Advances in an In Vitro Tuberculosis Infection Model Using Human Lung Organoids for Host-Directed Therapies.

The emergence of drug-resistant Mycobacterium tuberculosis (M.tb) has led to the development of novel anti-tuberculosis (anti-TB) drugs. Common methods for testing the efficacy of new drugs, including two-dimensional cell culture models or animal models, have several limitations. Therefore, an appropriate model representative of the human organism is required. Here, we developed an M.tb infection model using human lung organoids (hLOs) and demonstrated that M.tb H37Rv can infect lung epithelial cells and human macrophages (hMφs) in hLOs. This novel M.tb infection model can be cultured long-term and split several times while maintaining a similar number of M.tb H37Rv inside the hLOs. Anti-TB drugs reduced the intracellular survival of M.tb in hLOs. Notably, M.tb growth in hLOs was effectively suppressed at each passage by rifampicin and bedaquiline. Furthermore, a reduction in inflammatory cytokine production and intracellular survival of M.tb were observed upon knockdown of MFN2 and HERPUD1 (host-directed therapeutic targets for TB) in our M.tb H37Rv-infected hLO model. Thus, the incorporation of hMφs and M.tb into hLOs provides a powerful strategy for generating an M.tb infection model. This model can effectively reflect host-pathogen interactions and be utilized to test the efficacy of anti-TB drugs and host-directed therapies.

Elucidating the Role of Reduction Kinetics in the Phase-Controlled Growth on Preformed Nanocrystal Seeds: A Case Study of Ru.

This study demonstrates the crucial role of reduction kinetics in phase-controlled synthesis of noble-metal nanocrystals using Ru nanocrystals as a case study. We found that the reduction kinetics played a more important role than the templating effect from the preformed seed in dictating the crystal structure of the deposited overlayers despite their intertwined effects on successful epitaxial growth. By employing two different polyols, a series of Ru nanocrystals with tunable sizes of 3-7 nm and distinct patterns of crystal phase were synthesized by incorporating different types of Ru seeds. Notably, the use of ethylene glycol and triethylene glycol consistently resulted in the formation of Ru shell in natural hexagonal close-packed (hcp) and metastable face-centered cubic (fcc) phases, respectively, regardless of the size and phase of the seed. Quantitative measurements and theoretical calculations suggested that this trend was a manifestation of the different reduction kinetics associated with the precursor and the chosen polyol, which, in turn, affected the reduction pathway (solution versus surface) and packing sequence of the deposited Ru atoms. This work not only underscores the essential role of reduction kinetics in controlling the packing of atoms and thus the phase taken by Ru nanocrystals but also suggests a potential extension to other noble-metal systems.

RBFOX2-regulated TEAD1 alternative splicing plays a pivotal role in Hippo-YAP signaling.

Alternative pre-mRNA splicing is key to proteome diversity; however, the biological roles of alternative splicing (AS) in signaling pathways remain elusive. Here, we focus on TEA domain transcription factor 1 (TEAD1), a YAP binding factor in the Hippo signaling pathway. Public database analyses showed that expression of YAP-TEAD target genes negatively correlated with the expression of a TEAD1 isoform lacking exon 6 (TEAD1ΔE6) but did not correlate with overall TEAD1 expression. We confirmed that the transcriptional activity and oncogenic properties of the full-length TEAD1 isoform were greater than those of TEAD1ΔE6, with the difference in transcription related to YAP interaction. Furthermore, we showed that RNA-binding Fox-1 homolog 2 (RBFOX2) promoted the inclusion of TEAD1 exon 6 via binding to the conserved GCAUG element in the downstream intron. These results suggest a regulatory mechanism of RBFOX2-mediated TEAD1 AS and provide insight into AS-specific modulation of signaling pathways.

A novel G3BP1-GFP reporter human lung cell system enabling real-time monitoring of stress granule dynamics for in vitro lung toxicity assessment.

Under various cellular stress conditions, including exposure to toxic chemicals, RNA-binding proteins (RBPs), including Ras GTPase-activating protein-binding protein 1 (G3BP1), aggregate and form stress granule complexes, which serve as hallmarks of cellular stress. The existing methods for analyzing stress granule assembly have limitations in the rapid detection of dynamic cellular stress and ignore the effects of constitutively overexpressed RBP on cellular stress and stress-related processes. Therefore, to overcome these limitations, we established a G3BP1-GFP reporter in a human lung epithelial cell line using CRISPR/Cas9-based knock-in as an alternative system for stress granule analysis. We showed that the G3BP1-GFP reporter system responds to stress conditions and forms a stress granule complex similar to that of native G3BP1. Furthermore, we validated the stress granule response of an established cell line under exposure to various household chemicals. Overall, this novel G3BP1-GFP reporter human lung cell system is capable of monitoring stress granule dynamics in real time and can be used for assessing the lung toxicity of various substances in vitro.

