Chiral Molecular Coating of a LiNiCoMnO2 Cathode for High-Rate Capability Lithium-Ion Batteries.

The growing demand for energy has increased the need for battery storage, with lithium-ion batteries being widely used. Among those, nickel-rich layered lithium transition metal oxides [LiNi1-x-yCoxMnyO2 NCM (1 - x - y > 0.5)] are some of the promising cathode materials due to their high specific capacities and working voltages. In this study, we demonstrate that a thin, simple coating of polyalanine chiral molecules improves the performance of Ni-rich cathodes. The chiral organic coating of the active material enhances the discharge capacity and rate capability. Specifically, NCM811 and NCM622 electrodes coated with chiral molecules exhibit lower voltage hysteresis and better rate performance, with a capacity improvement of >10% at a 4 C discharge rate and an average improvement of 6%. We relate these results to the chirally induced spin selectivity effect that enables us to reduce the resistance of the electrode interface and to reduce dramatically the overpotential needed for the chemical process by aligning the electron spins.

High-energy all-solid-state lithium batteries enabled by Co-free LiNiO2 cathodes with robust outside-in structures.

A critical current challenge in the development of all-solid-state lithium batteries (ASSLBs) is reducing the cost of fabrication without compromising the performance. Here we report a sulfide ASSLB based on a high-energy, Co-free LiNiO2 cathode with a robust outside-in structure. This promising cathode is enabled by the high-pressure O2 synthesis and subsequent atomic layer deposition of a unique ultrathin LixAlyZnzOδ protective layer comprising a LixAlyZnzOδ surface coating region and an Al and Zn near-surface doping region. This high-quality artificial interphase enhances the structural stability and interfacial dynamics of the cathode as it mitigates the contact loss and continuous side reactions at the cathode/solid electrolyte interface. As a result, our ASSLBs exhibit a high areal capacity (4.65 mAh cm-2), a high specific cathode capacity (203 mAh g-1), superior cycling stability (92% capacity retention after 200 cycles) and a good rate capability (93 mAh g-1 at 2C). This work also offers mechanistic insights into how to break through the limitation of using expensive cathodes (for example, Co-based) and coatings (for example, Nb-, Ta-, La- or Zr-based) while still achieving a high-energy ASSLB performance.

An Increase in Mucin2 Expression Is Required for Colon Cancer Progression Mediated by L1.

An induction in the expression of the cell adhesion receptor L1, a Wnt target gene, is a characteristic feature of Wnt/ß-catenin activation in colon cancer cells at later stages of the disease. We investigated the proteins secreted following L1 expression in colon cancer cells and identified Mucin2 among the most abundant secreted proteins. We found that suppressing Mucin2 expression in L1-expressing colon cancer cells inhibits cell proliferation, motility, tumorigenesis, and liver metastasis. We detected several signaling pathways involved in Mucin2 induction in L1-expressing cells. In human colon cancer tissue, Mucin2 expression was significantly reduced or lost in the adenocarcinoma tissue, while in the mucinous subtype of colon cancer tissue, Mucin2 expression was increased. An increased signature of L1/Mucin2 expression reduced the survival rate of human colon cancer patients. Thus, induction of Mucin2 expression by L1 is required during mucinous colon cancer progression and can serve as a marker for diagnosis and a target for therapy.

High-Entropy Co-Free O3-Type Layered Oxyfluoride: A Promising Air-Stable Cathode for Sodium-Ion Batteries.

Sodium-ion batteries have recently emerged as a promising alternative to lithium-based batteries, driven by an ever-growing demand for electricity storage systems. The present workproposes a cobalt-free high-capacity cathode for sodium-ion batteries, synthesized using a high-entropy approach. The high-entropy approach entails mixing more than five elements in a single phase; hence, obtaining the desired properties is a challenge since this involves the interplay between different elements. Here, instead of oxide, oxyfluoride is chosen to suppress oxygen loss during long-term cycling. Supplement to this, lithium is introduced in the composition to obtain high configurational entropy and sodium vacant sites, thus stabilizing the crystal structure, accelerating the kinetics of intercalation/deintercalation, and improving the air stability of the material. With the optimization of the cathode composition, a reversible capacity of 109 mAh g-1 (2-4 V) and 144 mAh g-1 (2-4.3 V) is observed in the first few cycles, along with a significant improvement in stability during prolonged cycling. Furthermore, in situ and ex situ diffraction studies during charging/discharging reveal that the high-entropy strategy successfully suppresses the complex phase transition. The impressive outcomes of the present work strongly motivate the pursuit of the high-entropy approach to develop efficient cathodes for sodium-ion batteries.

