Sustainable Sensing with Paper Microfluidics: Applications in Health, Environment, and Food Safety.

This manuscript offers a concise overview of paper microfluidics, emphasizing its sustainable sensing applications in healthcare, environmental monitoring, and food safety. Researchers have developed innovative sensing platforms for detecting pathogens, pollutants, and contaminants by leveraging the paper's unique properties, such as biodegradability and affordability. These portable, low-cost sensors facilitate rapid diagnostics and on-site analysis, making them invaluable tools for resource-limited settings. This review discusses the fabrication techniques, principles, and applications of paper microfluidics, showcasing its potential to address pressing challenges and enhance human health and environmental sustainability.

Organic Electronics in Biosensing: A Promising Frontier for Medical and Environmental Applications.

The promising field of organic electronics has ushered in a new era of biosensing technology, thus offering a promising frontier for applications in both medical diagnostics and environmental monitoring. This review paper provides a comprehensive overview of organic electronics' remarkable progress and potential in biosensing applications. It explores the multifaceted aspects of organic materials and devices, thereby highlighting their unique advantages, such as flexibility, biocompatibility, and low-cost fabrication. The paper delves into the diverse range of biosensors enabled by organic electronics, including electrochemical, optical, piezoelectric, and thermal sensors, thus showcasing their versatility in detecting biomolecules, pathogens, and environmental pollutants. Furthermore, integrating organic biosensors into wearable devices and the Internet of Things (IoT) ecosystem is discussed, wherein they offer real-time, remote, and personalized monitoring solutions. The review also addresses the current challenges and future prospects of organic biosensing, thus emphasizing the potential for breakthroughs in personalized medicine, environmental sustainability, and the advancement of human health and well-being.

Chemokines and cytokines: Axis and allies in prostate cancer pathogenesis.

Chemokines are recognized as the major contributor to various tumorigenesis, tumor heterogeneity, and failures of current cancer therapies. The tumor microenvironment (TME) is enriched with chemokines and cytokines and plays a pivotal role in cancer progression. Chronic inflammation is also considered an instructive process of cancer progression, where chemokines are spatiotemporally secreted by malignant cells and leukocyte subtypes that initiate cell trafficking into the TME. In various cancers, prostate cancer (PCa) is reported as one of the leading cancers in the worldwide male population. The chemokines-mediated signaling pathways are intensively involved in PCa progression and metastasis. Emerging evidence suggests that chemokines and cytokines are responsible for the pleiotropic actions in cancer, including the growth, angiogenesis, endothelial mesenchymal transition, leukocyte infiltration, and hormone escape for advanced PCa and therapy resistance. Chemokine's system and immune cells represent a promising target to suppress tumorigenic environments and serve as potential therapy/immunotherapy for the PCa. In this review, an attempt has been made to shed light on the alteration of chemokine and cytokine profiles during PCa progression and metastasis. We also discussed the recent findings of the diverse molecular signaling of these circulating chemokines and their corresponding receptors that could become future targets for therapeutic management of PCa.

Microtubule depolymerization attenuates WNT4/CaMKIIα signaling in mouse uterus and leads to implantation failure.

Microtubule (MT) dynamics plays a crucial role in fertilization and early embryonic development; however its involvement in uterus during embryo implantation remains unclear. Herein, we report the effect of microtubule depolymerization during embryo implantation in BALB/c mice. Intrauterine treatment with depolymerizing agent nocodazole at pre-implantation phase (D4, 07:00 h) in mice resulted into mitigation in receptivity markers viz. LIF, HoxA10, Integrin-ß3, IHH, WNT4 and led to pregnancy failure. MT depolymerization in endometrial epithelial cells (EECs) also inhibited the blastocyst attachment and the adhesion. The decreased expression of MT polymerization-related proteins TPPP and α/ß-tubulin in luminal and glandular epithelial cells along with the alteration in morphology of pinopodes in the luminal epithelium was observed in nocodazole receiving uteri. Nocodazole treatment also led to increased intracellular Ca+2 levels in EECs, which indicated that altered Ca+2 homeostasis might be responsible for implantation failure. Microtubule depolymerization inhibited WNT4 and Fz-2 interaction, thereby suppressing the downstream WNT4/CaMKIIα signaling cascades calmodulin and calcineurin which led to attenuation of NF-κB transcriptional promoter activity in EECs. MT depolymerization or CaMKIIα knockdown inhibited the transcription factor NFAT and NF-κB expression along with reduced secretion of prostaglandins PGE2 and PGF2α in mouse EECs. Overall, MT depolymerization impaired the WNT4/CaMKIIα signaling and suppressed the secretion of PGE2 and PGF2α in EECs which may be responsible for implantation failure in mice.

