Identification of novel genetic variants associated with oral squamous cell carcinoma (OSCC) in South-West coast of India using targeted exome sequencing.

Oral squamous cell carcinoma (OSCC) is a subset of head and neck squamous cell carcinoma (HNSCC). This study explores the genetic landscape of oral squamous cell carcinoma (OSCC) in a cohort of 33 patients from Southern India using targeted exome sequencing. Our analysis revealed a diverse range of mutations across the cohort, with missense mutations being the most prevalent. Pathogenic mutations, as classified by ClinVar, exhibited significant individual variation, highlighting the heterogeneity of OSCC. Seventy-five genes were identified to harbor pathogenic or potentially pathogenic mutations, with notable recurrence in genes such as TP53, PDGFRA, and RAD50 among others. Comparison with high-frequency mutation genes in HNSCC from TCGA database revealed significant overlap, emphasizing the relevance of these mutations across different populations. Additionally, several novel mutations were identified, including those in CHD8, ITPKB, and HNF1A, shedding light on potential genetic risk factors specific to this population. Functional annotation and pathway analysis underscored the involvement of these mutated genes in various cancer-related pathways. Despite limitations such as sample size and the need for further validation, this study contributes to a deeper understanding of OSCC pathogenesis and highlights potential genetic markers for prognosis and targeted interventions, especially in the Indian context.

Biocompatibility of polymethyl methacrylate heat-polymerizing denture base resin copolymerized with antimicrobial monomers.

STATEMENT OF PROBLEM: Quaternary ammonium (QA)-based monomers such as dimethyl-hexadecyl-methacryloxyethyl-ammonium iodide (DHMAI) and 2-dimethyl-2-dodecyl-1-methacryloxyethyl ammonium iodine (DDMAI) have been investigated as copolymerizable monomers to impart antimicrobial activity to dental restorative and prosthetic materials. However, the biocompatibility of these antimicrobial monomers needs to be investigated in vivo before their clinical use. PURPOSE: The purpose of this study was to assess the in vivo biocompatibility of polymethyl methacrylate (PMMA) heat-polymerizing denture base resin copolymerized with varying concentrations of DHMAI and DDMAI. MATERIAL AND METHODS: The toxicity and genotoxicity of the antimicrobial monomers (DHMAI 5 µg/mL and DDMAI 20 µg/mL) at 1 to 100 µg/mL concentrations were investigated against zebrafish embryos (Danio rerio, n=10) using a zebrafish embryotoxicity test (ZET) or fish embryotoxicity test (FET) and comet assay, respectively. Further, DHMAI 5 µg/mL and DDMAI 20 µg/mL were incorporated into a conventional PMMA denture base system and a similar test was done on specimens of modified PMMA resin. For the evaluation of in vivo biocompatibility, modified PMMA specimens were subcutaneously implanted into Wistar rats (n=6) and biochemical, hematological, and histopathological parameters were investigated. Results were analyzed and compared using ANOVA and the Tukey post hoc test (α=.05). RESULTS: Toxicity and genotoxicity studies using zebrafish embryos revealed that the incorporation of monomer to PMMA did not increase the toxicity, as confirmed by post-hour fertilization. Modified PMMA did not affect the hematological parameters, such as red blood cell (RBC) and white blood cell (WBC) except for the platelet count, which was significantly increased (P<.001), and the biochemical parameter, such as total protein (TP), blood urea nitrogen (BUN), serum glutamic-oxaloacetic transaminase (SGOT), triglyceride (TG), creatinine (Crea), total cholesterol, and serum glutamic pyruvic transaminase (SGPT), except for high-density lipoprotein (HDL) cholesterol, which was significantly decreased (P<.01). Histopathologically, no changes were observed in the sections of the liver, kidney, spleen, and subcutaneous tissues in the modified PMMA implanted rats. Additionally, no significant variation was found in the expression of immunohistochemical marker tumor necrosis factor alpha (TNF-α), confirming the noninflammatory response exerted by the modified PMMA on experimental rats. CONCLUSIONS: Zebrafish embryos treated with modified PMMA specimens demonstrated favorable biological properties and did not exhibit significant cytotoxicity and genotoxicity. Subcutaneously implanted modified PMMA did not cause any major hematological, biochemical, and histopathological alterations in Wistar albino rats, thus confirming the biocompatibility of PMMA heat-polymerizing denture base resin incorporated with DHMAI and DDMAI for dental applications.

