The challenge in managing patients with mitochondrial diseases is in its complex nature as exemplified in the inheritance pattern and clinical presentation of mitochondrial diseases. Besides involvement of the nuclear genes, mitochondrial genes independently or together add to the complexity. Transmission of mitochondrial genome mutations by maternal inheritance and presence of heteroplasmy, high mitochondrial mutation rates and absence of introns poses problems in diagnosis and protocols for identification, treatment, prevention and management of the patients. With the use of advanced techniques including next generation sequencing to simultaneously screen multiple genes for alterations, identification of targets for therapy and better patient management is envisaged. The current review attempts to understand the role of mitochondrial genome in complex diseases and the utility of technological advances in diagnosis of mitochondrial diseases.

The 26S proteasome is the major protease machinery in eukaryotic cells responsible for spatio-temporally regulated turnover of the proteome and therefore critical to the maintenance of homeostasis. These act not only as efficient garbage disposal units for abnormal/misfolded, denatured and oxidised proteins, but, are crucial for irreversible termination of key cellular process regulation of various check points. Replication, transcription, translation, antigen processing, maintenance of stemness, development and differentiation are several of the functions and processes regulated by the proteasomes. The 2.5-megadalton structure of the eukaryotic proteasome is very complex and is assembled from 66 polypeptides with 33 structurally unique. The biogenesis of the multi subunit architecture is regulated by dedicated chaperones which orchestrate the assembly of intricate and complex structure. The current review focuses on four chaperones PSMD9 (Nas2), PSMD10 (Nas6), PAAF1 (Rpn14) and S5B (Hsm3) responsible for the assembly. The structure of the chaperones, molecular details of interaction of the individual chaperones with subunits of the proteasome during the process of assembly, role in hierarchical steps leading to assembly, recent evidences for the unprecedented role of some of these proteins (PSMD9 and PSMD10) in other physiological processes will be summarized. In addition, potential of two chaperones as targets for development of inhibitors of proteasome function will be explored.

Selenium, a micronutrient and an active constituent of important redox enzymes like glutathione peroxidase (GPx) and thioredoxin reductase (TrxR), has been investigated extensively by researchers all over the world for the last four to five decades. Both inorganic and organic selenium compounds are being evaluated as probable drugs or adjuvants for many viral infections and chronic diseases like cancer. Several clinical trials in cancer patients have confirmed that selenium supplementation helps in recovering from cancer therapy associated side effects and selenium itself does not interfere in cancer therapy. Efforts are on to develop new selenium compounds with anti-cancer properties. These aspects will be discussed in this article.

Endogenous and exogenous hormones influence breast cancer risk including estrogen biosynthesis pathway, vitamin D receptor pathway, and the androgen receptor pathway. Genes involved in these pathways are CYP17, which encodes an enzyme involved in estradiol and testosterone synthesis, androgen receptor (AR), which binds testosterone and DHT and regulates breast cell growth and the vitamin D receptor (VDR), which binds vitamin D and down-regulates breast growth.The current study was proposed to determine whether polymorphisms in the CAG repeat in exon 1 of AR, MspAI T > C substitution of CYP17, and ApaI, 7aqI, poly-A repeat in the VDR gene contribute to breast cancer risk. Logistic regression models were used to evaluate individual and joint contributions of genotypes to breast cancer risk.Seventy (70) breast cancer patients and eighty healthy women (80) were recruited for the study. PCR based RFLP and fragment analysis assays were used to determine genotypes of hormone metabolizing genes. Considering CYP17 A2 allele, VDR Poly-(A) L, and AR ≥ 20 CAG repeats as high risk alleles, a multigenic model of breast cancer susceptibility was developed to identify women who carry a combination of alleles to put them at relatively higher risk to develop breast cancer. All the high-risk genotypes were positively associated with risk. The risk among women carrying three high-risk alleles was OR:4.68 [95% confidence interval (CI), 0.77-28.0; p for trend = 0.10] compared with those who carried none. The conditional logistic regression analysis revealed that the heterozygous TC genotype for CYP17 and AR1AR2 of AR, imparted significantly fourfold risk for the breast cancer risk, in comparison to the referent genotype TT and AR1AR1 [adjusted ORs:3.705(1.236,11.106), p = 0.019] and [4.391(1.324,14.557), p = 0.016], respectively. Gene X Gene interaction showed that the combinations TC*AA, TC*Aa, TC*aa and CC*Aa imparted significantly four to fifteen fold more risk for the breast cancer [(4.377 (1.159, 16.520), p = 0.029); 4.041(1.092, 14.956), p = 0.036); (15.071(0.975, 232.81), p = 0.052); (4.151(1.053, 16.371), p = 0.042), respectively)]. Genes involved in hormone synthesis and metabolizing pathway may play a role in breast cancer development as supported by the multigenic model of breast cancer susceptibility.

