Enhanced osteogenic differentiation potential of Arnica montana and Bellis perennis in C3H10T1/2 multipotent mesenchymal stem cells.

BACKGROUND: Arnica montana and Bellis perennis are two medicinal plants that are thought to accelerate bone repair in homoeopathic literature. Mesenchymal stem cells (MSCs) are multipotent stem cells with the ability to differentiate and regenerate bone or osteogenesis. Hence, we aimed to determine the role of Arnica montana and Bellis perennis on the osteogenic differentiation of the C3H10T1/2 stem cell line. METHODS AND RESULTS: The cell proliferation of Arnica montana and Bellis perennis was evaluated by MTT assay. Osteogenic differentiation of C3H10T1/2 was induced by the addition of ß-glycerophosphate, ascorbic acid and dexamethasone in the differentiation medium over 3 weeks. Cells were treated with Arnica montana and Bellis perennis individually as well as in combination. The osteogenic differentiation potential of Arnica montana and Bellis perennis to differentiate C3H10T1/2 into osteoblasts was measured by alkaline phosphatase activity, alizarin red staining and the expression of Osteocalcin using immunostaining and qRT-PCR. Arnica montana and Bellis perennis could enhance C3H10T1/2 cell proliferation at 1600 µg. Further, the compound showed the ability to augment osteogenesis as confirmed by increased expression of alkaline phosphatase and enhanced calcium accumulation as seen by the Alizarin Red staining and quantification. Enhanced osteogenesis was further supported by the increased expression of osteocalcin in the treated cells with individual and combined doses of Arnica montana and Bellis perennis. Therefore, the findings provide additional support for the positive impact of Arnica montana and Bellis perennis on bone formation. CONCLUSIONS: Our findings suggest that homoeopathic compounds Arnica montana and Bellis perennis can augment osteogenesis individually as well as in combination.

Unlocking the Potential of Obestatin: A Novel Peptide Intervention for Skeletal Muscle Regeneration and Prevention of Atrophy.

Obestatin is derived from the same gene as that of ghrelin and their functions were perceived to be antagonistic. Recent developments have shown that although they are known to have contradictory functions, effect of obestatin on skeletal muscle regeneration is similar to that of ghrelin. Obestatin works through a receptor called GPR39, a ghrelin and motilin family receptor and transduces signals in skeletal muscle similar to that of ghrelin. Not only there is a similarity in the receptor family, but also obestatin targets similar proteins and transcription factors as that of ghrelin (for example, FoxO family members) for salvaging skeletal muscle atrophy. Moreover, like ghrelin, obestatin also works by inducing the transcription of Pax7 which is required for muscle stem cell mobilisation. Hence, there are quite some evidences which points to the fact that obestatin can be purposed as a peptide intervention to prevent skeletal muscle wasting and induce myogenesis. This review elaborates these aspects of obestatin which can be further exploited and addressed to bring obestatin as a clinical intervention towards preventing skeletal muscle atrophy and sarcopenia.

Mitigation of chronic glucotoxicity-mediated skeletal muscle atrophy by arachidonic acid.

Toxicity caused by chronic hyperglycemia is a significant factor affecting skeletal muscle myogenesis, resulting in diabetic myopathy. Chronic and persistent hyperglycemia causes activation of the atrophy-related pathways in the skeletal muscles, which eventually results in inflammation and muscle degeneration. To counteract this process, various bioactive compound has been studied for their reversal or hypertrophic effect. In this study, we explored the molecular mechanisms associated with reversing glucotoxicity's effect in C2C12 cells by arachidonic acid (AA). We found a substantial increase in the pro-inflammatory cytokines and ROS production in hyperglycemic conditions, mitigated by AA supplementation. We found that AA supplementation restored protein synthesis that was downregulated under glucotoxicity conditions. AA enhanced myogenesis by suppressing high glucose induced inflammation and ROS production and enhancing protein synthesis. These results imply that AA has cytoprotective actions against hyperglycemia-induced cytotoxicity.