Mangiferin, a component of Mangifera indica leaf extracts, inhibits lipid synthesis in human sebocytes.

Inhibition of lipid synthesis in sebocytes is essential for acne treatments. The effects of natural product-derived substances on lipid synthesis are unknown. This study investigated the effects of water extract of Mangifera indica leaves (WEML) on lipid synthesis in human sebocytes. Sebocyte differentiation in low serum conditions increased lipid accumulation and proliferator-activated receptor γ expression. WEML treatment significantly inhibited lipid accumulation and adipogenic mRNA expression in sebocytes. Mangiferin, a bioactive compound in WEML, also reduced lipid accumulation and adipogenic mRNA expression via the AKT pathway. Thus, WEML and mangiferin effectively inhibit lipid synthesis in sebocytes, showing promise for acne treatment.

The role of alternative pre-mRNA splicing in cancer progression.

Alternative pre-mRNA splicing is a critical mechanism that generates multiple mRNA from a single gene, thereby increasing the diversity of the proteome. Recent research has highlighted the significance of specific splicing isoforms in cellular processes, particularly in regulating cell numbers. In this review, we examine the current understanding of the role of alternative splicing in controlling cancer cell growth and discuss specific splicing factors and isoforms and their molecular mechanisms in cancer progression. These isoforms have been found to intricately control signaling pathways crucial for cell cycle progression, proliferation, and apoptosis. Furthermore, studies have elucidated the characteristics and functional importance of splicing factors that influence cell numbers. Abnormal expression of oncogenic splicing isoforms and splicing factors, as well as disruptions in splicing caused by genetic mutations, have been implicated in the development and progression of tumors. Collectively, these findings provide valuable insights into the complex interplay between alternative splicing and cell proliferation, thereby suggesting the potential of alternative splicing as a therapeutic target for cancer.

Octyl syringate is preferentially cytotoxic to cancer cells via lysosomal membrane permeabilization and autophagic flux inhibition.

The autophagy-mediated lysosomal pathway plays an important role in conferring stress tolerance to tumor cells during cellular stress such as increased metabolic demands. Thus, targeted disruption of this function and inducing lysosomal cell death have been proved to be a useful cancer therapeutic approach. In this study, we reported that octyl syringate (OS), a novel phenolic derivate, was preferentially cytotoxic to various cancer cells but was significantly less cytotoxic to non-transformed cells. Treatment with OS resulted in non-apoptotic cell death in a caspase-independent manner. Notably, OS not only enhanced accumulation of autophagic substrates, including lapidated LC3 and sequestosome-1, but also inhibited their degradation via an autophagic flux. In addition, OS destabilized the lysosomal function, followed by the intracellular accumulation of the non-digestive autophagic substrates such as bovine serum albumin and stress granules. Furthermore, OS triggered the release of lysosomal enzymes into the cytoplasm that contributed to OS-induced non-apoptotic cell death. Finally, we demonstrated that OS was well tolerated and reduced tumor growth in mouse xenograft models. Taken together, our study identifies OS as a novel anticancer agent that induces lysosomal destabilization and subsequently inhibits autophagic flux and further supports development of OS as a lysosome-targeting compound in cancer therapy. • Octyl syringate, a phenolic derivate, is preferentially cytotoxic to various cancer cells. • Octyl syringate destabilizes the lysosomal function. • Octyl syringate blocks the autophagic flux. • Octyl syringate is a potential candidate compound for cancer therapy.

Local data commons: the sleeping beauty in the community of data commons.