Inhibition of TPPP3 attenuates ß-catenin/NF-κB/COX-2 signaling in endometrial stromal cells and impairs decidualization.

Embryo implantation and decidualization are critical events that occur during early pregnancy. Decidualization is synchronized by the crosstalk of progesterone and the cAMP signaling pathway. Previously, we confirmed the role of TPPP3 during embryo implantation in mice, but the underlying role and mechanism of TPPP3 in decidualization has not yet been understood. The current study was aimed to investigate the role of TPPP3 in decidualization in vivo and in vitro. For in vivo experiments, decidual reaction was artificially induced in the uteri of BALB/c mice. TPPP3 was found to be highly expressed during decidualization, whereas in the uteri receiving TPPP3 siRNA, decidualization was suppressed and the expression of ß-catenin and decidual marker prolactin was reduced. In human endometrium, TPPP3 protein was found to be predominantly expressed in the mid-secretory phase (LH+7). In the primary culture of human endometrial stromal cells (hESCs), TPPP3 siRNA knockdown inhibited stromal-to-decidual cell transition and decreased the expression of the decidualization markers prolactin and IGFBP-1. Immunofluorescence and immunoblotting experiments revealed that TPPP3 siRNA knockdown suppressed the expression of ß-catenin, NF-κB and COX-2 in hESCs during decidualization. TPPP3 inhibition also decreased NF-kB nuclear accumulation in hESCs and suppressed NF-κB transcriptional promoter activity. COX-2 expression was significantly decreased in the presence of a selective NF-kB inhibitor (QNZ) implicating that NF-kB is involved in COX-2 expression in hESCs undergoing decidualization. TUNEL assay and FACS analysis revealed that TPPP3 knockdown induced apoptosis and caused loss of mitochondrial membrane potential in hESCs. The study suggested that TPPP3 plays a significant role in decidualization and its inhibition leads to the suppression of ß-catenin/NF-κB/COX-2 signaling along with the induction of mitochondria-dependent apoptosis.

Uterine TPPP3 plays important role in embryo implantation via modulation of ß-catenin.

Tubulin polymerization promoting protein 3 (TPPP3) is known to be expressed in the endometrium in a cyclic manner, and its functional role in the physiology of implantation remains unknown. Here we demonstrate a novel function of TPPP3 during the window of implantation and in the establishment of pregnancy using a mouse model. The increased protein expression of TPPP3 and ß-catenin during peri-implantation period, i.e. D5 (receptive phase, 0800 h), was observed as compared to that on D1 (nonreceptive phase, 0800 h). SiRNATPPP3-mediated knockdown of uterine TPPP3 resulted in implantation failure and inhibited the expression of receptivity markers: LIF, Integrin-ß3, IHH, and Wnt4. TPPP3 silencing in mouse endometrial epithelial cells also prevented blastocyst attachment and the adhesion reaction. In delayed implantation experiment, expression of TPPP3 was increased in active implantation group (E2 + P4) compared to delayed implantation group (P4). The increased expression of TPPP3 in E2 + P4-treated Ishikawa cells compared to vehicle or P4 or E2 alone-treated Ishikawa cells also revealed its upregulation by E2. The suppression of ß-catenin in uterus under the condition of transient knockdown of TPPP3 and the co-immunoprecipitation experiment revealed that regulation of ß-catenin was mediated via TPPP3 during implantation. Additionally, in order to gain insight into TPPP3 collaborators, we identified TPPP3 interacting proteins by nanoLC-MS analysis in mouse uterus which might be involved during implantation. In conclusion, our study suggests that TPPP3 is important for embryo implantation and for the establishment of early pregnancy through modulation of ß-catenin.

The regulation of Hh/Gli1 signaling cascade involves Gsk3ß- mediated mechanism in estrogen-derived endometrial hyperplasia.