Arachidonic acid modulates the cellular energetics of human pluripotent stem cells and protects the embryoid bodies from embryotoxicity effects in vitro.

Arachidonic acid (AA), an ω-6 polyunsaturated fatty acid involved in signalling pathways that drive cell fate decisions, has an enhancing role in the immunomodulatory effect on mesenchymal stem cells and the vasculogenesis of embryonic stem cells. 3D embryoid bodies (EBs) from pluripotent stem cells (PSCs) have been used as in vitro models for embryotoxicity for various compounds/drugs. Valproic acid (VA), a common anti-epileptic drug, is known to be embryotoxic and cause malformations in embryos. As early embryogenesis depends on AA, we investigated the embryo protective effects of AA against the embryotoxic drug VA in this study. The effects of AA on the proliferation and cell cycle parameters of PSCs were studied. In particular, the potential of AA to abrogate VA-induced embryotoxicity in vitro was evaluated using ROS detection and antioxidant assays. In response to AA, we observed modulation in cell proliferation of induced pluripotent stem cells (iPSCs) and pluripotent NTERA-2 embryonal carcinoma (EC) cells. The present study substantiates the cytoprotective effects of AA against VA. These results imply that AA plays a critical role in the proliferation and differentiation of iPSCs and EC cells and protects the EBs from cytotoxic damage, thereby ensuring normal embryogenesis. Thus, the bioactive lipid AA may be explored for supplementation to benefit pregnant women treated with long-term anti-epileptic drugs to prevent in-utero fetal growth malformations.

The elusive role of myostatin signaling for muscle regeneration and maintenance of muscle and bone homeostasis.

Skeletal muscle is one of the leading frameworks of the musculo-skeletal system, which works in synergy with the bones. Long skeletal muscles provide stability and mobility to the human body and are primarily composed of proteins. Conversely, improper functioning of various skeletal muscles leads to diseases and disorders, namely, age-related muscle disorder called sarcopenia, a group of genetic muscle disorders such as muscular dystrophies, and severe muscle wasting in cancer known as cachexia. However, skeletal muscle has an excellent ability to undergo hypertrophy and enhanced functioning during sustained exercise over time. Indeed, these processes of skeletal muscle regeneration/hypertrophy, as well as degeneration and atrophy, involve an interplay of various signaling pathways. Myostatin is one such chemokine/myokine with a significant contribution to muscle regeneration or atrophy in multiple conditions. In this review, we try to put together the role and regulation of myostatin as a function of muscle regeneration extrapolated to multiple aspects of its molecular functions.

Significance of Oct-4 transcription factor as a pivotal therapeutic target for CD44+ /24- mammary tumor initiating cells: Aiming at the root of the recurrence.

Breast cancer (BC) remains one of the deadliest and frequently diagnosed metastatic cancers worldwide. Cancer stem cells (CSCs) are the cell population within the tumor niche, having an epithelial to mesenchymal (EMT) transition phenotype, high self-renewal, vigorous metastatic capacity, drug resistance, and tumor relapse. Identification of targets for induction of apoptosis is essential to provide novel therapeutic approaches in BC. Our earlier studies showed that Vitamin C induces apoptotic cell death by losing redox balance in TNBC CSCs. In this study, we have attempted to identify previously unrecognized CSC survival factors that can be used as druggable targets for bCSCs apoptosis regulators isolated from the TNBC line, MDA MB 468. After a thorough literature review, Oct-4 was identified as the most promising marker for its unique abundance in cancer and absence in normal cells and the contribution of Oct-4 to the sustenance of cancer cells. We then validated a very high expression of Oct-4 in the MDA MB 468 bCSCs population using flow-cytometry. The loss of Oct-4 was carried out using small interfering RNA (siRNA)-mediated knockdown in the bCSCs, followed by assessing for cellular apoptosis. Our results indicated that Oct-4 knockdown induced cell death, changes in cellular morphology, inhibited mammosphere formation, and positive for Annexin-V expression, thereby indicating the role of Oct-4 in bCSC survival. Moreover, our findings also suggest the direct interaction between Oct-4 and Vitamin C using in silico docking. This data, hence, contributes towards novel information about Oct-4 highlighting this molecule as a novel survival factor in bCSCs.

