Hepato-protective role of itraconazole mediated cytochrome p450 pathway inhibition in liver fibrosis.

Liver is a vital organ and is routinely exposed to toxins. Carbon tetrachloride is one such noxious agent which cause toxicity in liver when CYP450 enzyme bio-activates it. Many hepatoprotective agents are available in market with severe side effects. Appropriate agent is required to combat such liver problems. Azole compounds have much therapeutic values in many diseases. Based upon this fact, present study is aimed to evaluate the repurposing of Itraconazole in the prevention of hepatic fibrosis via inhibition of cytochrome P450 pathway. For in-vitro evaluation of cyto-protective effects in HepG2 cells (untreated and treated groups), cell viability assays, antioxidant evaluation, enzyme linked immunosorbent assay (ELISA) and immunocytochemistry was used. For in-vivo evaluation, CCl4 induced liver fibrotic rat model was used and post treated evaluation was done by blood biochemistry, hematoxylin and eosin (H&E) staining and gene expression profiling. Results of the current study indicated hepatoprotective role of itraconazole via inhibition of CYP450 pathway inhibition. Therefore, Itraconazole use could be a potential therapeutic approach to prevent liver fibrosis.

Biological Significance of EphB4 Expression in Cancer.

Eph receptors and their Eph receptor-interacting (ephrin) ligands comprise a vital cell communication system with several functions. In cancer cells, there was evidence of bilateral Eph receptor signaling with both tumor-suppressing and tumor-promoting actions. As a member of the Eph receptor family, EphB4 has been linked to tumor angiogenesis, growth, and metastasis, which makes it a viable and desirable target for drug development in therapeutic applications. Many investigations have been conducted over the last decade to elucidate the structure and function of EphB4 in association with its ligand ephrinB2 for its involvement in tumorigenesis. Although several EphB4-targeting drugs have been investigated, and some selective inhibitors have been evaluated in clinical trials. This article addresses the structure and function of the EphB4 receptor, analyses its possibility as an anticancer therapeutic target, and summarises knowledge of EphB4 kinase inhibitors. To summarise, EphB4 is a difficult but potential treatment option for cancers.

Sanguinarine Attenuates Lung Cancer Progression via Oxidative Stress-induced Cell Apoptosis.

BACKGROUND: Lung cancer (LC) incidence is rising globally and is reflected as a leading cause of cancer-associated deaths. Lung cancer leads to multistage carcinogenesis with gradually increasing genetic and epigenetic changes. AIMS: Sanguinarine (sang) mediated the anticancer effect in LCC lines by involving the stimulation of reactive oxygen species (ROS), impeding Bcl2, and enhancing Bax and other apoptosis-associated protein Caspase-3, -9, and -PARP, subsequently inhibiting the LC invasion and migration. OBJECTIVE: This study was conducted to investigate the apoptotic rate and mechanism of Sang in human LC cells (LCC) H522 and H1299. METHODS: MTT assay to determine the IC50, cell morphology, and colony formation assay were carried out to show the sanguinarine effect on the LC cell line. Moreover, scratch assay and transwell assay were performed to check the migration. Western blotting and qPCR were done to show its effects on targeted proteins and genes. ELISA was performed to show the VEGF effect after Sanguinarine treatment. Immunofluorescence was done to check the interlocution of the targeted protein. RESULTS: Sang significantly inhibited the growth of LCC lines in both time- and dose-dependent fashions. Flow cytometry examination and Annexin-V labeling determined that Sang increased the apoptotic cell percentage. H522 and H1299 LCC lines treated with Sang showed distinctive characteristics of apoptosis, including morphological changes and DNA fragmentation. CONCLUSION: Sang exhibited anticancer potential in LCC lines and could induce apoptosis and impede the invasion and migration of LCC, emerging as a promising anticancer natural agent in lung cancer management.

Deciphering the Epigenetic Symphony of Cancer: Insights and Epigenetic Therapies Implications.