BACKGROUND: Public Data Commons (PDC) have been highlighted in the scientific literature for their capacity to collect and harmonize big data. On the other hand, local data commons (LDC), located within an institution or organization, have been underrepresented in the scientific literature, even though they are a critical part of research infrastructure. Being closest to the sources of data, LDCs provide the ability to collect and maintain the most up-to-date, high-quality data within an organization, closest to the sources of the data. As a data provider, LDCs have many challenges in both collecting and standardizing data, moreover, as a consumer of PDC, they face problems of data harmonization stemming from the monolithic harmonization pipeline designs commonly adapted by many PDCs. Unfortunately, existing guidelines and resources for building and maintaining data commons exclusively focus on PDC and provide very little information on LDC. RESULTS: This article focuses on four important observations. First, there are three different types of LDC service models that are defined based on their roles and requirements. These can be used as guidelines for building new LDC or enhancing the services of existing LDC. Second, the seven core services of LDC are discussed, including cohort identification and facilitation of genomic sequencing, the management of molecular reports and associated infrastructure, quality control, data harmonization, data integration, data sharing, and data access control. Third, instead of commonly developed monolithic systems, we propose a new data sharing method for data harmonization that combines both divide-and-conquer and bottom-up approaches. Finally, an end-to-end LDC implementation is introduced with real-world examples. CONCLUSIONS: Although LDCs are an optimal place to identify and address data quality issues, they have traditionally been relegated to the role of passive data provider for much larger PDC. Indeed, many LDCs limit their functions to only conducting routine data storage and transmission tasks due to a lack of information on how to design, develop, and improve their services using limited resources. We hope that this work will be the first small step in raising awareness among the LDCs of their expanded utility and to publicize to a wider audience the importance of LDC.

Cyclophilin A is an endogenous ligand for the triggering receptor expressed on myeloid cells-2 (TREM2).

Triggering receptor expressed on myeloid cells 2 (TREM2) is a cell surface receptor expressed on macrophages, microglial cells, and pre-osteoclasts, and that participates in diverse cellular function, including inflammation, bone homeostasis, neurological development, and coagulation. In spite of the indispensable role of the TREM2 protein in the maintenance of immune homeostasis and osteoclast differentiation, the exact ligand for TREM2 has not yet been identified. Here, we report a putative TREM2 ligand which is secreted from MC38 cells and identified as a cyclophilin A (CypA). A specific interaction between CypA and TREM2 was shown at both protein and cellular levels. Exogenous CypA specifically interacted and co-localized with TREM2 in RAW264.7 cells, and the physical interactions were shown to regulate TREM2 signaling transduction. The Pro144 residue in the extracellular domain of TREM2 was found to be the specific binding site of CypA. When considered together, this provides evidence that CypA interacts specifically with TREM2 as a potent ligand.

Pulmonary fibrosis model using micro-CT analyzable human PSC-derived alveolar organoids containing alveolar macrophage-like cells.

Human lung organoids (hLOs) are useful for disease modelling and drug screening. However, a lack of immune cells in hLOs limits the recapitulation of in vivo cellular physiology. Here, we generated hLOs containing alveolar macrophage (AMφ)-like cells derived from pluripotent stem cells (PSC). To bridge hLOs with advanced human lung high-resolution X-ray computed tomography (CT), we acquired quantitative micro-CT images. Three hLO types were observed during differentiation. Among them, alveolar hLOs highly expressed not only lung epithelial cell markers but also AMφ-specific markers. Furthermore, CD68+ AMφ-like cells were spatially organized on the luminal epithelial surface of alveolar hLOs. Bleomycin-treated alveolar hLOs showed upregulated expression of fibrosis-related markers and extracellular matrix deposits in the alveolar sacs. Alveolar hLOs also showed structural alterations such as excessive tissue fraction under bleomycin treatment. Therefore, we suggest that micro-CT analyzable PSC-derived alveolar hLOs are a promising in vitro model to predict lung toxicity manifestations, including fibrosis.

Health-related quality of life among older adults who experienced the Pohang earthquake in South Korea: A cross-sectional survey.