Assessment of Threshold Dose of Thoron Inhalation and Its Biological Effects by Mimicking the Radiation Doses in Monazite Placer Deposits Corresponding to the Normal, Medium and Very High Natural Background Radiation Areas.

The dose contributed from thoron (220Rn) and its progeny has been neglected in the dose assessment because of its short half-life (t1/2 = 55.6 s) and generally low concentrations. Recently, concentrations of 220Rn gas and its progeny were found to be pronounced in the traditional residential dwellings in China, on beaches of India and in other countries. Accordingly, we investigated the biological effects of thoron (220Rn) decay products in various mouse organs, succeeding inhalation of thoron gas in BALB/c mouse. We investigated the biological effects upon thoron inhalation on mouse organs with a focus on oxidative stress. These mice were divided into (4 random groups): sham inhalation, thoron inhalation for 1, 4 and 10 days. Various tissues (lung, liver and kidney) were then collected after the time points and subjected to various biochemical analyses. Immediately after inhalation, mouse tissues were excised for gamma spectrometry and 72 h post inhalation for biochemical assays. The gamma spectrometry counts and its subsequent calculation of the equivalent dose showed varied distribution in the lung, liver and kidney. Our results suggest that acute thoron inhalation showed a differential effect on the antioxidant function and exerted pathophysiological alterations via oxidative stress in organs at a higher dose. These findings suggested that thoron inhalation could alter the redox state in organs; however, its characteristics were dependent on the total redox system of the organs as well as the thoron concentration and inhalation time.

The elusive role of myostatin signaling for muscle regeneration and maintenance of muscle and bone homeostasis

Skeletal muscle is one of the leading frameworks of the musculo-skeletal system, which works in synergy with the bones. Long skeletal muscles provide stability and mobility to the human body and are primarily composed of proteins. Conversely, improper functioning of various skeletal muscles leads to diseases and disorders, namely, age-related muscle disorders called sarcopenia, a group of genetic muscle disorders such as muscular dystrophies, and severe muscle wasting in cancer known as cachexia. However, skeletal muscle has an excellent ability to undergo hypertrophy and enhanced functioning during sustained exercise over time. Indeed, these processes of skeletal muscle regeneration/hypertrophy, as well as degeneration and atrophy, involve an interplay of various signaling pathways. Myostatin is one such chemokine/myokine with a significant contribution to muscle regeneration or atrophy in multiple conditions. In this review, we try to put together the role and regulation of myostatin as a function of muscle regeneration extrapolated to multiple aspects of its molecular functions.

Sodium fluoride induces skeletal muscle atrophy via changes in mitochondrial and sarcomeric proteomes.

Sodium Fluoride (NaF) can change the expression of skeletal muscle proteins. Since skeletal muscle is rich in mitochondrial and contractile (sarcomeric) proteins, these proteins are sensitive to the effects of NaF, and the changes are dose-and time-dependent. In the current study, we have analysed the effect of high concentrations of NaF (80ppm) on mouse skeletal muscle at two different time points, i.e., 15 days and 60 days. At the end of the experimental time, the animals were sacrificed, skeletal muscles were isolated, and proteins were extracted and subjected to bioinformatic (Mass Spectrometric) analysis. The results were analysed based on changes in different mitochondrial complexes, contractile (sarcomeric) proteins, 26S proteasome, and ubiquitin-proteasome pathway. The results showed that the mitochondrial proteins of complex I, II, III, IV and V were differentially regulated in the groups treated with 80ppm of NaF for 15 days and 60 days. The network analysis indicated more changes in mitochondrial proteins in the group treated with the higher dose for 15 days rather than 60 days. Furthermore, differential expression of (sarcomeric) proteins, downregulation of 26S proteasome subunits, and differential expression in proteins related to the ubiquitin-proteasome pathway lead to muscle atrophy. The differential expression might be due to the adaptative mechanism to counteract the deleterious effects of NaF on energy metabolism. Data are available via ProteomeXchange with identifier PXD035014.

