Leber's hereditary optic neuropathy: Current approaches and future perspectives on Mesenchymal stem cell-mediated rescue.

Leber's Hereditary Optic Neuropathy (LHON) is an inherited optic nerve disorder. It is a mitochondrially inherited disease due to point mutation in the MT-ND1, MT-ND4, and MT-ND6 genes of mitochondrial DNA (mtDNA) coding for complex I subunit proteins. These mutations affect the assembly of the mitochondrial complex I and hence the electron transport chain leading to mitochondrial dysfunction and oxidative damage. Optic nerve cells like retinal ganglion cells (RGCs) are more sensitive to mitochondrial loss and oxidative damage which results in the progressive degeneration of RGCs at the axonal region of the optic nerve leading to bilateral vision loss. Currently, gene therapy using Adeno-associated viral vector (AAV) is widely studied for the therapeutics application in LHON. Our review highlights the application of cell-based therapy for LHON. Mesenchymal stem cells (MSCs) are known to rescue cells from the pre-apoptotic stage by transferring healthy mitochondria through tunneling nanotubes (TNT) for cellular oxidative function. Empowering the transfer of healthy mitochondria using MSCs may replace the mitochondria with pathogenic mutation and possibly benefit the cells from progressive damage. This review discusses the ongoing research in LHON and mitochondrial transfer mechanisms to explore its scope in inherited optic neuropathy.

COVID-19 and olfactory dysfunction: A possible associative approach towards neurodegenerative diseases.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent of novel coronavirus 2019 (COVID-19), has kept the globe in disquiets due to its severe life-threatening conditions. The most common symptoms of COVID-19 are fever, sore throat, and shortness of breath. According to the anecdotal reports from the health care workers, it has been suggested that the virus could reach the brain and can cause anosmia, hyposmia, hypogeusia, and hypopsia. Once the SARS-CoV-2 has entered the central nervous system (CNS), it can either exit in an inactive form in the tissues or may lead to neuroinflammation. Here, we aim to discuss the chronic infection of the olfactory bulb region of the brain by SARS-CoV-2 and how this could affect the nearby residing neurons in the host. We further review the probable cellular mechanism and activation of the microglia 1 phenotype possibly leading to various neurodegenerative disorders. In conclusion, SARS-CoV-2 might probably infect the olfactory bulb neuron enervating the nasal epithelium accessing the CNS and might cause neurodegenerative diseases in the future.

Does retina play a role in Parkinson's Disease?

Visual disorder is one of the non-motor symptoms found in Parkinson's disease (PD). It can be easily identified in the early stages even before the spread of pathological conditions to the brain parts. Studies have revealed that loss of dopamine (DA) cells in retinal layers is a prime cause for both retinal disturbance and pathological conditions of PD. This reduction of DA in retina is due to the aggregation of phosphorylated α-synuclein (aSyn) in the intra-retinal region, which eventually results in visual impairment in PD. Until now, very limited studies have been focused on the mechanism of aSyn influence and DA depletion as a cause for both retinal layer dysfunction and PD. Thus, more research is warranted to provide the missing connection between the exact role of DA and aSyn as a risk factor for visual problems in PD. Hence, the current review's focus is on the function and effects of DA degeneration in retinal cells of PD. Further, we suggest that iron plays a major role in regulating the aggregation of aSyn in the DA cells of retina and brain in PD. The study finds that the unidentified pathophysiological role of retinal degeneration in PD is an essential biomarker that needs further investigation to use it as a novel therapy in treating retinal dysfunctions in PD.

Analysis of genetic damage and gene polymorphism in hepatocellular carcinoma (HCC) patients in a South Indian population.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second leading cause of cancer death in many regions of Asia and the etiology of human HCC is clearly multi-factorial. The development of effective markers for the detection of HCC could have an impact on cancer mortality and significant health implications worldwide. The subjects presented here were recruited based on the serum alpha-fetoprotein level, which is an effective marker for HCC. Further, the chromosomal alterations were elucidated using trypsin G-banding. HCCs with p53 mutations have high malignant potential and are used as an indicator for the biological behavior of recurrent HCCs. The functional polymorphism in the XRCC1 gene, which participates in the base-excision repair of oxidative DNA damage, was associated with increased risk of early onset HCC. Thus, in this investigation, the p53 and XRCC1 gene polymorphisms using the standard protocols were also assessed to find out whether these genes may be associated with HCC susceptibility. METHODS: Blood samples from HCC patients (n = 93) were collected from oncology clinics in South India. Control subjects (n = 93) who had no history of tumors were selected and they were matched to cases on sex, age, and race. Peripheral blood was analyzed for chromosomal aberrations (CAs) and micronuclei (MN) formation. p53 and XRCC1 genotypes were detected using a PCR-RFLP technique. RESULTS: Specific biomarkers on cytogenetic endpoints might help in diagnosis and treatment measures. The frequencies of genotypes between groups were calculated by χ(2) test. A statistically significant (p < 0.05) increase in CA was observed in HCC patients compared to their controls as confirmed by ANOVA and MN shows insignificant results. The study on p53 Arg72Pro and XRCC1 Arg399Gln polymorphism in HCC patients demonstrated differences in allele frequencies compared to their controls. CONCLUSIONS: The present study indicates that chromosomal alterations and the genetic variations of p53 and XRCC1 may contribute to inter-individual susceptibility to HCC. A very limited role of genetic polymorphism was investigated in modulating the HCC risk, but the combined effect of these variants may interact to increase the risk of HCC in the South Indian population.