Downregulation of the Tumor Suppressor TFF1 Is Required during Induction of Colon Cancer Progression by L1.

The immunoglobulin family cell adhesion receptor L1 is induced in CRC cells at the invasive front of the tumor tissue, and confers enhanced proliferation, motility, tumorigenesis, and liver metastasis. To identify putative tumor suppressors whose expression is downregulated in L1-expressing CRC cells, we blocked the L1-ezrin-NF-κB signaling pathway and searched for genes induced under these conditions. We found that TFF1, a protein involved in protecting the mucus epithelial layer of the colon, is downregulated in L1-expressing cells and displays characteristics of a tumor suppressor. Overexpression of TFF1 in L1-transfected human CRC cells blocks the pro-tumorigenic and metastatic properties conferred by L1 by suppressing NF-κB signaling. Immunohistochemical analyses revealed that human CRC tissue samples often lose the expression of TFF1, while the normal mucosa displays TFF1 in goblet cells. Identifying TFF1 as a tumor suppressor in CRC cells could provide a novel marker for L1-mediated CRC development and a potential target for therapy.

COVCOG 1: Factors Predicting Physical, Neurological and Cognitive Symptoms in Long COVID in a Community Sample. A First Publication From the COVID and Cognition Study.

Since its first emergence in December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has evolved into a global pandemic. Whilst often considered a respiratory disease, a large proportion of COVID-19 patients report neurological symptoms, and there is accumulating evidence for neural damage in some individuals, with recent studies suggesting loss of gray matter in multiple regions, particularly in the left hemisphere. There are a number of mechanisms by which COVID-19 infection may lead to neurological symptoms and structural and functional changes in the brain, and it is reasonable to expect that many of these may translate into cognitive problems. Indeed, cognitive problems are one of the most commonly reported symptoms in those experiencing "Long COVID"-the chronic illness following COVID-19 infection that affects between 10 and 25% of patients. The COVID and Cognition Study is a part cross-sectional, part longitudinal, study documenting and aiming to understand the cognitive problems in Long COVID. In this first paper from the study, we document the characteristics of our sample of 181 individuals who had experienced COVID-19 infection, and 185 who had not. We explore which factors may be predictive of ongoing symptoms and their severity, as well as conducting an in-depth analysis of symptom profiles. Finally, we explore which factors predict the presence and severity of cognitive symptoms, both throughout the ongoing illness and at the time of testing. The main finding from this first analysis is that that severity of initial illness is a significant predictor of the presence and severity of ongoing symptoms, and that some symptoms during the initial illness-particularly limb weakness-may be more common in those that have more severe ongoing symptoms. Symptom profiles can be well described in terms of 5 or 6 factors, reflecting the variety of this highly heterogenous condition experienced by the individual. Specifically, we found that neurological/psychiatric and fatigue/mixed symptoms during the initial illness, and that neurological, gastrointestinal, and cardiopulmonary/fatigue symptoms during the ongoing illness, predicted experience of cognitive symptoms.

