Factoring periodic maps into Dehn twists

Let $\text{Mod}(S_g)$ be the mapping class group of the closed orientable surface $S_g$ of genus $g \geq 1$. In this paper, we develop various methods for factoring periodic mapping classes into Dehn twists, up to conjugacy. As applications, we develop methods for factoring certain roots of Dehn twists as words in Dehn twists. We will also show the existence of conjugates of periodic maps of order $4g$ and $4g+2$, for $g\geq 2$, whose product is pseudo-Anosov

Nebulization based Inhalation Nanomedicine for Lung Cancer Treatments

Background: Lung cancer is reported to have a high incidence rate and first leading cause of cancer-related morbidity and mortality across the world including in the United States. Noninvasive nebulized inhalation is a promising delivery strategy for lung, which can enhance the targeting efficiency and detention time interval of nanoparticles in the lung tissue, thus elevating the therapeutic index of therapeutic agent(s) at lower dosages. The aim of this study is to develop inhalable nanoparticles (INPs) for effective delivery of therapeutic agents in lung cancer cell lines and ex vivo models. Methods: The inhalation nanoparticles (INPs) were prepared by solvent evaporation and self-assembly approach. The INPs formulations were characterized by particle size, chemical composition, and drug loading efficiency using various analytical methods including FT-IR, DSC, SEM, and DSC/TGA. Cellular uptake of INPs was evaluated in 2D and 3D models of lung cancer cell lines (A549 and NCI-H1299) using fluorescence microscopy and flow cytometry analysis. Additionally, the therapeutic evaluation of gambogic acid and gemcitabine encapsulated INPs was performed by basic in vitro biological assays using proliferation (CCK-8), mucoadhesion Boyden chamber, and apoptosis assays using lung cancer (A549 and NCI-H1299) monolayers, spheroids, and xenograft tumors. Results: The developed INPs exhibited an average size of ~110 nm in dynamic light scattering measurements. INPs formulation showed a remarkable mucoadhesion and mucopenetration potential in-vitro model(s). Cellular uptake studies demonstrated that INPs formulation facilitates an effective endosomal release into the cytosol. The in vitro study confirms that INPs release the drugs in a sustained manner. Additionally, the INPs formulation showed superior in vitro anti-cancer activity in lung cancer cell lines, spheroids and xenograft tumor. Conclusions: Altogether this study confirms that INPs formulation demonstrates an improved therapeutic benefit over free drug against lung cancer cell lines, spheroids and xenograft tumor. This study could lead as an innovative therapeutic modality for the treatment of lung cancer

A PORTRAYAL OF THE SOCIODEMOGRAPHICS AND OPTIMAL UPTAKE OF ANTENATALCARE SERVICES AMONG PREGNANT WOMEN OF URBAN SLUMS IN INDIA: AN INITIAL DATASET DEPICTION

Escalating deployment of maternal healthcare services has considerably impacted maternal mortality rates. However, urban slums have remained an understudied area in this context. Aim: To assess maternal healthcare service utilization patterns and influencing factors during antenatal period in urban slums. The analysis encompasses Fertility, Family Planning Practices, Dietary Habits, Health Quality, and implications of COVID-19 on Pregnancy. Method: Cross-sectional research conducted between April and June 2022, among urban slums in South Delhi, targeting pregnant women aged 18-44 years. Data from 250 ongoing pregnancies, accessed through Aganwadi centers, were collected electronically following study porotocol. Result: Results indicated that 98% of participants were under 40 years of age, with 67% falling below 28 years. About 93% of sample population was educated, with 93% as homemakers. Among women with parity, 82% had one child. Awareness of ANC was widespread, with 78% demonstrating medium level of knowledge. Media exposure and family planning adoption were minimal (47% and 51%, respectively). ANC utilization rates were high, with 98%, 97%, and 94% receiving iron and folic acid, tetanus toxoid, and ultrasound examinations, respectively. Only 2% were exposed to COVID-19 during pregnancy. Conclusion: This initial investigation indicates low media exposure and family planning adoption. However, ANC awareness and utilization were significant. Strategies should prioritize women's education to enhance awareness of ANC and postnatal care. Strengthening public health infrastructure is vital for optimizing maternal service utilization