The present study was undertaken to explore the functional involvement of Hh signaling and its regulatory mechanism in endometrial hyperplasia. Differential expression of Hh signaling molecules i.e., Ihh, Shh, Gli1 or Gsk3ß was observed in endometrial hyperplasial (EH) cells as compared to normal endometrial cells. Estradiol induced the expression of Hh signaling molecules and attenuated the expression of Gsk3ß whereas anti-estrogen (K1) or progestin (MPA) suppressed these effects in EH cells. Cyclopamine treatment or Gli1 siRNA knockdown suppressed the growth of EH cells and reduced the expression of proliferative markers. Estradiol also induced the nuclear translocation of Gli1 which was suppressed by both MPA and K1 in EH cells. While exploring non-canonical mechanism, LY-294002 (Gsk3ß activator) caused a decrease in Gli1 expression indicating the involvement of Gsk3ß in Gli1 regulation. Further, Gsk3ß silencing promoted the expression and nuclear translocation of Gli1 demonstrating that Gsk3ß serves as a negative kinase regulator of Gli1 in EH cells. Similar attenuation of Hh signaling molecules was observed in rats with uterine hyperplasia undergoing anti-estrogen treatment. The study suggested that Hh/Gli1 cascade (canonical pathway) as well as Gsk3ß-Gli1 crosstalk (non-canonical pathway) play crucial role in estrogen-dependent cell proliferation in endometrial hyperplasia.

Curcumin exhibits anti-tumor effect and attenuates cellular migration via Slit-2 mediated down-regulation of SDF-1 and CXCR4 in endometrial adenocarcinoma cells.

Although curcumin shows anti-proliferative and anti-inflammatory activities in various cancers, the effect of curcumin on cellular migration in endometrial adenocarcinoma cells remains to be understood. The current investigation was aimed to explore the anti-proliferative and anti-migratory effects of curcumin and its mechanism of action in endometrial cancer cells. Our in-vitro and in-vivo experimental studies showed that curcumin inhibited the proliferation of endometrial cancer cells and suppressed the tumor growth in Ishikawa xenograft mouse model. Curcumin induced ROS-mediated apoptosis in endometrial cancer cells. Curcumin suppressed the migration rate of Ishikawa and Hec-1B cells as analyzed by scratch wound assay. In transwell migration studies, knock down of Slit-2 reversed the anti-migratory effect of curcumin in these cell lines. Curcumin significantly up-regulated the expression of Slit-2 in Ishikawa, Hec-1B and primary endometrial cancer cells while it down-regulated the expression of stromal cell-derived factor-1 (SDF-1) and CXCR4 which in turn, suppressed the expression of matrix metallopeptidases (MMP) 2 and 9, thus attenuating the migration of endometrial cancer cells. In summary, we have demonstrated that curcumin has inhibitory effect on cellular migration via Slit-2 mediated down-regulation of CXCR4, SDF-1, and MMP2/MMP9 in endometrial carcinoma cells. These findings helped explore the role of Slit-2 in endometrial cancer cells.

Regulation of cyclooxygenase-2 expression in rat oviductal epithelial cells: Evidence for involvement of GPR30/Src kinase-mediated EGFR signaling.

The oviduct plays a crucial role in female reproduction by regulating gamete transport, providing a specific microenvironment for fertilization and early embryonic development. Cyclooxygenase (COX)-derived prostaglandins play essential role in carrying out these oviduct-specific functions. Estrogen upregulates COX-2 expression in rat oviduct; however, the mechanisms responsible for regulation of COX-2 expression in rat oviductal epithelial cells (OECs) remain unclear. In the present study, we proposed that estrogen induces COX-2 expression via G-protein coupled receptor i.e., GPR30 in OECs. To investigate this hypothesis, we examined the effects of E2-BSA, ICI 182,780, GPR30 agonist and GPR30 antagonist on COX-2 expression and explored potential signaling pathway leading to COX-2 expression. Co-localization experiments revealed GPR30 to be primarily located in the peri-nuclear space, which was also the site of E2-BSA-fluorescein isothiocyanate (E2-BSA-FITC) binding. The E2-BSA induced-COX-2 and prostaglandin release were subjected to regulation by both EGFR and PI3K signaling as inhibitors of c-Src kinase (PP2), EGFR (EGFR inhibitor) and PI-3 kinase (LY294002) attenuated E2-BSA mediated effect. These results suggest that EGFR transactivation leading to activation of PI-3K/Akt pathway participates in COX-2 expression in rat OECs. Interestingly, E2-BSA induced COX-2 expression and subsequent prostaglandin release were abolished by NF-κB inhibitor. In addition, E2-BSA induced the nuclear translocation of p65-NF-κB and up-regulated the NF-κB promoter activity in rat OECs. Taken together, results demonstrated that E2-BSA induced the COX-2 expression and consequent PGE2 and PGF2α release in rat OECs. These effects are mediated through GPR30-derived EGFR transactivation and PI-3K/Akt cascade leading to NF-κB activation.