Design, synthesis and evaluation of new thiazolidin-4-ones as LPA1 receptor antagonists for breast cancer therapy.

Aim: Breast cancer has been a leading cause of mortality among women worldwide in recent years. Targeting the lysophosphatidic acid (LPA)-LPA1 pathway using small molecules could improve breast cancer therapy. Materials & methods: Thiazolidin-4-ones were developed and tested on MCF-7 cancer cells, and active compounds were analyzed for their effects on apoptosis, migration angiogenesis and LPA1 protein and gene expression. Results & conclusion: Compounds TZ-4 and TZ-6 effectively reduced the migration of MCF-7 cells, and induced apoptosis. TZ-4, TZ-6, TZ-8 and TZ-14 significantly reduced the LPA1 protein, LPA1 and angiogenesis gene expression in treated MCF-7 cells. Molecular docking and molecular dynamic simulation studies reveal the ligand interactions and stability of the LPA1-ligand complex. Developed thiazolidin-4-ones showed great potential as an LPA1-targeted approach to combating breast cancer.

Breast cancer is a major cause of death for women worldwide. Using small molecules to target the lysophosphatidic acid (LPA)­LPA₁ pathway could improve breast cancer treatment. We tested a type of molecule called thiazolidin-4-ones on breast cancer cells in the lab. We looked at how these molecules affected cell death, movement, blood vessel growth and the activity of the LPA₁ gene and protein. Some of these molecules, such as TZ-4 and TZ-6, reduced the movement of cancer cells and caused them to die. They also decreased the levels of LPA₁ protein and gene activity in the cells. We used computer simulations to see how these molecules interacted with the LPA₁ protein. Our findings suggest that thiazolidin-4-ones could be a promising treatment for breast cancer by targeting LPA₁.

Braided silk sutures coated with photoreduced silver nanoparticles for eradicating Staphylococcus aureus and Streptococcus mutans infections.

BACKGROUND: Infections resulting from surgical procedures and wound closures continue to pose significant challenges in healthcare settings. To address this issue, the investigators have developed antibacterial non-resorbable braided silk sutures using in situ deposited silver nanoparticles (AgNPs) and investigated their efficacy in eradicating Staphylococcus aureus and Streptococcus mutans infections. METHODS: The braided silk sutures were modified through a simple and efficient in situ photoreduction method, resulting in the uniform distribution of AgNPs along the suture surface. The synthesized AgNPs were characterized using scanning electron microscopy (SEM), dynamic light scattering analysis (DLS) and Fourier Transform Infrared Spectroscopy analysis (FTIR) confirming their successful integration onto the silk sutures. The antibacterial activity of the nanoparticle coated sutures were compared and evaluated with non-coated braided silk sutures through in vitro assays against both S. aureus and S. mutans. RESULTS: The surface and cross-sectional analysis of the treated sutures revealed a uniform and homogeneous distribution of silver particles achieved through the photoreduction of silver solution. This observation confirms the successful coating of silver nanoparticles (AgNPs) on the sutures. The antimicrobial studies conducted, demonstrated significant reductions in bacterial colonies when exposed to the silver nanoparticle-coated sutures. Notably, the width of the inhibition zone surrounding the coated sutures remained consistently wide and stable for duration up to 7 days. This sustained and robust inhibitory effect against gram-positive bacteria, specifically S. aureus and S. mutans, serves as strong evidence of the antibacterial efficacy of the coated sutures. CONCLUSION: The coating of silk sutures with AgNPs provided a significant and effective antibacterial capacity to the surgical sutures, with this activity being sustained for a period of 7 days. This suggests that AgNPs-in situ photoreduction deposited sutures have the potential to effectively manage S. aureus and S. mutans infections.

In vitro blood brain barrier models: Molecular aspects and therapeutic strategies in glioma management.

