\u0000\u0000\u0000\u0000This study aimed to investigate the individual susceptibility>risk to T2DM using\u0000antioxidant gene variants and their interactions in family members with a diabetic history.\u0000\u0000\u0000\u0000Genotypic analysis of antioxidant genes was done by polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP), haplotype analysis, and gene-gene\u0000interactions using statistical tools. Pedigrees were constructed by face-to-face interviews\u0000with members of nine families.\u0000\u0000\u0000\u0000Genotypes AT (CAT-21A>T), IV (GSTP1+313(105I>V), and CT (GPx1\u0000+599C>T) were found to be frequent in diabetic individuals. For instance, in one family, if\u0000only the mother had diabetes, all siblings were found to have the risk genotypes AT (CAT21A>T) and CT (GPx1 +599C>T) with 2.12- and 2.11-folds risk of developing T2DM. The\u0000risk haplotypes, NNV (GSTM1 N>P(Null>Present), GSTT1 N>P(Null>Present),\u0000GSTP1105I>V and TCC (CAT-21A>T, SOD2+47C>T, GPx1+599C>T) were observed in\u0000most of the diabetic individuals and non-diabetics possessing the risk haplotypes manifested\u0000altered BMI.\u0000\u0000\u0000\u0000The present study suggests that the GSTP1105I>V, CAT-21A>T,\u0000SOD2+47C>T and GPx1+599C>T gene variants can be prognostic biomarkers for the assessment of T2DM risk in healthy individuals.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83521743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-24DOI: 10.2174/1875692120666221124113404
N. Rezaei, S. Khanmohammadi, S. Zoghi, Elham Rayzan, S. Shahkarami, R. Jimenez Heredia, A. Frohne, Simin Seyedpour, K. Boztug
Juvenile myelomonocytic leukemia (JMML) is a rare childhood disease characterized by hepatosplenomegaly, monocytosis, anemia, increased white blood cell count, thrombocytopenia, skin infiltration, and elevated fetal hemoglobin. Mutation in specific genes, including KRAS, NRAS, PTPN11, and NF1, can lead to the development of JMML. A two-year-old boy with a history of inguinal abscess at the age of 12 months and surgery due to infectious lymphadenitis was referred to the hospital. His parents also reported a history of oral candidiasis, recurrent otitis media, and lymphadenopathy in the patient. The physical examination showed splenomegaly, macular rash, lymphadenopathy in the neck region, and rashes in the inguinal region and on the hands and feet. Laboratory and flow cytometry data showed lymphocytosis, low hemoglobin, thrombocytopenia, monocytosis, eosinophilia, and a shift to the left in the peripheral blood. The bone marrow aspiration showed a cellular marrow with myeloid hyperplasia. Whole-exome sequencing revealed a rare heterozygous ENST00000351677.2:c.1508G>C, p.Gly503Ala variant in PTPN11. The patient was diagnosed with JMML but, unfortunately, passed away. We report a rare heterozygous mutation in the PTPN11 gene in a two-year-old boy diagnosed with JMML. This uncommon mutation should be considered in the mutational screening protocol of JMML. Management of JMML with RAS pathway targeted therapy may also have promising results and needs further investigations.
