De novo germ-line mutation of APC gene in periampullary carcinoma with familial adenomatous polyps – A novel familial case report in South India

AbstractPeriampullary carcinoma is a malignant tumour arising from the ampulla of vater. Adenomatous polyposis coli (APC) gene has a key role in stabilizing β-catenin pathway, in which hypermethylation in APC gene could lead to proteasome degradation of β-catenin. The aim of this case report is to identify the APC gene mutation and its influence on β-catenin pathway in patient with periampullary carcinoma. A 51-year-old woman was diagnosed with yellow discolouration of sclera, passing deep yellow coloured urine and pruritus. A family history of ovarian cancer had been reported in her mother. Her radiological, pathological and laboratory examination confirmed periampullary carcinoma. She underwent whipple's pancreaticoduodenectomy, and the histopathology of the resected specimen showed a well differentiated adenocarcinoma involving the ampulla of vater. Further, the tumour region was subjected to genetic screening by polymerase chain reaction – restriction fragment length polymorphism (PCR-RFLP), cytogenetic analyses such as karyotyping and immunohistochemical techniques. These results showed non-sense mutation in APC gene at codon 1309, chromosomal alterations at 5q21 and irregular accumulation of β-catenin in nuclear membrane. The family history revealed a strong association of ovarian cancer (maternal) with a similar APC gene mutation. We conclude that periampullary carcinoma patient exhibit FAP due to de novo germ-line mutation of APC gene that engenders an inactivation of β-catenine/TCF mediated transcription function, which is linked with a family history of ovarian cancer

A recurrent case of pyruvate dehydrogenase complex deficiency

Pyruvate dehydrogenase complex deficiency is an inherited inborn error of metabolism causing lactic acidosis and several neurological symptoms. Its incidence and prevalence are not known. Here we report about a child with global developmental delay, central hypotonia and dyskinesia. Sanger sequencing was done and found to have homozygous nonsense mutation in exon 4 of PDHX gene causing lactic acidosis. In the next pregnancy selective Sanger variant analysis was carried out and the fetus was also found to be affected with the same genetic defect. Hence medical termination of Pregnancy was carried out. We conclude that early selective genetic testing will prevent further affected births

A preliminary study of the immunogenic response of plant-derived multi-epitopic peptide vaccine candidate of Mycoplasma gallisepticum in chickens

Mycoplasma gallisepticum (MG) is responsible for chronic respiratory disease in avian species, characterized by symptoms like respiratory rales and coughing. Existing vaccines for MG have limited efficacy and require multiple doses. Certain MG cytoadherence proteins (GapA, CrmA, PlpA, and Hlp3) play a crucial role in the pathogen’s respiratory tract colonization and infection. Plant-based proteins and therapeutics have gained attention due to their safety and efficiency. In this study, we designed a 21.4-kDa multi-epitope peptide vaccine (MEPV) using immunogenic segments from cytoadherence proteins. The MEPV’s effectiveness was verified through computational simulations. We then cloned the MEPV, introduced it into the plant expression vector pSiM24-eGFP, and expressed it in Nicotiana benthamiana leaves. The plant-produced MEPV proved to be immunogenic when administered intramuscularly to chickens. It significantly boosted the production of immunoglobulin Y (IgY)-neutralizing antibodies against cytoadherence protein epitopes in immunized chickens compared to that in the control group. This preliminary investigation demonstrates that the plant-derived MEPV is effective in triggering an immune response in chickens. To establish an efficient poultry health management system and ensure the sustainability of the poultry industry, further research is needed to develop avian vaccines using plant biotechnology

Image_1_A preliminary study of the immunogenic response of plant-derived multi-epitopic peptide vaccine candidate of Mycoplasma gallisepticum in chickens.tif

Mycoplasma gallisepticum (MG) is responsible for chronic respiratory disease in avian species, characterized by symptoms like respiratory rales and coughing. Existing vaccines for MG have limited efficacy and require multiple doses. Certain MG cytoadherence proteins (GapA, CrmA, PlpA, and Hlp3) play a crucial role in the pathogen’s respiratory tract colonization and infection. Plant-based proteins and therapeutics have gained attention due to their safety and efficiency. In this study, we designed a 21.4-kDa multi-epitope peptide vaccine (MEPV) using immunogenic segments from cytoadherence proteins. The MEPV’s effectiveness was verified through computational simulations. We then cloned the MEPV, introduced it into the plant expression vector pSiM24-eGFP, and expressed it in Nicotiana benthamiana leaves. The plant-produced MEPV proved to be immunogenic when administered intramuscularly to chickens. It significantly boosted the production of immunoglobulin Y (IgY)-neutralizing antibodies against cytoadherence protein epitopes in immunized chickens compared to that in the control group. This preliminary investigation demonstrates that the plant-derived MEPV is effective in triggering an immune response in chickens. To establish an efficient poultry health management system and ensure the sustainability of the poultry industry, further research is needed to develop avian vaccines using plant biotechnology.</p

Neurotoxicity of pesticides – A link to neurodegeneration

Funding Information: The author Dr. VB would like to thank Bharathiar University for providing the necessary infrastructure facility and the Indian Council of Medical Research DHR-GIA [grant number: GIA/2019/000276/PRCGIA], Government of India, New Delhi for providing necessary help in carrying out this review process. Funding Information: This work was supported by the Indian Council of Medical Research DHR-GIA [grant number: GIA/2019/000276/PRCGIA ], and by the Department of Applied Physics, School of Science, Aalto University , Espoo, Finland. Government of India. Publisher Copyright: © 2022Parkinson's disease (PD) is a neurodegenerative disorder which mainly targets motor symptoms such as tremor, rigidity, bradykinesia and postural instability. The physiological changes occur due to dopamine depletion in basal ganglia region of the brain. PD aetiology is not yet elucidated clearly but genetic and environmental factors play a prominent role in disease occurrence. Despite of various environmental factors, pesticides exposure has been convicted as major candidate in PD pathogenesis. Among various pesticides 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been widely investigated in PD following with paraquat (PQ), maneb (MB), organochlorines (OC) and rotenone. Effect of these pesticides has been suggested to be involved in oxidative stress, alterations in dopamine transporters, mitochondrial dysfunction, α-synuclein (αSyn) fibrillation, and neuroinflammation in PD. The present review discusses the influence of pesticides in neurodegeneration and its related epidemiological studies conducted in PD. Furthermore, we have deliberated the common pesticides involved in PD and its associated genetic alterations and the probable mechanism of them behind PD pathogenesis. Hence, we conclude that pesticides play a prominent role in PD pathogenesis and advance research is needed to investigate the alterations in genetic and mechanistic aspects of PD.Peer reviewe