Glioma management is the most challenging task in clinical oncology due to numerous reasons. One of the major hurdles in glioma therapy is the presence of blood brain barrier which resists the entry of most of the drugs into the brain. However, in case of tumors, blood brain barrier integrity is compromised, which in turn can be advantageous in delivering the drugs, if the therapeutic module is strategically modified. For such improvised therapeutic strategy, it is necessary to understand the molecular composition and profiling of blood brain barrier and blood brain tumor barrier. This review mainly focuses on the composition, markers expressed on the blood brain barrier which will help the readers to understand its basic environment. It also gives a detailed account of the various in vitro models that are used to study the nature of the blood brain barrier and describes various strategies in improvising the drug delivery in glioma management.

Cytotoxic and apoptotic efficacy of Alkanna tinctoria on glioma cells.

Glioblastoma is the most common lethal form of malignant tumor that arises from the central nervous system. The present-day therapeutic strategies possess their own pros and cons. Hence, there is a need to look back into the traditional medicines that could be potential agents to treat glioblastoma. One of the potential approaches in anticancer therapy is to induce tumor cell death by natural phytochemicals which pose minimum adverse effects. In this study, we aimed to evaluate the cytotoxic and apoptotic effects of hexane extract of Alkanna tinctoria (L.) Tausch on U87MG cells using various biological activities. The results obtained from our study state that the plant extract showed potential anticancer activity against U87MG cells. The molecular docking studies indicated that alkannin and shikonin present in the extract could efficiently bind to brain tumor cell receptors and showed better docking scores when compared to commercially available drugs temozolomide and bevacizumab.

AgVI and Ag/ZnOVI nanostructures from Vateria indica (L.) exert antioxidant, antidiabetic, anti-inflammatory and cytotoxic efficacy on triple negative breast cancer cells in vitro.

Human triple-negative breast cancer (TNBC) being an aggressive cancer type accounts for about 15-20% of global breast cancer cases. In the present study, the cytotoxicity of pure silver (AgVI) and silver/zinc oxide (Ag/ZnOVI) nanostructures was evaluated against the TNBC cells. The nanostructures synthesized from a green route using Vateria indica (L.) fruit extract were characterized to scrutinize their formation, crystal phase, size, shape, and surface properties via FTIR, PXRD, FE-SEM coupled with EDS spectroscopy, and BET analysis. The results of the studies have unveiled the formation of 26.43 nm and 20.97 nm sized AgVI and Ag/ZnOVI nanostructures in their purest form. The in-vitro anticancer study performed on human TNBC cells [MDA-MB468] revealed the enhancement in the antiproliferative potentiality of bimetallic Ag/ZnOVI nanostructures from 66.99 ± 0.13 to 79.73 ± 0.23 in comparison to pure AgVI nanostructures. In addition to this, the greenish yellow-fluorescence observed in the TNBC nuclei during the AO-EB staining study manifested the early apoptosis. Furthermore, the anti-inflammatory and cytotoxicity study performed on the human RBC and normal NIH3T3 murine fibroblasts cells proved the biocompatibility and non-toxic nature of the synthesized nanostructures with membrane stabilization percentage up to 94.5 ± 0.001. Additionally, the antioxidant and antidiabetic studies carried out have corroborated the radical scavenging and α-amylase inhibition capability up to 85.87 ± 0.001 and 89.60 ± 0.002 % respectively. Thus the overall results of the study substantiate the superlative antioxidant, antidiabetic, and antiproliferative property of green synthesized AgVI and Ag/ZnOVI nanostructures with excellent biocompatibility.

Anti-angiogenic, apoptotic and matrix metalloproteinase inhibitory activity of Withania somnifera (ashwagandha) on lung adenocarcinoma cells.

