Search

Groundwater recharge is essential for managing surface and subsoil water resources. Not only for supplying people with daily drinking water, groundwater use for agricultural land and people's livelihood is also continuously increasing. As a result, there has been a decline in groundwater supply in various parts of the world, and it is highly desirable to identify the potential groundwater zones for specific sustainable development. This study aims to use an easy-to-use tool package named Landslide Sustainability Mapping Tool pack (LSM tool Pack) for preparing potential groundwater zone based on R and ArcGIS software integration. This tool uses five modules for processing. Among them, the Feature selection (FS) module brings a novel approach, determining the best subset feature for demarcating the groundwater potential zone. As a result, this best factor subset is used as an input of this tool pack. Additionally, PE modules evaluate the performance of proposed models in statistical performance metrics. In addition, the receiver operating characteristic (ROC) curve was obtained with the integration of Performance Evaluation (PE) modules and ARC maps, which helps visual interpretation in evaluating models. This study uses the LSM tool Pack in the Rupnarayan river basin to map the potential groundwater zone based on fourteen controlling factors selected through the FS module, which will further help the local government to make a substitute policy. [ABSTRACT FROM AUTHOR]

Development of fluorescent imaging probes is an important topic of research for the early diagnosis of cancer. Based on the difference between the cellular environment of tumor cells and normal cells, several "smart" fluorescent probes have been developed. In this work, a glycopolymer functionalized Förster resonance energy transfer (FRET) based fluorescent sensor is developed, which can monitor the pH change in cellular system. One‐pot sequential reversible addition‐fragmentation chain transfer (RAFT)polymerization technique is employed to synthesize fluorescent active triblock glycopolymer that can undergo FRET change on the variation of pH. A FRET pair, fluorescein o‐acrylate (FA) and 7‐amino‐4‐methylcoumarin (AMC) is linked via a pH‐responsive polymer poly [2‐(diisopropylamino)ethyl methacrylate] (PDPAEMA), which can undergo reversible swelling/deswelling under acidic/neutral condition. The presence of glycopolymer segment provides stability, water solubility, and specificity toward cancer cells. The cellular FRET experiments on cancer cells (MDA MB 231) and normal cells (3T3 fibroblast cells) demonstrate that the material is capable of distinguishing cells as a function of pH change. [ABSTRACT FROM AUTHOR]

Temozolomide (TMZ) is the leading chemotherapeutic agent used for glioma therapy due to its good oral absorption and blood-brain barrier permeability. However, its anti-glioma efficacy may be limited due to its adverse effects and resistance development. O6-Methylguanine-DNA-methyltransferase (MGMT), an enzyme associated with TMZ resistance, is activated via the NF-κB pathway, which is found to be upregulated in glioma. TMZ also upregulates NF-κB signaling like many other alkylating agents. Magnolol (MGN), a natural anti-cancer agent, has been reported to inhibit NF-κB signaling in multiple myeloma, cholangiocarcinoma, and hepatocellular carcinoma. MGN has already shown promising results in anti-glioma therapy. However, the synergistic action of TMZ and MGN has not been explored. Therefore, we investigated the effect of TMZ and MGN treatment in glioma and observed their synergistic pro-apoptotic action in both in vitro and in vivo glioma models. To explore the mechanism of this synergistic action, we found that MGN inhibits MGMT enzyme both in vitro and in vivo glioma. Next, we established the link between NF-κB signaling and MGN-induced MGMT inhibition in glioma. MGN inhibits the phosphorylation of p65, a subunit of NF-κB, and its nuclear translocation to block NF-κB pathway activation in glioma. MGN-induced NF-κB inhibition results in the transcriptional inhibition of MGMT in glioma. TMZ and MGN combinatorial treatment also impedes p65 nuclear translocation to inhibit MGMT in glioma. We observed a similar effect of TMZ and MGN treatment in the rodent glioma model. Thus, we concluded that MGN potentiates TMZ-induced apoptosis in glioma by inhibiting NF-κB pathway-mediated MGMT activation. [Display omitted] • Magnolol potentiates the anti-glioma efficacy of Temozolomide. • Magnolol inactivates NF-κB pathway by blocking p65 nuclear translocation and inhibits MGMT in glioma. • Magnolol and Temozolomide exert synergistic apoptosis in glioma due to MGMT inhibition by Magnolol. [ABSTRACT FROM AUTHOR]