Fucoidan-Incorporated Composite Scaffold Stimulates Osteogenic Differentiation of Mesenchymal Stem Cells for Bone Tissue Engineering.

Globally, millions of bone graft procedures are being performed by clinicians annually to treat the rising prevalence of bone defects. Here, the study designed a fucoidan from Sargassum ilicifolium incorporated in an osteo-inductive scaffold comprising calcium crosslinked sodium alginate-nano hydroxyapatite-nano graphene oxide (Alg-HA-GO-F), which tends to serve as a bone graft substitute. The physiochemical characterization that includes FT-IR, XRD, and TGA confirms the structural integration between the materials. The SEM and AFM reveal highly suitable surface properties, such as porosity and nanoscale roughness. The incorporation of GO enhanced the mechanical strength of the Alg-HA-GO-F. The findings demonstrate the slower degradation and improved protein adsorption in the fucoidan-loaded scaffolds. The slow and sustained release of fucoidan in PBS for 120 h provides the developed system with an added advantage. The apatite formation ability of Alg-HA-GO-F in the SBF solution predicts the scaffold's osteointegration and bone-bonding capability. In vitro studies using C3H10T1/2 revealed a 1.5X times greater cell proliferation in the fucoidan-loaded scaffold than in the control. Further, the results determined the augmented alkaline phosphatase and mineralization activity. The physical, structural, and enriching osteogenic potential results of Alg-HA-GO-F indicate that it can be a potential bone graft substitute for orthopedic applications.

Thorium promotes lung, liver and kidney damage in BALB/c mouse via alterations in antioxidant systems.

Thorium (232Th), long lived (14.05 billion years) most stable thorium isotope, is thrice naturally abundant than uranium. 232Th occurs as rocky deposits and black monazite sands on the earth's crust geographically distributed in coastal South India and other places globally. Monazite sand comprises of cerium and large quantities of radioactive thorium. The environmental hazard lies in monazite rich area being termed as High Background Radiation Area (HBRA). In this study, we mimicked the HBRA under controlled chamber conditions using thorium oxalate as a thorium source for BALB/c mice exposure. Furthermore, sequential radio-disintegration of 232 Th leads to thoron (220Rn), the noble gas and other daughter products/progeny predominantly via alpha decay/emissions. Such progeny tend to attach to aerosol and dust particles having potential inhalation hazard followed by alpha emissions and damages that we evaluated in mouse lung tissues post thoron inhalation. Secondly, along with the radio disintegration and alpha emission, high energy gamma is also generated that can travel to various distant organs through the systemic circulation, as significant findings of our study as damages to the liver and kidney. The mechanistic findings include the damages to the hematological, immunological and cellular antioxidant systems along with activation of canonical NF-κß pathway via double stranded DNA damage.

Burden of osteoarthritis in India and its states, 1990-2019: findings from the Global Burden of disease study 2019.