Antifungal Drugs as Emerging Candidates for Prostate Cancer Treatment

Background: Prostate cancer remains a leading cause of cancer-related mortality in men, with approximately 299,010 new cases and 35,250 deaths projected in the United States in 2024. Despite advances in therapeutic options, including radiation, chemotherapy, hormone therapy, and biologics, significant long-term side effects challenge patient quality of life. Repurposing FDA-approved antifungal agents offers a novel approach to overcoming these limitations and can serve as a source of potential therapeutics against prostate cancer. Methods: This study evaluated the anticancer potential of antifungal drugs, such as natamycin, terbinafine, ketoconazole, clotrimazole, and miconazole, against prostate cancer cell lines. Cytotoxicity, colony formation, invasion, and migration assays were conducted to identify the most effective compound. The anticancer activity was assessed using confocal, scanning electron microscopy, and Western blotting. Gene expression profiling was performed by 3`m-RNA sequencing to investigate molecular pathways involved in apoptosis and stress responses. Results: Miconazole exhibited the most potent cytotoxic and clonogenic effects among the tested antifungal drugs on prostate cancer cell lines. A significant attenuation of cell migration and invasion was observed at 30 µM. Treatment-induced apoptosis was also evidenced by PARP cleavage and nuclear fragmentation. Ultrastructural morphology of cell images also revealed remarkable changes consistent with apoptosis features. The gene expression analysis demonstrated significantly upregulated key tumor suppressor or apoptotic genes and downregulated oncogenes, induced apoptosis, and ER stress in prostate cancer cell lines. Conclusions: These results demonstrate that miconazole exhibited the most anticancer potential against prostate cancer cells among the tested FDA-approved antifungal agents. While miconazole has been utilized clinically as an antifungal medication, its potential as a repurposed therapeutic agent for prostate cancer is a novel avenue and warrants further comprehensive investigation

Piperlongumine nanoformulation attenuates pancreatic tumor desmoplasia and alter tumor immune responses

Pancreatic cancer (PanCa) is characterized by lack of early diagnosis, poor response to available therapeutic modalities and chemoresistance. Gemcitabine (GEM) is currently considered the most effective therapy for PanCa; however, it shows only a marginal survival benefit of 6 months. This poor drug response has been attributed to desmoplasia, causes suboptimal drug delivery, alters tumor microenvironment (TME), which includes tumor surrounding blood vessels, fibroblasts, immune cells, extracellular matrix, and other signaling molecules and induces chemo-resistance in tumors. To overcome these existing issues associated with chemotherapy, identification and development of novel therapeutic modalities are a pressing need. Piperlongumine (PL) is a natural alkaloid isolated from the long pepper, Piper longum L., and has shown substantial cancer-preventive and therapeutic efficacy against a variety of cancers. However, delivering its effective concentration in pancreatic tumors has been challenging. We have recently engineered a multi-layered Pluronic F127 and polyvinyl alcohol stabilized, and poly-L-lysine coated piperlongumine loaded poly(lactic-co-glycolic acid) nanoparticle formulation (PLGA-PL), which effectively inhibits the growth of PanCa cells. In this study, we demonstrate that PLGA-PL effectively sensitizes tumor cells to GEM via decreased desmoplasia, altered TME, SHH/CXCL12/CXCR4 and immune surveillance. Our finding show that PLGA-PL synergizes with GEM in inhibiting PanCa cell (HPAF-II and Panc-1) growth, migration, and invasion compared to free PL. Mechanistically, PLGA-PL targets the TME via inhibition of sonic hedgehog (SHH) pathway and oncogenic CXCR4/CXCL12 signaling axis that inhibits bidirectional tumor-stromal cells interaction. We have also found that PLGA-PL alone and in combination with GEM targets cancer stem cells by inhibiting pluripotency maintaining stemness factors (Nanog, Sox2, c-Myc, CD133, and Oct-4) as determined by qRT-PCR, Western blotting, and immunofluorescence analysis, and further confirmed by restricting tumor sphere formation. Furthermore, PLGA-PL also effectively targets tumor-associated macrophages (TAM) by repolarizing M2 into M1 phenotype via inhibiting expression of M2 markers and an increase in M1 markers in mouse macrophage cell line RAW264.7. M2 polarization of RAW264.7 cells were induced by culture with IL-4 (20 ng/mL) in presence of PLGA-PL or vehicle control. In addition, PLGA-PL effectively increases phagocytic capacity in murine macrophages as determined by phagocytosis assay (Vybrant Phagocytosis Assay Kit). In conclusion, we observed that PLGA-PL effectively targets TME, facilitates GEM uptake by inhibiting the activation of CXCR4/CXCL12/SHH signaling, and reprograming the tumor immune surveillance. This study suggests that PLGA-PL has great potential for future clinical use in management of PanCa