INTRODUCTION: Withania somnifera belongs to the family Solanaceae, known as Queen of medicinal plants for its enormous use in the medicinal field. Traditionally ashwagandha is used to treat several neurological disorders. This study evaluates the cytotoxic, apoptotic, antiangiogenic and matrix metalloproteinase (MMP) inhibitory activity of W. somnifera on lung adenocarcinoma. METHODOLOGY: Aqueous and ethanolic extracts were prepared from the roots of the W. somnifera. Qualitative and quantitative phytochemical analyses were performed using the standard protocols. Cytotoxicity was assessed using MTT assay. Further experiments were carried out with IC50 concentration of the extract. Apoptosis and DNA damage were evaluated using AO-EB dual staining, Hoechst staining and Comet assay. Effect of the extract on cell migration was evaluated using scratch assay. Angiogenesis inhibition was evaluated using in ovo CAM assay and angiogenic pathway alterations were evaluated using qRT-PCR and western blotting. Autophagy induction was studied via western blotting. RESULTS: In this study, we found antioxidant activity and the presence of certain secondary metabolites in the ethanolic extracts. The extract showed cytotoxic activity on lung adenocarcinoma cells with an IC50 of 99.7 µg/ml. The extract showed significant anti-angiogenic, apoptotic and autophagy induction activity. W. somnifera extract induced significant decrease in the cell migration at lower concentrations indicating the anti-migratory potential. CONCLUSION: Our investigation revealed ethanolic extract of W. somnifera possess significant anti-angiogenic and MMP inhibitory activity and helps in inhibiting the lung adenocarcinoma cells proliferation. Further, our study revealed that the enhanced autophagy induction and apoptotic effects of W. somnifera are responsible for the potential anticancer activity of the extract.

Bio-corrosion impacts on mechanical integrity of ZM21 Mg for orthopaedic implant application processed by equal channel angular pressing.

The mechanical integrity of rolled ZM21 Mg was improved by equal channel angular pressing (ECAP) to function as a potential biodegradable bone screw implant. Electron backscattered diffraction (EBSD) revealed deformed grains of 45 µm observed in rolled ZM21 Mg. They were transformed to equiaxed fine grains of 5.4 µm after 4th pass ECAP. The yield strength of rolled and ECAPed ZM21 Mg alloys were comparable. In contrast, 4th pass ZM21 Mg exhibited relatively higher elongation when compared to rolled sample. The mechanical properties of rolled and ECAPed ZM21 Mg were dependant on both grain refinement and crystallographic texture. The rolled and 4th pass ECAPed tensile samples exhibited nonlinear deterioration of mechanical properties when tested after 7, 14, 21 and 28 days immersion in Hank's solution. The evaluation signifies that regardless their processing condition, ZM21 Mg alloys are suitable for surgical areas that requires high mechanical strength. In addition, the 4th pass ECAP samples were viable to MG-63 cells proving themselves to be promising candidates for future in vivo studies.

The unique molecular targets associated antioxidant and antifibrotic activity of curcumin in in vitro model of acute lung injury: A proteomic approach.

Bleomycin (BLM) injury is associated with the severity of acute lung injury (ALI) leading to fibrosis, a high-morbidity, and high-mortality respiratory disease of unknown etiology. BLM-induced ALI is marked by the activation of a potent fibrogenic cytokine transcription growth factor beta-1 (TGFß-1), which is considered a critical cytokine in the progression of alveolar injury. Previously, our work demonstrated that a diet-derived compound curcumin (diferuloylmethane), represents its antioxidative and antifibrotic application in TGF-ß1-mediated BLM-induced alveolar basal epithelial cells. However, curcumin-specific protein targets, as well as its mechanism using mass spectrometry-based proteomic approach, remain elusive. To elucidate the underlying mechanism, a quantitative proteomics approach and bioinformatics analysis were employed to identify the protein targets of curcumin in BLM or TGF-ß1-treated cells. With subsequent in vitro experiments, curcumin-related pathways and cellular processes were predicted and validated. The current study discusses two separate proteomics experiments using BLM and TGF-ß1-treated cells with the proteomics approach, various unique target proteins were identified, and proteomic analysis revealed that curcumin reversed the expressions of unique proteins like DNA topoisomerase 2-alpha (TOP2A), kinesin-like protein (KIF11), centromere protein F (CENPF), and so on BLM or TGF-ß1 injury. For the first time, the current study reveals that curcumin restores TGF-ß1 induced peroxisomes like PEX-13, PEX-14, PEX-19, and ACOX1. This was verified by subsequent in vitro assays. This study generated molecular evidence to deepen our understanding of the therapeutic role of curcumin at the proteomic level and may be useful to identify molecular targets for future drug discovery.