COVCOG 2: Cognitive and Memory Deficits in Long COVID: A Second Publication From the COVID and Cognition Study.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been often characterized as a respiratory disease. However, it is increasingly being understood as an infection that impacts multiple systems, and many patients report neurological symptoms. Indeed, there is accumulating evidence for neural damage in some individuals, with recent studies suggesting loss of gray matter in multiple regions, particularly in the left hemisphere. There are several mechanisms by which the COVID-19 infection may lead to neurological symptoms and structural and functional changes in the brain, and cognitive problems are one of the most commonly reported symptoms in those experiencing Long COVID - the chronic illness following the COVID-19 infection that affects between 10 and 25% of patients. However, there is yet little research testing cognition in Long COVID. The COVID and Cognition Study is a cross-sectional/longitudinal study aiming to understand cognitive problems in Long COVID. The first paper from the study explored the characteristics of our sample of 181 individuals who had experienced the COVID-19 infection, and 185 who had not, and the factors that predicted ongoing symptoms and self-reported cognitive deficits. In this second paper from the study, we assess this sample on tests of memory, language, and executive function. We hypothesize that performance on "objective" cognitive tests will reflect self-reported cognitive symptoms. We further hypothesize that some symptom profiles may be more predictive of cognitive performance than others, perhaps giving some information about the mechanism. We found a consistent pattern of memory deficits in those that had experienced the COVID-19 infection, with deficits increasing with the severity of self-reported ongoing symptoms. Fatigue/Mixed symptoms during the initial illness and ongoing neurological symptoms were predictive of cognitive performance.

Mussel-Inspired Polynorepinephrine/MXene-Based Magnetic Nanohybrid for Electromagnetic Interference Shielding in X-Band and Strain-Sensing Performance.

The current work delivers preparation of MXene-based magnetic nanohybrid coating for flexible electronic applications. Herein, we report carbon dot-triggered photopolymerized polynorepinepherene (PNE)-coated MXene and iron oxide hybrid deposited on the cellulose microporous membrane via a vacuum-assisted filtration strategy. The surface morphologies have been monitored by scanning electron microscopy analysis, and the coating thickness was evaluated by the gallium-ion-based focused ion beam method. Coated membranes have been tested against uniaxial tensile stretching and assessed by their fracture edges in order to assure flexibility and mechanical strength. Strain sensors and electromagnetic interference (EMI) shielding have both been tested on the material because of its electrical conductivity. The bending strain sensitivity has been stringent because of their fast 'rupture and reform' percolation network formation on the coated surface. Increased mechanical strength, solvent tolerance, cyclic deformation tolerance, and EMI shielding performance were achieved by decreasing interstitial membrane porosity. Considering a possible application, the membrane also has been tested against simulated static and dynamic water flow conditions that could infer its excellent robustness which also has been confirmed by elemental analysis via ICP-MS. Thus, as of nurturing the works of the literature, it could be believed that the developed material will be an ideal alternative of flexible lightweight cellulose for versatile electronic applications.

Improved Cycling Stability of LiNi0.8 Co0.1 Mn0.1 O2 Cathode Material via Variable Temperature Atomic Surface Reduction with Diethyl Zinc.

High-Ni-rich layered oxides [e.g., LiNix Coy Mnz O2 ; x > 0.5, x + y + z = 1] are considered one of the most promising cathodes for high-energy-density lithium-ion batteries (LIB). However, extreme electrode-electrolyte reactions, several interfacial issues, and structural instability restrict their practical applicability. Here, a shortened unconventional atomic surface reduction (ASR) technique is demonstrated on the cathode surface as a derivative of the conventional atomic layer deposition (ALD) process, which brings superior cell performances. The atomic surface reaction (reduction process) between diethyl-zinc (as a single precursor) and Ni-rich NMC cathode [LiNi0.8 Co0.1 Mn0.1 O2 ; NCM811] material is carried out using the ALD reactor at different temperatures. The temperature dependency of the process through advanced spectroscopy and microscopy studies is demonstrated and it is shown that thin surface film is formed at 100 °C, whereas at 200 °C a gradual atomic diffusion of Zn ions from the surface to the near-surface regions is taking place. This unique near-surface penetration of Zn ions significantly improves the electrochemical performance of the NCM811 cathode. This approach paves the way for utilizing vapor phase deposition processes to achieve both surface coatings and near-surface doping in a single reactor to stabilize high-energy cathode materials.

Carbon-Dots-Initiated Photopolymerization: An In Situ Synthetic Approach for MXene/Poly(norepinephrine)/Copper Hybrid and its Application for Mitigating Water Pollution.