Benign Prostate Hyperplasia (BPH) pathogenesis exhibitsinter-individual variation in the genome as polymorphisms in the steroid hormone genes AR, PSA (KLK) and ER-β profound effects in altering BPH disease progression rate. Single nucleotide polymorphisms (SNPs) designated 1754 A/G exon-1 in AR, Promotor-158 A/G in PSA(KLK) and 1730 A/G 3’UTR in Exon-8 in ER-β have been associated with BPH pathogenesis. In the current study, AR-1754 A/G exon-1, PSA-ARE1 Promotor-158 A/G and 1730 A/G 3’UTR in Exon-8 in ER-β were analysed in Indian population.The polymorphisms in BPH patients and healthy individuals were evaluated by PCR, RFLP–PCR and genotype–phenotype correlation. In the study AR and ER-β SNPs demonstrated significant association [55.7% (OR 3.0 (95% CI 1.67–5.46) (p 0.0002)] and [52.6 % (OR 6.5, 95% CI 3.27–12.74) (p 0.0001)] with BPH pathogenesis in patients as compared to control. With both the polymorphisms indicating a trend towards an association of the G allele with an increased risk of BPH pathogenesis. The A/G genotype frequency of PSA was 54 % in patients and was not associated with BPH pathogenesis. Further genotype–phenotype correlation study has provided evidence that gene–gene interactions play an important role in the etiology of BPH. Although susceptibility to pathogenesis cannot be dependent on a single or small number of genetic variants, it is noteworthy that AR, PSA and ER-β variants have been correlated globally with BPH pathogenesis. Hence, the higher frequency of AR and ER-β variants in the Indian population may be critical in BPH pathogenesis.

Modified baculoviruses containing a mammalian promoter, known as BacMam, have emerged as a key method for labeling diverse cell types, owing to its high transduction efficiencies, minimal cytopathic effects and the ability to carry DNA fragments larger than 40 KB. The transient expression without viral replication or integration into the mammalian genome makes BacMam an ideal method to label primary and adult stem cells. In the current study, we describe how BacMam enables efficient transduction and robust gene expression in neural stem cells (NSC) and progenitor cells. Utilizing the H9 human embryonic stem cell (hESC), we generated neurospheres, neural rosettes and Neural Stem Cells (NSC) and transduced them with BacMam 2.0 GFP. Commercially available human NSCs (h-NSC) and rat fetal NSCs (rNSCs) were also transduced with BacMam 2.0 GFP. Primary rat neurons and post-differentiated human NSCs were transduced with either BacMam 2.0 GFP or Plasma Membrane-GFP BacMam 2.0 and Synaptophysin-RFP BacMam 2.0 to assess the capability of gene expression in mature neural cell types. Using a GFP marker, we demonstrated that the BacMam virus can consistently transduce neural stem cells with high efficiency and low toxicity. Transduction was also enabled in differentiated NSC, and the expression in primary neurons was dependent on the age of the culture, with preferential labeling of astrocytes in older cultures. BacMam mediated gene delivery provides a superior platform for introducing diverse gene elements, creating assay-ready cells among young neuronal cells and mature astrocytes.