We report a two-photon responsive drug delivery system (DDS), namely, p-hydroxyphenacyl–naphthalene–chlorambucil (pHP–Naph–Cbl), having a two-photon absorption (TPA) cross-section of ≥20 GM in the phototherapeutic window (700 nm). Our DDS exhibited both AIE and ESIPT phenomena, which were utilized for the real-time monitoring of anti-cancer drug release. [ABSTRACT FROM AUTHOR]

In this work, we depleted glutathione (GSH) by releasing SO2 with internal stimulus GSH itself, and also selectively marked the cancer cells followed by release of anticancer drug using another orthogonal stimulus i.e., two-photon (TP) NIR light by a single naphthalene based chromophore (TP absorbance 77 GM and uncaging cross-section 21 GM). We demonstrated the improved therapeutic efficacy of chlorambucil by the stepwise dual stimuli approach and dual surveillance of both the drug uncaging process in real-time using in vitro studies. [ABSTRACT FROM AUTHOR]

Chemoresistance is a primary cause of breast cancer treatment failure, and protein-protein interactions significantly contribute to chemoresistance during different stages of breast cancer progression. In pursuit of novel biomarkers and relevant protein-protein interactions occurring during the emergence of breast cancer chemoresistance, we used a computational predictive biological (CPB) approach. CPB identified associations of adhesion molecules with proteins connected with different breast cancer proteins associated with chemoresistance. This approach identified an association of Integrin β1 (ITGB1) with chemoresistance and breast cancer stem cell markers. ITGB1 activated the Focal Adhesion Kinase (FAK) pathway promoting invasion, migration, and chemoresistance in breast cancer by upregulating Erk phosphorylation. FAK also activated Wnt/Sox2 signaling, which enhanced self-renewal in breast cancer. Activation of the FAK pathway by ITGB1 represents a novel mechanism linked to breast cancer chemoresistance, which may lead to novel therapies capable of blocking breast cancer progression by intervening in ITGB1-regulated signaling pathways. [Display omitted] • Developed a novel Computational-Predictive-Biological (CPB) strategy to predict different types of biomarkers in cancers. • CBP identified that ITGB1 is associated with chemoresistance, and cancer stem cell associated proteins in breast cancer. • ITGB1 regulated chemoresistance via activation of FAK pathway which regulates survival pathways, invasion, migration. • ITGB1 also regulated activated Wnt/Sox2 signaling through FAK, which enhanced self-renewal in breast cancer. • Thus, CBP established a unified pathway to regulate chemoresistance in breast cancer and ITGB1 as a potential biomarker. [ABSTRACT FROM AUTHOR]

Background: Endodontic microbial flora plays a pivotal role in the development and persistence of periodontal endodontic lesions (PELs). Understanding the composition and prevalence of microbial species in PELs is essential for effective treatment strategies. Materials and Methods: Microbial samples were collected from 50 teeth diagnosed with PELs. Sterile paper points were used to obtain samples from the root canals. Deoxyribonucleic acid (DNA) was extracted and subjected to polymerase chain reaction (PCR) amplification of the 16S ribosomal RNA (rRNA) gene to identify bacterial species. The obtained data were analyzed using statistical methods. Results: The microbial analysis revealed a diverse range of bacterial species in PELs. The most prevalent species were Porphyromonas gingivalis (32.5%), Treponema denticola (28.0%), and Fusobacterium nucleatum (22.5%). Streptococcus mutans (9.0%) and Actinomyces naeslundii (8.0%) were also frequently detected. Additionally, Prevotella intermedia (7.0%), Aggregatibacter actinomycetemcomitans (3.5%), and Enterococcus faecalis (2.5%) were present in lower frequencies. Conclusion: The presence of a diverse microbial flora in teeth with PELs underscores the polymicrobial nature of these lesions. The predominance of periodontal pathogens such as Porphyromonas gingivalis, Treponema denticola, and Fusobacterium nucleatum suggests a strong association between periodontal and endodontic infections. A comprehensive understanding of the microbial profile in PELs is crucial for tailored therapeutic approaches targeting the specific pathogens involved. [ABSTRACT FROM AUTHOR]

