Spectrum of fireworks related ocular injuries on the day of Deepavali

Fireworks are often associated with severe ocular injury. In India, fireworks are an important cause of ocular injury during Deepavali festival. We present the spectrum of fire-cracker related ocular injuries on the day of Deepavali and their associated risk factors. All patients with cracker related ocular injuries on Deepavali day, seen at a tertiary care eye hospital, are included in this case series. This case series evaluates the type of ocular injury, type of firecracker involved and the associated risk factors leading to the casualtie

Studying the molecular mechanism of hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) has a poor prognosis due to ineffective therapeutic modality and lack of early diagnostic marker. Accumulating studies have shown that elevated expression of mucin 13 as potential oncogene and predictive biomarker for various cancer. However, very little is known about its expression and function for development and progression of HCC. Objective: To investigate mucin 13 expression in chemically induced hepatocellular carcinoma model. Methodology: Diethyl nitrosamine (DEN) and 2-Acetylaminofluorene (2-AAF) induced method was employed for the development of hepatocellular carcinoma in Male Wistar rats. Serum and tissues were collected at regular intervals of time and routinely validated for liver cancer stages. Immunohistochemistry and in situ hybridization were performed on formalin-fixed, paraffin-embedded tissues. Molecular docking studies were performed to study the interaction of mucin 13 and DEN. Results: Our results demonstrate hepatocellular adenoma as observed by histopathological analysis. Biochemical analysis showed a progressive increase in the levels of serum ALT, AST, and ALP, suggesting the development and progression of hepatocellular damage. Notably, mucin 13 expression gradually elevated during consecutive stages of hepatocellular carcinoma. Interestingly, an increase in nuclear localization of mucin 13 was observed in the treated group as compared to control group. In situ hybridization analysis showed that a decrease in miR-132 and miR-145, which are inversely related with mucin 13 expression. Moreover, DEN efficiently binds mucin 13 with high affinity and thus stabilize it as demonstrated by molecular docking analysis. Conclusion: These results suggest that mucin 13 expression is closely associated with hepatocarcinogenesis and could serve as a predictive candidate biomarker for HCC

Mucin 13 expression correlates with tumor development in hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) has a poor prognosis due to ineffective therapeutic modality and lack of early diagnostic marker. Accumulating studies have shown that elevated expression of mucin 13 as potential oncogene and predictive biomarker for various cancer. However, very little is known about its expression and function for development and progression of HCC Objective: To investigate mucin 13 expression in chemically induced hepatocellular carcinoma model. Methodology: Diethyl nitrosamine (DEN) and 2-Acetylaminofluorene (2-AAF) induced method was employed for the development of hepatocellular carcinoma in Male Wistar rats. Serum and tissues were collected at regular interval of time and routinely validated for liver cancer stages. Immunohistochemistry and in situ hybridization were performed on formalin-fixed, paraffin-embedded tissues. Molecular docking studies were performed to study the interaction of mucin 13 and DEN. Results: Our results demonstrate hepatocellular adenoma as observed by histopathological analysis. Biochemical analysis showed a progressive increase in the levels of serum ALT, AST and ALP, suggesting the development and progression of hepatocellular damage. Notably, mucin 13 expression gradually elevated during consecutive stages of hepatocellular carcinoma. Interestingly, an increase in nuclear localization of mucin 13 was observed in treated group as compared to control group. In situ hybridization analysis showed that a decrease in miR-132 and miR-145, which are inversely related with mucin 13 expression. Moreover, DEN efficiently binds mucin 13 with high affinity and thus stabilize it as demonstrated by molecular docking analysis. Conclusion: These results suggest that mucin 13 expression is closely associated with hepatocarcinogenesis and could serve as a predictive candidate biomarker for HCC

Mucin 13 expression is an early indicator of hepatocellular carcinoma development

Background: Hepatocellular carcinoma (HCC) has a poor prognosis due to ineffective therapeutic modality and lack of an early marker for diagnosis. Studies show that increased mucin 13 (MUC13) expression as a possible oncogene and predictive biomarker for various cancers has been shown. But its expression and role in the development of HCC is very little known. Objective: The aim of this study is to investigate the MUC13 expression in chemically induced hepatocellular carcinoma model. Methodology: Male Wistar rats were subjected to a DEN and 2-Acetylaminofluorene (2-AAF) induced method for the development of hepatocellular carcinoma. Serum and tissues were collected at regular intervals and routinely validated for various stages of liver cancer. On formalin-fixed, paraffin-embedded tissues, immunohistochemistry and in situ hybridization were performed. The molecular interaction of mucin 13 and DEN were also performed using in silico analysis. Results: Histopathological analysis of liver tissues revealed the development of hepatocellular carcinoma with successive stages in chemically induced model HCC. Moreover, biochemical analysis showed a progressive increase in serum ALT, AST, and ALP levels, indicating the development and progression of hepatocellular damage. Notably, mucin 13 expression gradually increased during the progression of hepatocellular carcinoma. The treated group showed an increase in nuclear localization of mucin 13 as compared to the control group. In situ hybridization analysis revealed a reduction in miR-132 and miR145, both of which are inversely related to mucin 13 expression. Furthermore, molecular docking analysis showed that DEN efficiently binds mucin 13 with high affinity and thus stabilizes it. Conclusion: These findings suggest that mucin 13 expression is linked to hepatocarcinogenesis and could be used as a candidate biomarker for HCC

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

Role of Nutraceuticals in COVID-19 Mediated Liver Dysfunction.