Unravelling the human triple negative breast cancer suppressive activity of biocompatible zinc oxide nanostructures influenced by Vateria indica (L.) fruit phytochemicals.

The present study delineates the biosynthesis of ZnOVI nanostructures by using aqueous fruit extract of V. indica. The study has disclosed the role of V. indica fruit extract as both reducing and capping agents, ushering the formation of ZnOVI nanostructures with distinct morphologies. The formation of ZnOVI nanostructures was corroborated by FT-IR and UV-visible spectroscopy which was further substantiated by the elemental composition study through EDS spectroscopy. The nanostructures were also investigated by Rietveld refinement of PXRD data, FE-SEM, and BET analysis. The morphology, size, and surface area were found to be precursor stoichiometry dependent. The in-vitro cytotoxicity study of ZnOVI nanostructures carried out on MDA-MB468 human triple-negative breast cancer (TNBC) cells has revealed their potential cytotoxicity (91.18 ± 1.98). MTT assay performed on the NIH3T3 mouse fibroblast cells has unfolded the non-toxic nature of ZnOVI nanostructures. Additionally, the results of the AO-EB dual staining assay indicated early apoptosis in TNBC cells by displaying greenish yellow-fluorescence in the nuclei. Reactive oxygen species (ROS) measurement study has confirmed the elevated intracellular levels of ROS, supporting the oxidative-stress induced cytotoxicity in ZnOVI nanostructures treated TNBC cells. Furthermore, the haemocompatibility of ZnOVI nanostructures was evaluated using human erythrocytes. Thus, the obtained results have shown greater potential in the anticancer activity of bio-fabricated ZnOVI nanostructures.

Combining Angiogenesis Inhibitors with Radiation: Advances and Challenges in Cancer Treatment.

BACKGROUND: Radiation therapy is a widely employed modality that is used to destroy cancer cells, but it also tends to induce changes in the tumor microenvironment and promote angiogenesis. Radiation, when used as a sole means of therapeutic approach to treat cancer, tends to trigger the angiogenic pathways, leading to the upregulation of several angiogenic growth factors such as VEGF, bFGF, PDGF and angiogenin. This uncontrolled angiogenesis leads to certain angiogenic disorders like vascular outgrowth and an increase in tumor progression that can pose a serious threat to patients. OBJECTIVE: This review emphasizes on various components of the tumor microenvironment, angiogenic growth factors and biological effects of radiation on tumors in provoking the relapse. It also describes the angiogenic mechanisms that trigger the tumor relapse after radiation therapy and how angiogenesis inhibitors can help in overcoming this phenomenon. It gives an overview of various angiogenesis inhibitors in pre-clinical as well as in clinical trials. CONCLUSION: The review focuses on the beneficial effects of the combinatorial therapeutic approach of anti-angiogenesis therapy and radiation in tumor management.

Curcumin Targets p53-Fibrinolytic System in TGF-ß1 Mediated Alveolar Epithelial Mesenchymal Transition in Alveolar Epithelial Cells.