The current work presents a facile and green synthesis of carbon quantum dots (C-dots), which could serve as initiators for polymerization. Herein, C-dots have been synthesized from an easily available green herb, dill leaves, by a single-step hydrothermal method. These C-dots were efficiently utilized as initiators for the photopolymerization of the polymer poly(norepinephrine) (PNE) for the first time. The photopolymerization is discussed by a factorial design, and the optimized synthesis conditions were evaluated by a third-order regression model of three reaction parameters: monomer concentration, C-dots concentration, and UV exposure time. The sign convention of the factorial design mode indicated that monomer concentration and time of exposure are the most important factors for polymerization. The photopolymerized poly(norepinephrine) was extensively studied using Fourier transform infrared (FTIR) analysis, X-ray photoelectron spectroscopy (XPS), mass spectra, scanning electron microscopy (SEM), atomic force microscopy (AFM), contact angle measurement, and thermogravimetric analysis (TGA). UV-assisted deposition of PNE on six different types of substrates was performed, and their water contact angle and surface morphology were studied to evaluate the coating. This UV-triggered polymerization technique was further applied to fabricate sandwich-like composite catalyst MXene/poly(norepinephrine)/copper nanoparticles. This catalyst displayed good performance in the reduction of 4-NP (4-nitrophenol) at ambient temperature, and the first-order rate constant of the catalysis was 9.39 × 10-3 s-1. The reusability of the catalyst was evaluated in terms of the conversion factor. After 10 catalytic cycles, the conversion to catalyze 4-NP was still greater than 91%. The catalytic performance was also evaluated in the continuous flow condition through a membrane, fabricated from a cellulose filter paper coated with MXene/poly(norepinephrine)/copper nanoparticles. This composite catalyst not only offers a practical mode for the catalytic reaction of MXene-based materials but also lays down the foundation for the development of new catalysts.

Structure and Functionality of an Alkylated LixSiyOz Interphase for High-Energy Cathodes from DNP-ssNMR Spectroscopy.

Degradation processes at the cathode-electrolyte interface are a major limitation in the development of high-energy lithium-ion rechargeable batteries. Deposition of protective thin coating layers on the surface of high-energy cathodes is a promising approach to control interfacial reactions. However, rational design of effective protection layers is limited by the scarcity of analytical tools that can probe thin, disordered, and heterogeneous phases. Here we propose a new structural approach based on solid-state nuclear magnetic resonance spectroscopy coupled with dynamic nuclear polarization (DNP) for characterizing thin coating layers. We demonstrate the approach on an efficient alkylated LixSiyOz coating layer. By utilizing different sources for DNP, exogenous from nitroxide biradicals and endogenous from paramagnetic metal ion dopants, we reveal the outer and inner surface layers of the deposited artificial interphase and construct a structural model for the coating. In addition, lithium isotope exchange experiments provide direct evidence for the function of the surface layer, shedding light on its role in the enhanced rate performance of coated cathodes. The presented methodology and results advance us in identifying the key properties of effective coatings and may enable rational design of protective and ion-conducting surface layers.

A Necessary Role for Increased Biglycan Expression during L1-Mediated Colon Cancer Progression.

Aberrant activation of Wnt/ß-catenin signaling and downstream ß-catenin-TCF target genes is a hallmark of colorectal cancer (CRC) development. We identified the immunoglobulin-like cell adhesion receptor L1CAM (L1) as a target of ß-catenin-TCF transactivation in CRC cells. Overexpression of L1 in CRC cells confers enhanced proliferation, motility, tumorigenesis, and liver metastasis, and L1 is exclusively localized at invasive areas of human CRC tissue. Several genes are induced after L1 transfection into CRC cells by a mechanism involving the L1-ezrin-NF-κB pathway. We conducted a secretomic analysis of the proteins in the culture medium of L1-overexpressing CRC cells. We detected a highly increased level of biglycan, a small leucine-rich ECM component, and a signaling molecule. We found that induction of biglycan is required for the cellular processes conferred by L1, including enhanced proliferation, motility, tumorigenesis, and liver metastasis. The suppression of endogenous biglycan levels or a point mutation in the L1 ectodomain that regulates cell-cell adhesion mediated by L1 blocked the enhanced tumorigenic properties conferred by L1. The mechanism of biglycan induction by L1 involves the L1-NF-κB pathway. Blocking NF-κB signaling in L1 expressing cells suppressed the induction of biglycan and the tumorigenic properties conferred by L1. Biglycan expression was undetectable in the normal colonic mucosa, but expressed at highly increased levels in the tumor tissue, especially in the stroma. The therapeutic strategies to target biglycan expression might provide a useful approach for CRC treatment in L1-overexpressing tumors.