OBJECTIVE: To describe the burden of osteoarthritis (OA) in India from 1990 to 2019. DESIGN: Data from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were used. The burden of OA -knee OA, hip OA, hand OA, and other OA- was estimated for India and its states from 1990 to 2019 through a systematic analysis of prevalence, incidence, years lived with disability (YLD), and disability-adjusted life years (DALY) using methods reported in GBD 2019 study. RESULT: Around 23.46 million individuals in India had OA in 1990; this increased to 62.35 million in 2019. The age-standardised prevalence of OA increased from 4,895 (95% uncertainty interval (UI):4,420-5,447) in 1990-5313 (95%UI:4,799-5,898) in 2019, per 100,000 persons. Similarly, DALYs due to OA increased from 0.79 million (95%UI:0.40-1.55) to 2.12 million (95%UI:1.07-4.23); while age-standardised DALYs increased from 164 (95%UI:83-325) to 180 (95%UI:91-361) per 100,000 persons from 1990 to 2019. OA was the 20th most common cause of YLDs in India in 2019, accounting for 1.48% (95%UI:0.88-2.78) of all YLDs; increasing from 23rd most common cause in 1990 (1.25%(95%UI:0.74-2.34)). Knee OA was the most common form of OA, followed by hand OA. The prevalence, incidence, and DALYs for OA and knee OA were consistently higher in females than males. CONCLUSION: The burden and impact of OA in India are substantial and is increasing. Adopting suitable control and preventive community measures to reduce modifiable risk factors (obesity, injuries, occupational stress) are needed to reduce the current and future burden of OA in India.

High concentration of sodium fluoride in drinking water induce hypertrophy versus atrophy in mouse skeletal muscle via modulation of sarcomeric proteins.

Fluoride at high doses is a well-known toxic agent for the musculoskeletal system, primarily in bone and cartilage cells. Research on fluoride toxicity concerning particularly on the skeletal muscle is scanty. We hypothesized that during skeletal fluorosis, along with bone, muscle is also affected, so we have evaluated the effects of Sodium fluoride (NaF) on mouse skeletal muscles. Sodium fluoride (80 ppm) was administered to 5-week-old C57BL6 mice drinking water for 15 and 60 days, respectively. We carried out histology, primary culture, molecular and proteomic analysis of fluoride administered mouse skeletal muscles. Results indicated an increase in the muscle mass (hypertrophy) in vivo and myotubes ex vivo by activating the IGF1/PI3/Akt/mTOR signalling pathway due to short term NaF exposure. The long-term exposure of mice to NaF caused loss of muscle proteins leading to muscle atrophy due to activation of the ubiquitin-proteasome pathway. Differentially expressed proteins were characterized and mapped using a proteomic approach. Moreover, the factors responsible for protein synthesis and PI3/Akt/mTOR pathway were upregulated, leading to muscle hypertrophy during the short term NaF exposure. Long term exposure to NaF resulted in down-regulation of metabolic pathways. Elevated myostatin resulted in the up-regulation of the muscle-specific E3 ligases-MuRF1, promoting the ubiquitination and proteasome-mediated degradation of critical sarcomeric proteins.

Recycled mesoporous magnetic composites with high surface area derived from plastic and de-oiled sludge wastes: An empirical comparison on their competitive performance for toxic Cr (VI) removal.

The current study focused on the comparative removal of hexavalent chromium using two magnetically modified hybrid adsorbent composites. Their precursor chars were prepared from bio sludge and plastic waste derivatives. The coating of magnetite on the chars' surface was evident from the SEM micrographs. Infusion of magnetite nanoparticles in the native chars aided in the reduction of the composite particles' sizes, thus, forming high surface area composites. Screening of uptake capacities among various blends of char and magnetite were surveyed. Composites of both kinds with a 1:5 ratio of char: iron salts composition answered well. The pHZPC and zeta potential values of the composites indicated the neutral charge on the composites' surface. This suggested the need for a highly acidic environment for efficient Cr(VI) removal. Optimum economic conditions for Cr(VI) removal were obtained from the batch studies (solution pH - 1.5; contact time - (a) MPC [magnetic plastic char] - 60 min (b) MBC [magnetic biochar] - 40 min; temperature - 25 °C). The maximum monolayer adsorption capacity of MPC and MBC were found to be 84.67 mg/g and 53.83 mg/g respectively. Isotherm, kinetic and thermodynamic studies revealed the adsorption systems' inclination towards physisorption. From the characterization and modeling results, electrostatic force of attraction and pore filling was anticipated to be the mechanism of adsorption for both MPC and MBC. Thus, in the relative removal studies, MBC was found to compete better than MPC due to its enhanced porosity and surface area.