{"title":"A Rare PTPN11 Mutation in a Patient with Juvenile Myelomonocytic\u0000Leukemia: A Case Report","authors":"N. Rezaei, S. Khanmohammadi, S. Zoghi, Elham Rayzan, S. Shahkarami, R. Jimenez Heredia, A. Frohne, Simin Seyedpour, K. Boztug","doi":"10.2174/1875692120666221124113404","DOIUrl":"https://doi.org/10.2174/1875692120666221124113404","url":null,"abstract":"\u0000\u0000Juvenile myelomonocytic leukemia (JMML) is a rare childhood disease characterized by hepatosplenomegaly, monocytosis, anemia, increased white blood cell\u0000count, thrombocytopenia, skin infiltration, and elevated fetal hemoglobin. Mutation in specific\u0000genes, including KRAS, NRAS, PTPN11, and NF1, can lead to the development of JMML.\u0000\u0000\u0000\u0000A two-year-old boy with a history of inguinal abscess at the age of 12\u0000months and surgery due to infectious lymphadenitis was referred to the hospital. His parents\u0000also reported a history of oral candidiasis, recurrent otitis media, and lymphadenopathy in\u0000the patient. The physical examination showed splenomegaly, macular rash, lymphadenopathy in the neck region, and rashes in the inguinal region and on the hands and feet. Laboratory and flow cytometry data showed lymphocytosis, low hemoglobin, thrombocytopenia,\u0000monocytosis, eosinophilia, and a shift to the left in the peripheral blood. The bone marrow\u0000aspiration showed a cellular marrow with myeloid hyperplasia. Whole-exome sequencing\u0000revealed a rare heterozygous ENST00000351677.2:c.1508G>C, p.Gly503Ala variant in\u0000PTPN11. The patient was diagnosed with JMML but, unfortunately, passed away.\u0000\u0000\u0000\u0000We report a rare heterozygous mutation in the PTPN11 gene in a two-year-old\u0000boy diagnosed with JMML. This uncommon mutation should be considered in the mutational screening protocol of JMML. Management of JMML with RAS pathway targeted\u0000therapy may also have promising results and needs further investigations.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88380048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-30DOI: 10.2174/1875692119666220930161000
K. Srivastava, Shelly Aggarwal, R. Narang, D. Saluja
PCSK9 (Proprotein convertase subtilisin/kexin type 9) plays a key role in cholesterol homeostasis and Coronary artery disease (CAD). Many studies have extrapolated the association of PCSK9 gene with low density lipoprotein cholesterol (LDL-C) levels and CAD but with contradicting results. There is no such study available stating the intergenotypic variations in the levels of expression of PCSK9 and LDL-C and their correlations with CAD risk factors in patients with CAD. We aim to explore the association of PCSK9 A/G (rs505151) polymorphism and its expression at mRNA and protein level in patients with CAD. Additionally, it is investigated how the levels of LDL-C, PCSK9, BMI, and systolic blood pressure (SBP) in patients with CAD and in healthy participants relate to the PCSK9 intergenotypic variation. Angiographically confirmed CAD patients [n=250] and controls [n=250] were genotyped by PCR followed by RFLP techniques. Real time PCR and Western Blot methods were used to investigate PCSK9's differential expression. Odds ratio being the index of association revealed a statistically significant association of PCSK9 A/G (rs505151), A Vs G= 4.94 [1.37-7.79] polymorphism with CAD. In patients with the GG genotype, there is a correlation between higher PCSK9 gene expression and circulating LDL-C levels. Our study shows a significant association of PCSK9 gene polymorphism with CAD. We also observed an increased expression of PCSK9 gene in patients with G allele. In our study, PCSK9 A/G (rs505151) gene and LDL-C emerged as independent risk factors. To determine whether upregulated PCSK9 gene expression can act as a prognostic marker for CAD, more follow-up research is required.
PCSK9(蛋白转化酶枯草素/ keexin 9型)在胆固醇稳态和冠状动脉疾病(CAD)中起关键作用。许多研究推断PCSK9基因与低密度脂蛋白胆固醇(LDL-C)水平和CAD之间存在关联，但结果却相互矛盾。目前还没有这样的研究表明在冠心病患者中PCSK9和LDL-C表达水平的基因型差异及其与冠心病危险因素的相关性。我们旨在探讨PCSK9 A/G (rs505151)多态性与CAD患者mRNA和蛋白水平表达的关系。此外，还研究了冠心病患者和健康参与者的LDL-C、PCSK9、BMI和收缩压(SBP)水平与PCSK9基因型变异的关系。血管造影确诊的冠心病患者[n=250]和对照组[n=250]分别采用PCR和RFLP技术进行基因分型。采用Real time PCR和Western Blot方法检测PCSK9的差异表达。比值比作为关联指标显示PCSK9 a /G (rs505151)多态性与CAD的相关性具有统计学意义，a Vs G= 4.94[1.37 ~ 7.79]。在GG基因型患者中，较高的PCSK9基因表达与循环LDL-C水平之间存在相关性。我们的研究表明PCSK9基因多态性与CAD有显著关联。我们还观察到PCSK9基因在G等位基因患者中的表达增加。在我们的研究中，PCSK9 A/G (rs505151)基因和LDL-C成为独立的危险因素。为了确定PCSK9基因表达上调是否可以作为CAD的预后标志物，还需要更多的后续研究。
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Pub Date : 2022-09-26DOI: 10.2174/1875692119666220926150315
S. Chakrabarti, Upinder Kaur, Vandana Dwiivedi, Alok Singh, Ashutosh Kumar Singh, A. Pandey, Kumudini Acharya