Nonhistone human chromatin protein PC4 is critical for genomic integrity and negatively regulates autophagy.

Multifunctional human transcriptional positive co-activator 4 (PC4) is a bona fide nonhistone component of the chromatin and plays a pivotal role in the process of chromatin compaction and functional genome organization. Knockdown of PC4 expression causes a drastic decompaction which leads to open conformation of the chromatin, and thereby altered nuclear architecture, defects in chromosome segregation and changed epigenetic landscape. Interestingly, these defects do not induce cellular death but result in enhanced cellular proliferation, possibly through enhanced autophagic activity. Moreover, PC4 depletion confers significant resistance to gamma irradiation. Exposure to gamma irradiation further induced autophagy in these cells. Inhibition of autophagy by small molecule inhibitors as well as by silencing of a critical autophagy gene drastically reduces the ability of PC4 knockdown cells to survive. On the contrary, complementation with wild-type PC4 could reverse this phenomenon, confirming the process of autophagy as the key mechanism for radiation resistance in the absence of PC4. These data connect the unexplored role of chromatin architecture in regulating autophagy during stress conditions such as radiation.

KLF4 expression in the surgical cut margin is associated with disease relapse of oral squamous cell carcinoma.

OBJECTIVE: The presence of cancer stem-like cells (CSCs) in the majority of tumors is one of the factors responsible for disease relapse in oral squamous cell carcinoma (OSCC). In this study, we investigated the role of octamer-binding transcription factor 4 (OCT4) and Kruppel-like factor 4 (KLF4) in OSCC progression and disease relapse. STUDY DESIGN: In this study, 102 patients with OSCC were included. The expression of ß-catenin and CSC markers (KLF4 and OCT4) in surgical cut margin and tumor were investigated through Western blot analysis, immunohistochemistry, and quantitative polymerase chain reaction analysis. The χ2 test was used to evaluate the association of ß-catenin, OCT4, and KLF4 expression with clinicopathologic characteristics. Kaplan-Meier and Cox regression analyses were performed to correlate different clinical factors with the prognoses of patients with OSCC. RESULTS: We observed increased expression of OCT4, KLF4, and ß-catenin in the cut margins (CMs) in recurrent OSCC. The χ2 test exhibited recurrence as one of the key factors associated with high expression of these markers. Kaplan-Meier and COX regression analyses demonstrated that increased expression of KLF4 in the CM region of recurrent patients was independently associated with a poor prognosis. CONCLUSIONS: Our findings indicated that expression of KLF4 can be used for monitoring disease progression and may serve as prognostic marker to predict recurrence.

Radiation-induced DNA damage response and resistance in colorectal cancer stem-like cells.

Purpose: Radiation therapy is an integral part of current treatment modality for colorectal cancer. Recent studies have revealed the presence of cancer stem-like cells (CSCs) population, in different tumors are responsible for therapeutic resistance and disease relapse, including colorectal cancer with poorer survival rate. Hence, characterization of the effect of Ionizing Radiation (IR) in colorectal cancer may serve to explain possible mechanisms. Material and methods: Parental HCT116 and HCT-15 cells and derived colonospheres were irradiated and dose was optimized based on cell survival assay and cell cycle analysis. DNA damage response (DDR) was elucidated by γH2AX foci formation, COMET assay, and ATM, p-ATM, ERCC1 expression post-treatment. The expression level of developmental marker (ß-catenin), CSC markers (CD44, KLF4) and telomeric components (TRF2, RAP1, hTERT) were evaluated. Results: We observed cell survival was more in colonospheres post-irradiation and also exhibited decreased γH2AX foci, olive tail moment, increased ERCC1, and p-ATM expression than its parental counterpart which corresponds to efficient DDR. Differential expression of developmental marker, CSC markers, and telomeric components were observed after irradiation. Conclusion: This study highlighted the presence of CSC phenotype in colonospheres having increased DNA repair capacity. Differential expression of developmental marker, CSC markers and telomeric components between parental and colonospheres may contribute in radio-resistance property of CSCs.

p38 MAPK pathway and its interaction with TRF2 in cisplatin induced chemotherapeutic response in head and neck cancer.