COVID-19 is known as one of the deadliest pandemics of the century. The rapid spread of this deadly virus at incredible speed has stunned the planet and poses a challenge to global scientific and medical communities. Patients with COVID-19 are at an increased risk of co-morbidities associated with liver dysfunction and injury. Moreover, hepatotoxicity induced by antiviral therapy is gaining importance and is an area of great concern. Currently, alternatives therapies are being sought to mitigate hepatic damage, and there has been growing interest in the research on bioactive phytochemical agents (nutraceuticals) due to their versatility in health benefits reported in various epidemiological studies. Therefore, this review provides information and summarizes the juncture of antiviral, immunomodulatory, and hepatoprotective nutraceuticals that can be useful during the management of COVID-19

Role of Nutraceuticals in COVID-19 Mediated Liver Dysfunction

COVID-19 is known as one of the deadliest pandemics of the century. The rapid spread of this deadly virus at incredible speed has stunned the planet and poses a challenge to global scientific and medical communities. Patients with COVID-19 are at an increased risk of co-morbidities associated with liver dysfunction and injury. Moreover, hepatotoxicity induced by antiviral therapy is gaining importance and is an area of great concern. Currently, alternatives therapies are being sought to mitigate hepatic damage, and there has been growing interest in the research on bioactive phytochemical agents (nutraceuticals) due to their versatility in health benefits reported in various epidemiological studies. Therefore, this review provides information and summarizes the juncture of antiviral, immunomodulatory, and hepatoprotective nutraceuticals that can be useful during the management of COVID-19

Curcumin Nanoformulation for Cervical Cancer Treatment

Cervical cancer is one of the most common cancers among women worldwide. Current standards of care for cervical cancer includes surgery, radiation, and chemotherapy. Conventional chemotherapy fails to elicit therapeutic responses and causes severe systemic toxicity. Thus, developing a natural product based, safe treatment modality would be a highly viable option. Curcumin (CUR) is a well-known natural compound, which exhibits excellent anti-cancer potential by regulating many proliferative, oncogenic, and chemo-resistance associated genes/proteins. However, due to rapid degradation and poor bioavailability, its translational and clinical use has been limited. To improve these clinically relevant parameters, we report a poly(lactic-co-glycolic acid) based curcumin nanoparticle formulation (Nano-CUR). This study demonstrates that in comparison to free CUR, Nano-CUR effectively inhibits cell growth, induces apoptosis, and arrests the cell cycle in cervical cancer cell lines. Nano-CUR treatment modulated entities such as miRNAs, transcription factors, and proteins associated with carcinogenesis. Moreover, Nano-CUR effectively reduced the tumor burden in a pre-clinical orthotopic mouse model of cervical cancer by decreasing oncogenic miRNA-21, suppressing nuclear β-catenin, and abrogating expression of E6/E7 HPV oncoproteins including smoking compound benzo[a]pyrene (BaP) induced E6/E7 and IL-6 expression. These superior pre-clinical data suggest that Nano-CUR may be an effective therapeutic modality for cervical cancer

Reprogramming of pancreatic adenocarcinoma immunosurveillance by a microbial probiotic siderophore

There is increasing evidence suggesting the role of microbiome alterations in relation to pancreatic adenocarcinoma and tumor immune functionality. However, molecular mechanisms of the interplay between microbiome signatures and/or their metabolites in pancreatic tumor immunosurveillance are not well understood. We have identified that a probiotic strain (Lactobacillus casei) derived siderophore (ferrichrome) efficiently reprograms tumor-associated macrophages (TAMs) and increases CD8 + T cell infiltration into tumors that paralleled a marked reduction in tumor burden in a syngeneic mouse model of pancreatic cancer. Interestingly, this altered immune response improved anti-PD-L1 therapy that suggests promise of a novel combination (ferrichrome and immune checkpoint inhibitors) therapy for pancreatic cancer treatment. Mechanistically, ferrichrome induced TAMs polarization via activation of the TLR4 pathway that represses the expression of iron export protein ferroportin (FPN1) in macrophages. This study describes a novel probiotic based molecular mechanism that can effectively induce anti-tumor immunosurveillance and improve immune checkpoint inhibitors therapy response in pancreatic cancer