BACKGROUND: Earthquakes are global natural disasters and can cause loss of property, livelihood and affect human health. A 5.4 magnitude earthquake, the Pohang earthquake, occurred in South Korea in 2017. In this study, based on a health-related quality of life (HRQOL) conceptual model, we examined the HRQOL and its associated factors among older adults who had experienced the earthquake. METHODS: A cross-sectional study was conducted with a quota sample of 312 older adults living in eight villages of a district that was the most damaged area during the Pohang earthquake. Data were collected from January 15-March 19, 2019, via face-to-face interviews using structured questionnaires. Structural equation modeling was performed to explore the associations among depression, posttraumatic stress symptoms, community resilience, social support, disaster preparedness, and HRQOL. RESULTS: The mean age of the participants was 77.93 ± 6.11 years. HRQOL scores were 49.85 ± 18.07 (physical health), 50.16 ± 18.75 (psychological health), 61.93 ± 19.20 (social relations), and 49.53 ± 16.37 (environment). The structural equation modeling analysis showed a good fit. Depression had direct (ß = - 2.21; p < 0.001), indirect (ß =- 0.23; p < 0.001), and total effects on HRQOL (ß = - 2.44; p < 0.001). Community resilience (ß = 6.05; p = 0.001) and social support (ß = 0.12, p = 0.001) had direct and total effects on HRQOL. Disaster preparedness had indirect (ß = 0.40; p = 0.001) and total (ß = 0.69, p = 0.031) effects on HRQOL. In contrast, posttraumatic stress symptoms did not have significant effects on HRQOL. CONCLUSIONS: Our findings indicated that lower depression, higher community resilience, social support, and disaster preparedness were associated with increased HRQOL. Thus, it is helpful to decrease depression and strengthen community resilience, social support, and disaster preparedness to promote HRQOL among older adults who have experienced earthquakes. These results can inform the development of HRQOL in socio-psychological improvement programs for older adults in community health centers and disaster-relief psychological support centers.

Dementia in a Hearing-impaired Population According to Hearing Aid Use: A Nationwide Population-based Study in Korea.

BACKGROUND: Hearing loss is considered a potentially modifiable risk factor for dementia. However, the effect of use of a hearing aid on the development of dementia has not been clearly established. We aimed to assess the incidence of dementia in hearing-impaired individuals according to hearing aid use in a nationwide population-based cohort study with matched controls. METHODS: This was a retrospective, longitudinal, cohort study of South Korean national claims data for individuals newly registered with hearing disabilities (better ear ≥40 dBHL with worse ear ≥80 dBHL, or better ear ≥60 dBHL) between 2004 and 2008. The hearing aid cohort comprised individuals who received hearing aid subsidies from the National Health Insurance within a year from disability registration. The comparison cohort comprised individuals without a record of a hearing aid claim during the study period after 1:1 matching for audiologic and sociodemographic factors with the hearing aid cohort. The occurrence of dementia was followed up until 2018. RESULTS: Each cohort comprised 8780 individuals. Overall incidence of dementia in the hearing aid and comparison cohorts were 156.0 and 184.5 per 10,000 person-years, respectively (incidence rate ratio = 0.85, 95% confidence interval 0.79-0.91). In a multivariable analysis of the whole study populations, hearing aid use (hazard ratio = 0.75, 95% confidence interval 0.70-0.81) attenuated the risk of dementia. CONCLUSIONS: Dementia incidence in individuals with hearing disabilities was lower in hearing aid users than that in nonusers. Hearing rehabilitation with hearing aids should be encouraged for individuals with hearing loss.

Polyhexamethylene guanidine phosphate increases stress granule formation in human 3D lung organoids under respiratory syncytial virus infection.

Polyhexamethylene guanidine phosphate (PHMG-p), a humidifier disinfectant, is known to cause lung toxicity, including inflammation and pulmonary fibrosis. In this study, we aimed to investigate the effect of PHMG-p on human lung tissue models (2D epithelial cells and 3D organoids) under conditions of oxidative stress and viral infection. The effect of PHMG-p was studied by evaluating the formation of stress granules (SGs), which play a pivotal role in cellular adaptation to various stress conditions. Under oxidative stress and respiratory syncytial virus (RSV) infection, exposure to PHMG-p remarkably increased eIF2α phosphorylation, which is essential for SG-related signalling, and significantly increased SG formation. Furthermore, PHMG-p induced fibrotic gene expression and caused cell death due to severe DNA damage, which was further increased under oxidative stress and RSV infection, indicating that PHMG-p induces severe lung toxicity under stress conditions. Taken together, toxicity evaluation under various stressful conditions is necessary to accurately predict potential lung toxicity of chemicals affecting the respiratory tract.

TREM2 promotes natural killer cell development in CD3-CD122+NK1.1+ pNK cells.