TRF2 is a telomere binding protein, a component of the shelterin complex that plays a major role in maintaining the integrity of the genome. TRF2 is over-expressed in a number of human cancers including Head and Neck cancer and might play a key role in tumor initiation and development. p38 MAPK signaling pathway is strongly activated in response to various environmental and cellular stresses and thus overexpressed in most of the Head and Neck cancer cases. In this study, we investigated potential interactions of TRF2 with p38 in HNSCC cells and patient samples. Using in silico experiments, we identified interface polar residue Asp-354 of p38 and Arg-492, Arg-496 of TRF2 as protein-protein interaction hotspots. In addition to these interactions, Arg-49 residue of p38 was also found to interact with Glu-456 of TRF2. A detailed understanding of how phosphorylated and unphosphorylated state of p38 protein can influence the stability, specificity and to some extent a conformational change of p38-TRF2 binding is presented. Silencing of TRF2 significantly decreased the phosphorylation of p38 in HNSCC cells which was confirmed by western blot, immunofluorescence and co-immunoprecipitation and alternatively inhibiting p38 using p38 inhibitor (SB 203580) decreased the expression of TRF2 in HNSCC cells. Furthermore, we checked the effect of TRF2 silencing and p38 inhibition in cisplatin induced chemosensitivity of SCC-131 cells. TRF2 silencing and p38 inhibition chemosensitize HNSCC cells to cisplatin. Thus, targeting TRF2 in combinatorial therapeutics can be a treatment modality for Head and Neck cancer which involves inhibition of p38 MAPK pathway.

Hydrogenation of Furfural with Nickel Nanoparticles Stabilized on Nitrogen-Rich Carbon Core-Shell and Its Transformations for the Synthesis of γ-Valerolactone in Aqueous Conditions.

In this article, we report the synthesis of nitrogen-rich carbon layer-encapsulated Ni(0) nanoparticles as a core-shell structure (Ni@N/C-g-800) for the catalytic hydrogenation of furfural to furfuryl alcohol. The nickel nanoparticles were stabilized by the nitrogen-rich graphitic framework, which formed during the agitation of nickel acetate-impregnated cucurbit[6]uril surface in a reducing atmosphere. Furthermore, the catalyst was characterized using various physicochemical methods such as powder X-ray diffraction, Raman, field emission-scanning electron microscopy, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, Brunauer-Emmett-Teller surface area, CO2-temperature-programmed desorption, inductive coupled plasma, and CHN analyses. The nitrogen-rich environment of the solid support with metallic Ni nanoparticles was found to be active and selective for the catalytic hydrogenation of furfural with molecular H2 in an aqueous medium at 100 °C. To understand the reaction mechanism, the diffuse reflectance infrared Fourier transform study was performed, which revealed that the C═O bond is activated in the presence of a catalyst. In addition, we have extended our methodology toward the synthesis of "levulinic acid" and "γ-valerolactone", by successive hydrolysis and hydrogenation of furfuryl alcohol and levulinic acid, respectively, in an aqueous medium. Moreover, the heterogeneous catalysts used in all of the three consecutive steps help in recovery and recycling of the catalyst and easy separation of products.

Role of Telomeric TRF2 in Orosphere Formation and CSC Phenotype Maintenance Through Efficient DNA Repair Pathway and its Correlation with Recurrence in OSCC.