AIMS: We aim to investigate curcumin interaction with p53-fibrinolytic system, smad dependent and independent pathways underlying their prime role during lung injury and fibrosis. BACKGROUND: Curcumin, an active component of Curcuma longa plant, substantially modulates respiratory conditions. TGF-ß1 plays a central role in lung remodeling by balancing extracellular matrix (ECM) production and degradation, which is a hallmark for alveolar EMT. However, the crosstalk of curcumin is not known yet with TGF- ß1 mediated p53-Fibrinolytic system regulating alveolar EMT leading to IPF. In the present study, the potential molecular mechanism of curcumin in TGF-ß1 mediated p53-fibrinolytic system in basal alveolar epithelial cells was explored. OBJECTIVES: To understand the potential molecular mechanism of curcumin in TGF-ß1 mediated p53-fibrinolytic system in basal alveolar epithelial cells. METHODS: Basal alveolar epithelial cells were treated with TGF- ß1 to induce alveolar EMT and after 24 hrs curcumin was administered to study its anti-fibrotic effects. Molecular techniques like immunoblot, RT-PCR and immunofluorescence were performed to assess the anti-fibrotic role of curcumin on EMT markers, IL-17A, p53-smad interaction to investigate the anti-fibrotic role of curcumin. RESULTS: The results indicated that TGF-ß1-induced EMT in A549 cells exhibited altered expression of the IL-17A, p53-fibrinolytic markers and EMT markers at the mRNA and protein level. Intervention with curcumin attenuated alveolar EMT and inactivated TGF-ß1 induced Smad/non Smad signaling pathways via blocking p53-fibrinolytic system. CONCLUSION: This study provides the first evidence of the dynamic response of curcumin on TGF- ß1 mediated p53-fibrinolytic system during alveolar injury in vitro.

Bioresponsive supramolecular hydrogels for hemostasis, infection control and accelerated dermal wound healing.

Injectable, drug-releasing hydrogel scaffolds with multifunctional properties including hemostasis and anti-bacterial activity are essential for successful wound healing; however, designing ideal materials is still challenging. Herein, we demonstrate the fabrication of a biodegradable, temperature-pH dual responsive supramolecular hydrogel (SHG) scaffold based on sodium alginate/poly(N-vinyl caprolactam) (AG/PVCL) through free radical polymerization and the subsequent chemical and ionic cross-linking. A natural therapeutic molecule, tannic acid (TA)-incorporated SHG (AG/PVCL-TA), was also fabricated and its hemostatic and wound healing efficiency were studied. In the AG/PVCL-TA system, TA acts as a therapeutic molecule and also substitutes as an effective gelation binder. Notably, the polyphenol-arm structure and diverse bonding abilities of TA can hold polymer chains through multiple bonding and co-ordinate cross-linking, which were vital in the formation of the mechanically robust AG/PVCL-TA. The SHG formation was successfully balanced by varying the composition of SA, VCL, TA and cross-linkers. The AG/PVCL-TA scaffold was capable of releasing a therapeutic dose of TA in a sustained manner under physiological temperature-pH conditions. AG/PVCL-TA displayed excellent free radical scavenging, anti-inflammatory, anti-bacterial, and cell proliferation activity towards the 3T3 fibroblast cell line. The wound healing performance of AG/PVCL-TA was further confirmed in skin excision wound models, which demonstrated the potential application of AG/PVCL-TA for skin regeneration and rapid wound healing.

Green synthesis of zinc oxide nanoparticles from the leaf, stem and in vitro grown callus of Mussaenda frondosa L.: characterization and their applications.

Biosynthesis of zinc oxide nanoparticles (ZnO-NPs) was achieved by utilizing the reducing and capping potential of leaf, stem and callus aqueous extracts of Mussaenda frondosa.The bioreduced ZnO-NPs were characterized using powder X-ray diffraction (XRD), ultraviolet-visible spectroscopy (UV-Vis spectroscopy), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), fourier transform infrared spectroscopy (FTIR) and dynamic light scattering (DLS) techniques. UV-visible spectra of ZnO-NPs showed a strong absorption peak at 370, 376 and 373 nm corresponding to the band gap energy of 3.33, 3.27 and 3.30 eV for ZnO-NPs obtained from leaf (L-ZnO-NP), stem (S-ZnO-NP) and callus (C-ZnO-NP) aqueous extracts, respectively. XRD analysis confirmed the formation of hexagonal wurtzite structures having an average grain size between 5 and 20 nm in diameter. FTIR spectra revealed the presence of stretching vibrations of -O-H, C-H, C-N, C = O groups involved in reduction and stabilization of nanoparticles. SEM images recognize the presence of spongy, spherical, porous agglomerated nanoparticles. DLS analysis and zeta potential values validated the stability of ZnO-NPs. The present investigation puts light on the photocatalytic activity and biological (antioxidant, anti-inflammatory, antidiabetic, antimicrobial, anticancerous) applications of ZnO-NPs. The current study is an attempt to describe an effective, simple and eco-friendly method of ZnO-NP synthesis and to evaluate its potential for various industrial and medical applications.