This pilot study aimed to make head-to-head comparisons of multiple classes of drugs used in the management of neuropathic pain in North Indian older adult patients presenting to the geriatric clinic of a tertiary medical institution Chronic neuropathic pain is a condition affecting nearly one third of older adults. There is paucity of data on head-to-head comparisons of drugs used in neuropathic pain in older adults. Real world studies may be a useful tool to study diverse neuropathic pain medications in this population. The study objective was to measure NPRS (numeric pain rating scale), GDS (geriatric depression scale), IADL (instrumental activities of daily living), HMSE (Hindi mental state examination) scores at baseline, and 4- and 12-week follow-ups in all older adults patients receiving neuropathic pain medications. A prospective observational study was conducted involving older adult patients ≥ 50 years of age with painful peripheral neuropathy of any etiology (n=60; mean age 63±8.4 years). The patients received either gabapentin, pregabalin, duloxetine, amitriptyline, or methyl-cobalamin complex. NPRS, GDS, IADL, and HMSE scores were measured at baseline and post-therapy. All groups except amitriptyline showed statistically significant improvement in NPRS at 4 weeks and 12 weeks compared to baseline. 30% response rate at 4 weeks was maximum for pregabalin (72%) and 50% response rate at 12 weeks was maximum for gabapentin (58%). Numerically maximum improvement in depression was seen with duloxetine. There was no statistically significant difference in the measured parameters between the drug groups across time. Mean daily dose was 172 mg (gabapentin group), 75 mg (pregabalin group) and 20 mg (duloxetine group). The adverse drug reaction rate was 10.5%. All drug groups showed beneficial effects on neuropathic pain at much lower doses than those described in the literature. The effectiveness at these low doses and the lower rates of adverse effects sets the foundation for larger studies in the future in diverse ethnic and aged populations.
{"title":"A real-world pilot observational study of neuropathic pain medications in older adult patients in North India","authors":"S. Chakrabarti, Upinder Kaur, Vandana Dwiivedi, Alok Singh, Ashutosh Kumar Singh, A. Pandey, Kumudini Acharya","doi":"10.2174/1875692119666220926150315","DOIUrl":"https://doi.org/10.2174/1875692119666220926150315","url":null,"abstract":"\u0000\u0000This pilot study aimed to make head-to-head comparisons of multiple classes\u0000of drugs used in the management of neuropathic pain in North Indian older adult patients presenting to the geriatric clinic of a tertiary medical institution\u0000\u0000\u0000\u0000Chronic neuropathic pain is a condition affecting nearly one third of older\u0000adults. There is paucity of data on head-to-head comparisons of drugs used in neuropathic pain\u0000in older adults. Real world studies may be a useful tool to study diverse neuropathic pain medications in this population.\u0000\u0000\u0000\u0000The study objective was to measure NPRS (numeric pain rating scale), GDS (geriatric depression scale), IADL (instrumental activities of daily living), HMSE (Hindi mental\u0000state examination) scores at baseline, and 4- and 12-week follow-ups in all older adults patients receiving neuropathic pain medications.\u0000\u0000\u0000\u0000A prospective observational study was conducted involving older adult patients ≥\u000050 years of age with painful peripheral neuropathy of any etiology (n=60; mean age 63±8.4\u0000years). The patients received either gabapentin, pregabalin, duloxetine, amitriptyline, or methyl-cobalamin complex. NPRS, GDS, IADL, and HMSE scores were measured at baseline\u0000and post-therapy.\u0000\u0000\u0000\u0000All groups except amitriptyline showed statistically significant improvement in\u0000NPRS at 4 weeks and 12 weeks compared to baseline. 30% response rate at 4 weeks was maximum for pregabalin (72%) and 50% response rate at 12 weeks was maximum for gabapentin\u0000(58%). Numerically maximum improvement in depression was seen with duloxetine. There\u0000was no statistically significant difference in the measured parameters between the drug groups\u0000across time. Mean daily dose was 172 mg (gabapentin group), 75 mg (pregabalin group) and\u000020 mg (duloxetine group). The adverse drug reaction rate was 10.5%.\u0000\u0000\u0000\u0000All drug groups showed beneficial effects on neuropathic pain at much lower\u0000doses than those described in the literature. The effectiveness at these low doses and the lower\u0000rates of adverse effects sets the foundation for larger studies in the future in diverse ethnic and\u0000aged populations.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"92 5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89855966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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