The major problem to effective treatment of oral cancer is the presence of therapy resistance. Presence of cancer stem cell in the bulk of tumor have been implicated in therapeutic resistance. In this study, we report a non-telomeric role of TRF2 in formation of oral cancer spheroids and CSC phenotype maintenance via an efficient DNA damage repair mechanism in the presence of chemotherapeutic insult. We report reduced sphere formation efficiency and reduced spheroid size in TRF2 silenced oral cancer cell lines. TRF2 silenced orospheres further reported reduced proliferative capacity as compared to non-silenced orospheres. Furthermore, TRF2 silencing hampered the migratory potential of oral cancer cell line and also reduced the expression of several CSC markers like CD44, Oct4, Sox2, KLF4 and c-Myc along with ß-catenin and hTERT molecules both in Cal27 cell line and generated orospheres. TRF2 silencing impaired efficient DNA damage repair capacity of non-orospheric and orospheric cells and repressed ERCC1 expression levels when treated with Cisplatin. TRF2 overexpression was also observed to correlate with poor overall survival and disease relapse of OSCC patients. In silico studies further identified several amino acid residues that show high binding affinity and strong protein-protein interactions among TRF2 and CSC marker KLF4. Hence, our report confirms a non-telomeric role of TRF2 in spheroid generation, maintenance of CSC phenotype and efficient DNA damage repair capacity contributing to chemotherapy resistance in oral cancer cell line. We further iterate the use of TRF2 as a prognostic marker in OSCC for faster detection and improved survival.

Role of p38 MAPK in disease relapse and therapeutic resistance by maintenance of cancer stem cells in head and neck squamous cell carcinoma.

AIM: This study aimed to investigate the role of p38 MAPK in maintenance of cancer stem cell (CSC) phenotype, therapy resistance, and DNA damage repair and response in head and neck squamous cell carcinoma (HNSCC). METHODS: In this study, 104 HNSCC patients were included. Western blot, immunohistochemistry, and qPCR analysis were performed to investigate the expression level of p-p38 and CSC markers in cut margin and tumor area of HNSCC patients. The expression level of p-p38 and CSC markers was also evaluated in HNSCC cells with or without p38 inhibitor. Chemoresistance, wound healing capacity, and multicellular tumor spheroids (MCTS) formation capacity were evaluated in HNSCC-derived cell lines with or without p38 inhibitor. In addition, DNA damage response and repair capacities were also evaluated in HNSCC cells after p38 inhibition using alkaline comet assay and γ-H2 AX immunostaining. RESULT: We observed that recurrence could be associated with upregulated status of p-p38 and p38α gene in cut margin area of HNSCC patients as compared to tumor region. p38-inhibited cells showed significantly reduced expression of CSC markers, chemosensitivity toward cisplatin, reduced migration potential, and sphere-forming ability along with increased apoptotic population after treatment with increasing concentration of cisplatin. p38-inhibited cells also exhibited significantly increased comet olive tail moment and accumulation of γ-H2 AX, demonstrating increased DNA damage. CONCLUSION: This study demonstrated that p38 MAPK activation may play a role in therapeutic resistance and disease relapse in HNSCC by maintenance of CSCs phenotype.

Role of ß-catenin in cisplatin resistance, relapse and prognosis of head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of cancer in India with high incidence and rapid recurrence rates. Here, we aimed to investigate the role of ß-catenin, a developmental pathway gene, in HNSCC therapy resistance, DNA damage response, recurrence and prognosis. METHODS: In total 80 HNSCC samples were included. Western blot, immunohistochemistry and qRT-PCR analyses were performed to assess ß-catenin expression in the cut margin and tumor areas of each sample. Kaplan-Meier analyses were performed to correlate ß-catenin expression with the survival and prognosis of HNSCC patients. In addition, chemo-resistance, DNA damage response and DNA repair capacities were evaluated in HNSCC-derived cell lines through LiCl-mediated up-regulation and siRNA-mediated silencing of ß-catenin expression. RESULTS: We observed ß-catenin up-regulation in cut margin areas of recurrent patients compared to their corresponding tumor regions, which subsequently could be associated with poor prognosis. In addition, we found that LiCl-mediated up-regulation of ß-catenin in HNSCC-derived cells led to cisplatin resistance, evasion of apoptosis, enhanced DNA repair and enhanced migration. The effects of ß-catenin silencing correlated with its putative role in chemo-resistance and DNA damage response. CONCLUSION: From our results we conclude that ß-catenin may contribute to HNSCC therapy resistance and disease relapse. As such, ß-catenin may be explored as a therapeutic target along with conventional therapeutics.