Synthesis, In Vitro Anticancer, Anti-Inflammatory and DNA Binding Activity of Thiazolidinedione Derivatives.

BACKGROUND: Cancer is the second leading cause of mortality worldwide. Despite several advances made in the treatment strategies, the cure for cancer remains still a challenge. Currently used treatment modalities pose several side effects and remain ineffective in the later stages. Thiazolidinediones (TZDs) have been shown to possess anti-cancer activity in several in vitro models. OBJECTIVES: The objective of this study was to assess the effect of novel synthesized thiazolidinedione derivatives on three selected cancer cell lines viz., human breast adenocarcinoma cell line (MCF-7), lung adenocarcinoma (A549) and colorectal carcinoma (HT29). This study also aimed to evaluate the anti-inflammatory and DNA binding activity of the synthesized derivatives. METHODS: The synthesized thiazolidinedione derivatives were screened for their in vitro anti-cancer activity on the human breast adenocarcinoma cell line (MCF-7), lung adenocarcinoma (A549) and colorectal carcinoma (HT29) using the Methyl Thaizolyl Tetrazolium (MTT) Assay. They were also evaluated for in vitro antiinflammatory activity using albumin denaturation method, DNA binding activity and hemocompatibility. RESULTS: Compounds 5a, 5b, 5d, 6c and 6d showed IC50 of 30.19, 41.56, 65.97, 60.16 and 50.41µM respectively on breast adenocarcinoma (MCF-7), IC50 of 49.75, 51.42, 65.43, 61.94 and 56.80µM on lung adenocarcinoma (A549) and 38.11, 45.58, 71.24, 53.15 and 51.25µM on colorectal carcinoma (HT29). In the hemolysis assay, compounds 5a and 5b were found to be nontoxic and nonhemolytic to human erythrocytes. Five compounds possessed significant anticancer and anti-inflammatory activity. Three of them are Mannich bases, whereas the remaining two are aryl acyl derivatives. CONCLUSION: The in vitro results (anticancer and anti-inflammatory) showed that the 4-chloro anilinomethyl substitution at third position and thiophenoethenyl at the fifth position of thiozolidinedione (5a) emerged as the most effective derivative on all the tested cancer cell lines. A higher DNA binding affinity of the test compounds was also found.

Curcumin Suppresses Epithelial Growth Factor Receptor (EGFR) and Proliferative Protein (Ki 67) in Acute Lung Injury and Lung Fibrosis In vitro and In vivo.

BACKGROUND: Acute lung injury is one of the common conditions caused due to bleomycin therapy which leads to pulmonary fibrosis, which is one of the severe interstitial lung diseases most commonly affecting the elderly individuals. EGFR and Ki67 can be marked as beneficial markers for detecting pulmonary fibrosis based on which clinicians can guide the therapy. OBJECTIVE: The aim of the study was to evaluate the effect of curcumin as an intervention on two prognostic markers EGFR and Ki67 in bleomycin-induced basal alveolar epithelial cells and C57BL/6 mice. Protein expressions and pathological expressions of EGFR and Ki67 were evaluated to analyze the effect of curcumin via both in vitro and in vivo approaches. METHODS: The effect of curcumin was investigated both on cell lines (A549) and animal model (both normal and bleomycin-induced mice, n=6) via techniques like western blotting for protein expression. Techniques like immunofluorescence and immunohistochemistry were carried out and examined under confocal microscopy and phase contrast microscopy to analyze the expressions of the said biomarkers. Bleomycin was used as a causative agent to induce inflammation. RESULTS: The natural polyphenol curcumin could downregulate the expressions levels of Ki67 and EGFR both in vitro and in vivo. Immunofluorescence analysis of proliferative marker Ki67 showed a reduced expression on curcumin treatment in vitro. The pathological sections from treated lungs showed a significant decrease in EGFR and Ki67 levels when exposed to curcumin. CONCLUSION: We conclude that curcumin, a well-known natural bioactive compound holds strong antiproliferative effects on Ki67 and EGFR expressions.We observed that a clinical outcome in the diagnosis of pulmonary fibrosis remains to be unconvincing so far. Curcumin can be considered as a potential therapeutic.