Glioma is difficult-to-treat because of its infiltrative nature and the presence of the blood-brain barrier. Temozolomide is the only FDA-approved drug for its management. Therefore, finding a novel chemotherapeutic agent for glioma is of utmost importance. Magnolol, a neolignan, has been known for its apoptotic role in glioma. In this work, we have explored a novel anti-glioma mechanism of Magnolol associated with its role in autophagy modulation. We found increased expression levels of Beclin-1, Atg5-Atg12, and LC3-II and lower p62 expression in Magnolol-treated glioma cells. PI3K/AKT/mTOR pathway proteins were also downregulated in Magnolol-treated glioma cells. Next, we treated the glioma cells with Insulin, a stimulator of PI3K/AKT/mTOR signaling, to confirm that Magnolol induced autophagy by inhibiting this pathway. Insulin reversed the effect on Magnolol-mediated autophagy induction. We also established the same in in vivo glioma model where Magnolol showed an anti-glioma effect by inducing autophagy. To confirm the cytotoxic effect of Magnolol-induced autophagy, we used Chloroquine, a late-stage autophagy inhibitor. Chloroquine efficiently reversed the anti-glioma effects of Magnolol both in vitro and in vivo. Our study revealed the cytotoxic effect of Magnolol-induced autophagy in glioma, which was not previously reported. Additionally, Magnolol showed no toxicity in non-cancerous cell lines as well as rat organs. Thus, we concluded that Magnolol is an excellent candidate for developing new therapeutic strategies for glioma management. [Display omitted] • Magnolol causes no toxicity in rat organs. • Magnolol induces autophagy in glioma by inhibiting PI3K/AKT/mTOR signaling. • Magnolol causes cytotoxic autophagy in glioma. [ABSTRACT FROM AUTHOR]

Sox family of transcriptional factors play essential functions in development and are implicated in multiple clinical disorders, including cancer. Sox2 being their most prominent member and performing a critical role in reprogramming differentiated adult cells to an embryonic phenotype is frequently upregulated in multiple cancers. High Sox2 levels are detected in breast tumor tissues and correlate with a worse prognosis. In addition, Sox2 expression is connected with resistance to conventional anticancer therapy. Together, it can be said that inhibiting Sox2 expression can reduce the malignant features associated with breast cancer, including invasion, migration, proliferation, stemness, and chemoresistance. This review highlights the critical roles played by the Sox gene family members in initiating or suppressing breast tumor development, while primarily focusing on Sox2 and its role in breast tumor initiation, maintenance, and progression, elucidates the probable mechanisms that control its activity, and puts forward potential therapeutic strategies to inhibit its expression. [ABSTRACT FROM AUTHOR]

Prostate cancer, one of the most frequently occurring cancers in men, is a heterogeneous disease involving multiple cell types within tumors. This tumor heterogeneity at least partly results from genomic instability leading to sub-clonal cellular differentiation. The differentiated cell populations originate from a small subset of cells with tumor-initiating and stem-like properties. These cells, termed prostate cancer stem cells (PCSCs), play crucial roles in disease progression, drug resistance, and relapse. This review discusses the origin, hierarchy, and plasticity of PCSCs; methods for isolation and enrichment of PCSCs; and various cellular and metabolic signaling pathways involved in PCSC induction and maintenance, as well as therapeutic targeting. [ABSTRACT FROM AUTHOR]

In this study, a polyhedral oligomeric silsesquioxane-polycaprolactone (POSS-PCL)-cored octa-arm star-shaped glyco block copolymer (BCP), poly(ε-caprolactone)- b -poly(glucopyranose) (Star -POSS-PCL- b -PGlc) was successfully synthesized via the combination of ring opening polymerization (ROP) and MADIX (macromolecular design by interchange of xanthate) polymerization technique. Herein, initially octa(3-hydroxy-3-methylbutyl dimethylsiloxy) POSS (Star -POSS) was utilized to initiate the ROP of the ε-caprolactone to get octa-arm star-shaped Star -POSS-PCL. A successive bromination followed by xanthation of the synthesized Star -POSS-PCL polymer allowed us to further polymerize 3-O-acryloyl-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (AIpGlc) via MADIX polymerization. Formation of the star-shaped block copolymer (BCP) was characterized using 1H NMR, FT-IR and DSC analyses. The morphology and the aqueous solution behavior of the St ar-POSS-PCL- b -PGlc were analyzed using FESEM, HRTEM and DLS analyses, respectively. The lectin-binding efficiency of the star-shaped BCP having different glycopolymer block length was studied using turbidimetry assay and fluorescence quenching titration (FQT) using photoluminescence spectroscopy (PL). Here, FITC labeled concanavalin A (FITC-Con A) was used as a model lectin. The cytotoxicity study of the star-shaped BCPs over the human fibroblast cells revealed the non-toxic nature of the BCPs which open up its great potential towards drug delivery vector. Unlabelled Image [ABSTRACT FROM AUTHOR]