BACKGROUND: Triggering receptor expressed on myeloid cells 2 (TREM2) signaling is considered to regulate anti-inflammatory responses in macrophages, dendritic cell maturation, osteoclast development, induction of obesity, and Alzheimer's disease pathogenesis. However, little is known regarding the effect of TREM2 on natural killer (NK) cells. RESULTS: Here, we demonstrated for the first time that CD3-CD122+NK1.1+ precursor NK (pNK) cells expressed TREM2 and their population increased in TREM2-overexpressing transgenic (TREM2-TG) mice compared with that in female C57BL/6 J wild type (WT) mice. Both NK cell-activating receptors and NK cell-associated genes were expressed at higher levels in various tissues of TREM2-TG mice than in WT mice. In addition, bone marrow-derived hematopoietic stem cells (HSCs) of TREM2-TG mice (TG-HSCs) successfully differentiated into NK cells in vitro, with a higher yield from TG-HSCs than from WT-HSCs. In contrast, TREM2 signaling inhibition by TREM2-Ig or a phosphatidylinositol 3-kinase (PI3K) inhibitor affected the expression of the NK cell receptor repertoire and decreased the expression levels of NK cell-associated genes, resulting in significant impairment of NK cell differentiation. Moreover, in melanoma-bearing WT mice, injection of bone marrow cells from TREM2-TG mice exerted greater antitumor effects than that with cells from WT control mice. CONCLUSIONS: Collectively, our data clearly showed that TREM2 promoted NK cell development and tumor regression, suggesting TREM2 as a new candidate for cancer immunotherapy.

p21WAF1/CIP1 promotes p53 protein degradation by facilitating p53-Wip1 and p53-Mdm2 interaction.

Downregulation of the p53 tumor suppressor in cancers is frequently accompanied by the upregulation of Wip1 (a phosphatase) and Mdm2 (an E3 ubiquitin ligase). Mdm2 binds and ubiquitinates p53, promoting its degradation by the proteasome. As the p53/Mdm2 interaction is alleviated by the phosphorylation of the serine-15 (S15) residue of p53, Wip1, which can directly dephosphorylate phospho-S15, facilitates the Mdm2-mediated degradation of p53. Here, we found that p21WAF1/CIP1, previously shown to bind p53 and Mdm2, reduces the cellular levels of p53 protein by decreasing its stability. This is accompanied by a decrease in p53-S15 phosphorylation levels. In agreement, p21 promotes the p53/Wip1 interaction. Additionally, p21 interacts with Wip1, forming a trimeric complex of p53, p21, and Wip1. Studies using a p21 deletion mutant that cannot bind p53 revealed that the p53/p21 complex is more efficient than p53 alone in facilitating the binding of p53 to Wip1 and Mdm2. These findings indicate that p21 is a novel negative regulator of p53 stability and therefore, may be used as a target to restore p53 activity by preventing the action of Wip1 and Mdm2 on p53.

Population genetic structure of Semisulcospira gottschei: simultaneous examination of mtDNA and microsatellite markers.

Semisulcospira gottschei is an Asian endemic species inhabiting Korea and China. However, genetic structure analysis of the resource management of this species has not been performed. To investigate the genetic diversity among populations, microsatellites can be used to determine the geographic origins of marine and freshwater species. This study investigated the genetic structures of the Korean and Chinese populations of S. gottschei based on mitochondrial DNA (mtDNA) Cytochrome oxidase subunit I (COI) and polymorphic microsatellite loci developed from Semisulcospira coreana. Analysis of the mtDNA COI sequence revealed 43 haplotypes, which indicated no gene flow between the Korean and Chinese populations. To further elucidate the genetic structures of the Korean and Chinese populations, the population genetics of S. gottschei were analyzed using nine microsatellite markers. The genetic diversity analysis showed an average of 5.25 alleles per locus, with an average allelic richness of 4.02. Excessive homozygosity was found at all loci, which was expected to be due to the presence of null alleles at all loci. Populations of S. gottschei formed two separate clusters according to pairwise FST and AMOVA. Also, the UPGMA tree, PCA, STRUCTURE, and GeneClass indicated separation of the 11 populations into two clusters: Korea and China. These results have potential use in the management, restoration, and distinction of the origin country of populations.

Conditioned media from blue light-emitting diode-exposed fibroblasts have an anti-inflammatory effect in vitro.