Assessment of occupational cytogenetic risk, among petrol station workers.

The focal aim of this study was to assess the frequency of chromosomal aberrations (CA) including chromatid type aberrations (CTA) and chromosomal type aberrations (CSA), micronucleus (MN) and XRCC1 399 Arg/Gln polymorphism in the peripheral blood lymphocytes of 27 petrol pump workers and same number of controls to explore the possible cytogenetic risk on occupational exposure to petrol vapors. The exposed subjects and controls were classified into two groups based on their age (group I < 40 years; group II > 40 years) apart from the classification of the exposed subjects based on their exposure duration (> 8 and < 8 years). CTA and MN frequency were significantly higher in petrol pump workers (p < 0.05) with longer work duration. CTA was found to increase with age in the exposed subjects as well as controls, with exposed subjects showing a statistically higher degree. This effect was not observed in MN. A significantly higher frequency of MN was observed in the smoking petrol pump workers than in control smokers (p < 0.05). No association was found between smoking and CA in both subjects. The study on XRCC1 399 Arg/gln polymorphism in petrol pump workers demonstrated very less difference in allele frequency compared to controls. In conclusion, these datas indicate that petrol pump workers under risk group should be monitored for any long-term adverse effects of the exposure.

Evaluation of the genetic alterations in direct and indirect exposures of hexavalent chromium [Cr(VI)] in leather tanning industry workers North Arcot District, South India.

PURPOSE: The focal aim of the present study was to identify the genetic alterations occurring in the tannery workers and surrounding inhabitants chronically exposed to hexavalent chromium [Cr(VI)]. METHODS: A total of 108 samples which includes 72 exposed subjects [36 directly exposed (DE) subjects and 36 indirectly exposed (IE) subjects] and 36 controls were recruited for this study. The exposed subjects and controls were selected based on the Cr level present in air and their urine. Directly exposed subjects were categorized based on their work duration in the tannery industries, whereas the indirectly exposed subjects were categorized based on their year of residence in the place adjacent to tannery industries for more than 3 decades. Controls were normal and healthy. Age was matched for the exposed subjects and controls. The exposed subjects as well as the controls were categorized based on their age (group I, <40 years; group II, >41 years). Cell cultures were established from blood samples (5 ml from each subject) collected from the subjects (exposed subjects and controls) after obtaining informed consent. G-banding (Giemsa staining) of the cultures, micronucleus (MN) assay and comet assay were used to identify the genetic alterations of individuals exposed to Cr(VI) in comparison with the controls. RESULTS: A higher degree of total CA [12 ± 8.49 (21-25 years)] and MN [18.69 ± 7.39 (11-15 years)] was found in DE subjects compared to other groups. In IE subjects, elevated levels of CA [5.67 ± 1.15 (51-60 years)] and MN [25 ± 9.89 (71-80 years)] were observed. As expected, controls exhibited minimal number of alterations. The overall CA frequency due to Cr exposure was significantly different from that of the controls for both chromatid and chromosome type aberrations (P < 0.05 by ANOVA). The MN/1,000 binucleated cells were significantly increased (P < 0.05) in the peripheral lymphocytes of DE and IE subjects in comparison with controls. The mean tail length of comet assay for DE, IE and controls were analyzed. The mean tail length of DE subjects [4.21 (3.21-10.98)] was higher compared to that of IE subjects [3.98 (2.98-11.27)] and controls [3.01 (2.68-9.40)]. CONCLUSION: In conclusion, this work shows a clear genotoxic effect associated with chromium exposure, both directly and indirectly. Our result reinforces the higher sensitivity of cytogenetic assays for the biomonitoring of occupationally exposed populations. There is a strong need to educate those who work with potentially hazardous heavy about its adverse effects and highlight the importance of using protective measures.

Identification of Chromosomal Aberrations by Using Trypsin G-banding in Hepatocellular Carcinoma Patients (HCC) in Tamil Nadu, India.

Hepatocellular carcinoma (HCC) (or liver cancer) is one of the most common human malignancies worldwide. Aetiologically, HCC is closely associated with chronic hepatitis B and C virus infection, cirrhosis and alcohol intake. The objective of the present study was to elucidate the chromosomal abberations (CA) in HCC patients using the trypsin G-banding technique. This study may help in understanding the pattern of the disease and to assess whether these aberrations are associated with HCC susceptibility. The study examined 51 HCC cases and an equal number (n = 51) of age and gender matched cancer-free controls recruited from the hospitals in Tamil Nadu. The HCC cases were grouped depending upon their age into group I (≤ 45 years) and group II (≥ 46 years). The development of effective markers for the detection of HCC could have an impact on cancer mortality and may have significant public health implications worldwide. Subjects were recruited based on their alpha-fetoprotein (AFP) serum level, which is an effective marker for HCC. In the HCC cases, a higher number of chromatid aberrations [group I 13(25.5%) and group II 43(84.3%)] and CA [group I 10(19.6%) and group II 28(54.9%)] were observed. In contrast, controls showed a lower number of chromatid [group I 5(9.8%) and group II 12(23.5%)] and CA [group I 4(7.8%) and group II 9(17.6%)]. In conclusion, the results of this study contribute to the validation of CA as an intermediate end point in carcinogenesis. Because many people are unaware of this lethal disease, this study will raise awareness of this cancer.