Cell therapy research for Diabetes: Pancreatic ß cell differentiation from pluripotent stem cells.

Human pluripotent stem cells (PSCs), both embryonic and induced pluripotent stem cells (iPSCs), have been differentiated into pancreatic ß isletsin vitrofor more than a decade. The idea is to get enough ß cells for cell transplantation for diabetics. Finding a standard cell therapy for diabetes is essential because of the logarithmic increase in the global population of people with diabetes and the insufficient availability of the human cadaveric pancreas. Moreover, with better insights into developmental biology, thein vitroß cell differentiation protocols have depended on thein vivoß cell organogenesis. Various protocols for pancreatic ß cell differentiation have been developed. Such protocols are based on the modulation of cell signalling pathways with growth factors, small molecules, RNAi approaches, directed differentiation using transcription factors, genome editing. Growth factor free differentiation protocols, epigenetic modulations, 3D differentiation approaches, and encapsulation strategies have also been reported for better glycemic control and endocrine modulations. Here, we have reviewed various aforementionedin vitroß cell differentiation protocols from human PSCs, their respective comparisons, challenges, past, present, and future. The literature has been reviewed primarily from PubMed from the year 2000 till date using the mentioned keywords.

Recent advances in cellular effects of fluoride: an update on its signalling pathway and targeted therapeutic approaches.

Fluoride is a natural element essential in minute quantities in human's to maintain dental and skeletal health. However, the disease fluorosis manifests itself due to excessive fluoride intake mostly through drinking water and sometimes through food. At the cellular energetics level, fluoride is a known inhibitor of glycolysis. At the tissue level, the effect of fluoride has been more pronounced in the musculoskeletal systems due to its ability to retain fluoride. Fluoride alters dentinogenesis, thereby affecting the tooth enamel formation. In bones, fluoride alters the osteogenesis by replacing calcium, thus resulting in bone deformities. In skeletal muscles, high concentration and long term exposure to fluoride causes loss of muscle proteins leading to atrophy. Although fluorosis is quite a familiar problem, the exact molecular pathway is not yet clear. Extensive research on the effects of fluoride on various organs and its toxicity was reported. Indeed, it is clear that high and chronic exposure to fluoride causes cellular apoptosis. Accordingly, in this review, we have highlighted fluoride-mediated apoptosis via two vital pathways, mitochondrial-mediated and endoplasmic reticulum stress pathways. This review also elaborates on new cellular energetic, apoptotic pathways and therapeutic strategies targeted to treat fluorosis.

Sca1+ Progenitor Cells (Ex vivo) Exhibits Differential Proteomic Signatures From the Culture Adapted Sca1+ Cells (In vitro), Both Isolated From Murine Skeletal Muscle Tissue.