We have previously reported the protective effects of blue light-emitting diode (BLED)-stimulated cell metabolites on cell injury. To further examine the effect of conditioned media (CM) derived from BLED (5 J/cm2)-exposed human normal fibroblasts (CMBL5) for clinical application, we have used the choline chloride and phenol red-free media and then concentrated CMBL5 using a centrifugal filter unit. The collected CMBL5-lower part (CMBL5-LO) has evaluated the inflammatory protein expression profile in LPS-stimulated RAW264.7 cells. Comprehensive metabolomic profiling of CMBL5-LO was carried out using hybrid tandem mass spectrometry. Treatment with CMBL5-LO showed the cytoprotective effect on apoptotic cell death, but rather increased apoptotic cells after treatment with CMBL5-upper part (CMBL5-UP). In addition, CMBL5-LO inhibited several chemo-attractants, including interleukin (IL)-6, macrophage inflammatory protein (MIP)-2, chemokine (C-C motif) ligand 5 (CCL5), granulocyte colony-stimulating factor (GCSF), and monocyte chemoattractant protein-1 (MCP-1) expression. Pro-inflammatory nitric oxide was decreased after CMBL5-LO treatment, but not by CMBL5-UP treatment. Interestingly, treatment with CMBL5-LO stimulated expression of heme oxygenase-1, indicating its anti-inflammatory property. Most endoplasmic reticulum (ER) stress proteins except for transcription factor C/EBP homologous protein (CHOP) were highly expressed after irradiation with BLED in cells. Further studies are needed to examine the precise mechanism by CMBL5-LO in cells.

Whitening effect of novel peptide mixture by regulating melanosome biogenesis, transfer and degradation.

Peptides are short chain of amino acids linked by peptide bonds. They are widely used as effective and biocompatible active ingredients in cosmetic industry. In this study, we developed novel peptide mixture and identified its anti-pigmentation effect on melanocytes and keratinocytes. Our results revealed that peptide mixture inhibited melanosome biogenesis through the regulation of microphthalmia-associated transcription factor, a key factor of melanogenesis in melanocytes. And we observed that peptide mixture inhibited melanosome uptake through the reduction of protease-activated receptor 2, a phagocytosis-related receptor in keratinocytes. Furthermore, peptide mixture activated autophagy system resulting in degradation of transferred melanosomes in keratinocytes. The anti-pigmentation effect of multi-targeting peptide mixture was assessed in a human skin equivalent model (MelanoDerm). Melanin contents in epidermal layer were significantly decreased by topical treatment of peptide mixture, suggesting that it can be applied as a novel cosmetics material having a whitening function.

Biochemical activity of magnesium ions on human osteoblast migration.

Magnesium is well known as a biodegradable biomaterial that has been reported to promote bone remodeling in several studies; however, the underlying biological mechanism remains unclear. In the present study, the role of magnesium ions in the migration of U-2 OS cells, which are osteoblast-like cell lines, was investigated. Magnesium treatment did not significantly alter the global transcriptome of U-2 OS cells, but increased the protein expression level of SNAI2, an epithelial-mesenchymal transition (EMT) marker. In addition, it was confirmed that the junctional site localization of Zona-occludens 1 (ZO-1), a representative tight junction protein, was destroyed by magnesium treatment; furthermore, it was determined that cytoplasmic localization increased, and alkaline phosphatase (ALP) activity increased. The obtained results on the mechanism by which magnesium is involved in osteoblast migration, which is important for fracture healing, will contribute to the understanding of the bone-formation process in patients with osteoporosis and musculoskeletal injury.

Identification of Differentially Expressed Genes Associated with Extracellular Matrix Degradation and Inflammatory Regulation in Calcific Tendinopathy Using RNA Sequencing.

Calcific tendinopathy (CT), developed due to calcium hydroxyapatite deposition in the rotator cuff tendon, mostly affects women in their 40 s and 50 s and causes severe shoulder pain. However, the molecular basis of its pathogenesis and appropriate treatment methods are largely unknown. In this study, we identified 202 differentially expressed genes (DEGs) between calcific and adjacent normal tendon tissues of rotator cuff using RNA sequencing-based transcriptome analysis. The DEGs were highly enriched in extracellular matrix (ECM) degradation and inflammation-related processes. Further, matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 13 (MMP13), two of the enzymes associated with ECM degradation, were found to be highly upregulated 25.85- and 19.40-fold, respectively, in the calcific tendon tissues compared to the adjacent normal tendon tissues. Histopathological analyses indicated collagen degradation and macrophage infiltration at the sites of calcific deposit in the rotator cuff tendon. Our study acts as a foundation that may help in better understanding of the pathogenesis associated with CT, and thus in better management of the disease.