The Transforming growth factor-β1 (TGF- β1) in the tumor microenvironment (TME) is the major cytokine that acts as a mediator of tumor-stroma crosstalk, which in fact has a dual role in either promoting or suppressing tumor development. The cancer-associated fibroblasts (CAFs) are the major cell types in the TME, and the interaction with most of the epithelial cancers is the prime reason for cancer survival. However, the molecular mechanisms, associated with the TGF- β1 induced tumor promotion through tumor-CAF crosstalk are not well understood. In the Reverse Warburg effect, CAFs feed the adjacent cancer cells by lactate produced during the aerobic glycolysis. We hypothesized that the monocarboxylate transporter, MCT4 which is implicated in lactate efflux from the CAFs, must be overexpressed in the CAFs. Contextually, to explore the role of TGF- β1 in the hypoxia-induced autophagy in CAFs, we treated CoCl 2 and external TGF- β1 to the human dermal fibroblasts and L929 murine fibroblasts. We demonstrated that hypoxia accelerated the TGF- β1 signaling and subsequent transformation of normal fibroblasts to CAFs. Moreover, we elucidated that synergistic induction of autophagy by hypoxia and TGF- β1 upregulate the aerobic glycolysis and MCT4 expression in CAFs. Furthermore, we showed a positive correlation between glucose consumption and MCT4 expression in the CAFs. Autophagy was also found to be involved in the EMT in hypoxic CAFs. Collectively, these findings reveal the unappreciated role of autophagy in TME, which enhances the CAF transformation and that promotes tumor migration and metastasis via the reverse Warburg effect. [Display omitted] • The crosstalk between the tumor and CAFs via TGF-β1 promotes tumor progression. • TGF-β1 from the tumors induces the transformation of normal fibroblast to CAFs. • Synergistically, TGF-β1, and hypoxia induce autophagy in the CAFs. • CAFs metabolically support tumor growth via lactate production and MCT4 upregulation. [ABSTRACT FROM AUTHOR]

• A thermoresponsive and self-healable multi-layered micellar interpolyelectolyte complex (IPEC) hydrogel has been prepared. • IPEC hydrogel consists of ionic block copolymers (BCPs), prepared via RAFT polymerization. • Ag NPs embedded thermogel showed wound healing activity studied over Wistar rats (in vivo study). • qRT-PCR and IHC study approved the tissue inflammation and angiogenic potential (wound healing activity) of the thermogel. • Ag NPs embedded thermogel showed antimicrobial activity against both Gram-positive and Gram-negative bacteria. There have been great interests in the development of new smart materials for the wound-healing application. Herein, we have designed a new wound-healable material based on thermoresponsive multi-layered micellar interpolyelectolyte complex (IPEC) hydrogel. The polyelectrolyte BCPs were prepared via reversible addition-fragmentation chain-transfer (RAFT) polymerization. The combination of inner thiolated cationic poly(2-hydroxyethyl methacrylate- block -(2-(methacryloyloxy)ethyltrimethyl ammonium chloride) (PHEMA -b- PMTAC) BCP stabilized Ag NPs and outer anionic thermoresponsive poly(N-isopropylacrylamide- block -sodium 4-vinylbenzenesulfonate) (PNIPAAm -b- PSS) BCP moiety of the IPEC provides self-healing property to the complex via ionic interaction. The morphology of the resulting IPEC was investigated by FESEM, AFM, and HRTEM analyses. The spray-on thermoresonsive IPEC was found to form self-standing hydrogel at the wound site above its lower critical solution temperature (LCST at 33 °C), as determined using temperature-responsive DLS analysis. The Ag NPs embedded hydrogel showed a catastrophic effect against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria which was confirmed using Live-dead assay (DAPI-PI analysis), flow cytometry (FACS) study and morphological analyses. This ensures the prevention of wound infection. Upon application of this Ag NPs embedded IPEC in the wound site of Wistar rats (in vivo study), the re-epithelialization process was observed to be facilitated leading to wound healing. The CD31 and Collagen IV markers were used in the immunohistochemistry (IHC) study of the wound closure process. The combination of the qRT-PCR and IHC study suggested that the Ag NPs incorporated thermogel can have application as anti-flammation and angiogenic material. The multifunctional activities of this new IPEC based hydrogel can shed light in the field of wound dressing application. [ABSTRACT FROM AUTHOR]