Stem cell antigen-1 (Sca-1) is a glycosyl-phosphatidylinositol-anchored membrane protein that is expressed in a sub-population of muscle stem and progenitor cell types. Reportedly, Sca-1 regulates the myogenic property of myoblasts and Sca-1-/- mice exhibited defective muscle regeneration. Although the role of Sca-1 in muscle development and maintenance is well-acknowledged, molecular composition of muscle derived Sca-1+ cells is not characterized. Here, we applied a high-resolution mass spectrometry-based workflow to characterize the proteomic landscape of mouse hindlimb skeletal muscle derived Sca-1+ cells. Furthermore, we characterized the impact of the cellular microenvironments on the proteomes of Sca-1+ cells. The proteome component of freshly isolated Sca-1+ cells (ex vivo) was compared with that of Sca-1+ cells expanded in cell culture (in vitro). The analysis revealed significant differences in the protein abundances in the two conditions reflective of their functional variations. The identified proteins were enriched in various biological pathways. Notably, we identified proteins related to myotube differentiation, myotube cell development and myoblast fusion. We also identified a panel of cell surface marker proteins that can be leveraged in future to enrich Sca-1+ cells using combinatorial strategies. Comparative analysis implicated the activation of various pathways leading to increased protein synthesis under in vitro condition. We report here the most comprehensive proteome map of Sca-1+ cells that provides insights into the molecular networks operative in Sca-1+ cells. Importantly, through our work we generated the proteomic blueprint of protein abundances significantly altered in Sca-1+ cells under ex vivo and in vitro conditions. The curated data can also be visualized at https://yenepoya.res.in/database/Sca-1-Proteomics .

Differential sensitivities of triple-negative breast cancer stem cell towards various doses of vitamin C: An insight into the internal antioxidant systems.

Cancer stem cells (CSCs) are quiescent and self-renewing, having low levels of reactive oxygen species (ROS), and are responsible for cancer recurrence after chemotherapy and radiotherapy. However, the interplay between the ROS production and scavenging from the oxidative stress has never been studied in breast CSCs. In this present study, we have investigated the cellular energetics of two triple-negative breast cancer stem cells (MDA-MB-231 and MDA-MB-468) treated with two pharmacological doses of vitamin C (10 and 20 mM) that generated ROS. Our results indicate a differential behavior of ROS scavenging by both the CSCs. MDA-MB-468 CSCs exhibited higher resistance to ROS induced damage owing to the higher antioxidant activity, lower mitochondrial damage, and less decrease in membrane potential (ΔΨm ) as compared with MDA-MB-231 CSCs. Moreover, MDA-MB-231 CSCs exhibited an intrinsic apoptosis pathway by activating the cytochrome c, caspase-9, 3, 7, and cleaved PARP upon treatment with vitamin C. This data suggests a possible strategy for targeting breast CSCs using vitamin C. Taken together, the CSCs from MDA-MB-231 could be easily targeted by high/pharmacological doses of vitamin C (≥20 mM) thereby indicating a less robust internal antioxidant machinery.

Lung damage by thoron progenies versus possible damage redemption by lung stem cells: a perspective.

PURPOSE: Natural radiation is the major source of human exposure to ionizing radiation. About 52% of the total dose received from the high natural background radiations (HNBR) areas are due to inhalation dose from radon (222Rn)/thoron (220Rn) and their progenies. Hence, we reviewed the biological effects of 222Rn/220Rn and their progenies on lung tissue, and the possible role of lung stem cells in salvaging the damage caused by 222Rn/220Rn and their progenies. MATERIALS AND METHOD: We have extensively reviewed articles among several hits obtained in PubMed, Scopus, and Elsevier databases with keywords 'Radon/Thoron' OR Thoron progeny/Radon progeny OR 'Thoron/Radon inhalation and lungs', and proceed for further analysis. Also, databases related to oxidative damage to lung stem cells by radiation and the repair mechanisms involved by the lung stem cells were also included. RESULTS: Based on the existing epidemiological data on radon in residential buildings, we found that evidence exists on the association of radon induced lung carcinogenesis, but the data regarding the role of thoron induced lung damage is very limited and inconclusive. We also found that limited information has been provided based on ecological designs, leading to poor documentation of health statistics, in particular, organ-specific cancer rates. Finally, we tried to elucidate the possible mechanisms of lung injury induced by thoron inhalation and the probable role of lung stem cell toward the redemption of such oxidative damages. CONCLUSION: Existing epidemiological data on thoron inhalation and associated health outcomes are limited and inconclusive. Further, in vivo experiments, with respect to radon/thoron inhalation dose rate ranges corresponding to the HNBR areas will be helpful in understanding the cellular and molecular effects.