Effect of calcium glucoheptonate on proliferation and osteogenesis of osteoblast-like cells in vitro.

Calcium is the key macromineral having a role in skeletal structure and function, muscle contraction, and neurotransmission. Bone remodeling is maintained through a constant balance between calcium resorption and deposition. Calcium deficiency is resolved through calcium supplementation, and among the supplements, water-soluble organic molecules attracted great pharmaceutical interest. Calcium glucoheptonate is a highly water-soluble organic calcium salt having clinical use; however, detailed investigations on its biological effects are limited. We assessed the effects of calcium glucoheptonate on cell viability and proliferation of osteoblast-like MG-63 cells. Calcium uptake and mineralization were evaluated using Alizarin red staining of osteoblast-like MG-63 cells treated with calcium glucoheptonate. Expression of osteogenic markers were monitored by western blotting, immunofluorescence, and qRT-PCR assays. Increased proliferation and calcium uptake were observed in the MG-63 cells treated with calcium glucoheptonate. The treatment also increased the expression of osteopontin and osteogenic genes such as collagen-1, secreted protein acidic and cysteine rich (SPARC), and osteocalcin. Calcium glucoheptonate treatment did not exert any cytotoxicity on colorectal and renal epithelial cells, indicating the safety of the treatment. This is the first report with evidence for its beneficial effect for pharmaceutical use in addressing calcium deficiency conditions.

Tetrandrine isolated from Cyclea peltata induces cytotoxicity and apoptosis through ROS and caspase pathways in breast and pancreatic cancer cells.

Tetrandrine is a bisbenzylisoquinoline alkaloid known to exhibit anticancer activity against different cancers. In the present study, the cytotoxic effect of tetrandrine isolated from Cyclea peltata on pancreatic (PANC-1) and breast (MDA-MB-231) cancer cells was evaluated in vitro with an attempt to understand the role of tetrandrine on the generation of reactive oxygen species (ROS) and caspase activation. Results demonstrate the dose- and time-dependant cytotoxic effect of tetradrine on both MDA-MB-231 and PANC-1 cells with IC50 values ranging between 51 and 54 µM and 22 and 27 µM for 24 h and 48 h of incubation respectively. In addition, treatment of MDA-MB-231 and PANC-1 cells with tetrandrine showed the shrunken cytoplasm and damaged cell membrane in a dose- and time-dependant manner under the microscope. Also, tetrandrine treatment revealed an elevated levels of reactive oxygen species and increased activities of caspase-8, -9 and -3 confirming the apoptosis of cells through both extrinsic death receptor and intrinsic caspase activation. Therefore, the present study suggests the apoptosis of cells with the activation of caspase pathways mainly intrinsic pathway as a downstream event of tetrandrine-induced ROS generation. Hence, reactive oxygen species-mediated caspase activation pathway may be potentially targeted with the use of tetrandrine to treat breast and pancreatic cancers.

Interleukin-17A: A Potential Therapeutic Target in Chronic Lung Diseases.

BACKGROUND: Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has gained a lot of attention because of its involvement in respiratory diseases. Interleukin-17 cytokine family includes six members, out of which, IL-17A participates towards the immune responses in allergy and inflammation. It also modulates the progression of respiratory disorders. OBJECTIVE: The present review is an insight into the involvement and contributions of the proinflammatory cytokine IL-17A in chronic respiratory diseases like Idiopathic Pulmonary Fibrosis (IPF), Chronic Obstructive Pulmonary Distress (COPD), asthma, pneumonia, obliterative bronchiolitis, lung cancer and many others. CONCLUSION: IL-17A is a major regulator of inflammatory responses. In all the mentioned diseases, IL- 17A plays a prime role in inducing the diseases, whereas the lack of this pro-inflammatory cytokine reduces the severity of respective respiratory diseases. Thereby, this review suggests IL-17A as an instrumental target in chronic respiratory diseases.