Novel nanoformulation of piperlongumine attenuates pancreatic tumor desmoplasia and modulates tumor immune responses

Pancreatic cancer (PanCa) is characterized by a lack of early diagnosis, poor response to available therapeutic modalities, and chemoresistance. Gemcitabine (GEM) is currently considered the most effective therapy for PanCa; however, it shows only a marginal survival benefit of 6 months. This poor drug response has been attributed to desmoplasia, causes suboptimal drug delivery, alters tumor microenvironment (TME), which includes tumor surrounding blood vessels, fibroblasts, immune cells, extracellular matrix, and other signaling molecules and induces chemo-resistance in tumors. To overcome these existing issues associated with chemotherapy, the identification and development of novel therapeutic modalities are a pressing need. Piperlongumine (PL) is a natural alkaloid isolated from the long pepper, Piper longum L., and has shown substantial cancer-preventive and therapeutic efficacy against various cancers. However, delivering its effective concentration in pancreatic tumors has been challenging. We have recently engineered a multi-layered Pluronic F127 and polyvinyl alcohol stabilized, and poly-L-lysine coated piperlongumine loaded poly(lactic-co-glycolic acid) nanoparticle formulation (PLGA-PL), which effectively inhibits the growth of PanCa cells. This study demonstrates that PLGA-PL effectively sensitizes tumor cells to GEM via decreased desmoplasia, altered TME, SHH/CXCL12/CXCR4, and immune surveillance. Our findings show that PLGA-PL synergizes with GEM in inhibiting PanCa cell (HPAF-II and Panc-1) growth, migration, and invasion compared to free PL. Mechanistically, PLGA-PL targets the TME by inhibiting the sonic hedgehog (SHH) pathway and oncogenic CXCR4/CXCL12 signaling axis that inhibits bidirectional tumor-stromal cell interaction. We have also found that PLGA-PL alone and in combination with GEM targets cancer stem cells by inhibiting pluripotency maintaining stemness factors (Nanog, Sox2, c-Myc, CD133, and Oct-4) as determined by qRT-PCR, Western blotting, and immunofluorescence analysis, and further confirmed by restricting tumor sphere formation. Furthermore, PLGA-PL also effectively targets tumor-associated macrophages (TAM) by repolarizing M2 into M1 phenotype via inhibiting the expression of M2 markers and an increase in M1 markers in mouse macrophage cell line RAW264.7. M2 polarization of RAW264.7 cells was induced by culture with IL-4 (20 ng/mL) in the presence of PLGA-PL or vehicle control. In addition, PLGA-PL effectively increases phagocytic capacity in murine macrophages as determined by phagocytosis assay (Vybrant Phagocytosis Assay Kit). In conclusion, we observed that PLGA-PL effectively targets TME and facilitates GEM uptake by inhibiting the activation of CXCR4/CXCL12/SHH signaling and reprograming tumor immune surveillance. This study suggests that PLGA-PL has great potential for future clinical use in the management of PanCa