Epigenetic machinery is a cornerstone in normal cell development, orchestrating tissue-specific gene expression in mammalian cells. Aberrations in this intricate landscape drive substantial changes in gene function, emerging as a linchpin in cancer etiology and progression. While cancer was conventionally perceived as solely a genetic disorder, its contemporary definition encompasses genetic alterations intertwined with disruptive epigenetic abnormalities. This review explores the profound impact of DNA methylation, histone modifications, and noncoding RNAs on fundamental cellular processes. When these pivotal epigenetic mechanisms undergo disruption, they intricately guide the acquisition of the 6 hallmark characteristics of cancer within seemingly normal cells. Leveraging the latest advancements in decoding these epigenetic intricacies holds immense promise, heralding a new era in developing targeted and more efficacious treatment modalities against cancers driven by aberrant epigenetic modifications.

Hypoxia A Typical Target in Human Lung Cancer Therapy.

Lung cancer (LC) is the leading cause of cancer-related death globally. Comprehensive knowledge of the cellular and molecular etiology of LC is perilous for the development of active treatment approaches. Hypoxia in cancer is linked with malignancy, and its phenotype is implicated in the hypoxic reaction, which is being studied as a prospective cancer treatment target. The hypervascularization of the tumor is the main feature of human LC, and hypoxia is a major stimulator of neo-angiogenesis. It was seen that low oxygen levels in human LC are a critical aspect of this lethal illness. However, as there is a considerable body of literature espousing the presumed functional relevance of hypoxia in LC, the direct measurement of oxygen concentration in Human LC is yet to be determined. This narrative review aims to show the importance and as a future target for novel research studies that can lead to the perception of LC therapy in hypoxic malignancies.

In-vitro Augmentation of Mesenchymal Stem Cells by Using Adult Bovine Serum.

BACKGROUND: Umbilical cord mesenchymal stem cells (UC-MSCs) are increasingly being utilized for immune-related disease therapies due to their low immunogenicity. However, the primary culture of UC-MSCs requires the supplementation of serum in the growth medium, which has posed a challenge due to ethical issues related to the collection method of the fetal bovine serum (FBS) that is routinely used in cell culture. AIM: In order to address this, the purpose of this research was to assess the effectiveness of adult bovine serum (ABS) as a different and more affordable source of serum for the in-vitro cultivation of UC-MSCs. UC-MSCs were isolated from the umbilical cord of Wharton's jelly of cow immediately after birth, by digestion with Collagenase type I. METHOD: ABS was collected from fresh bovine sources and heat-inactivated. The morphology of UC-MSCs was observed under an inverted microscope, and growth patterns, proliferative index, and doubling time were calculated every two days to compare the efficacy of ABS with FBS. Immunocytochemistry for specific markers was also conducted on the MSCs. RESULT: The results showed a notable difference in morphology, growth rate, population doubling, and proliferative index between ABS and FBS. CONCLUSION: Intriguingly, ABS proved to be an effective supplement in the growth medium for expanding UC-MSCs in vitro, providing a viable alternative to FBS.

Unveiling the Psychedelic Journey: An Appraisal of Psilocybin as a Profound Antidepressant Therapy.

Depression, a global health concern with significant implications for suicide rates, remains challenging to treat effectively with conventional pharmacological options. The existing pharmaceutical interventions for these illnesses need daily dosing, are accompanied by various adverse effects, and may exhibit limited efficacy in certain cases. However, hope emerges from an unlikely source-Psilocybin, a natural hallucinogen found in certain mushrooms. Recently, this enigmatic compound has garnered attention for its potential therapeutic benefits in addressing various mental health issues, including depression. Psilocybin alters mood, cognition, and perception by acting on a particular subtype of serotonin receptors in the brain. It's feasible that these shifts in consciousness will promote healing development, offering a novel approach to depression management. This comprehensive review explores psilocybin, derived from specific mushrooms, and its implications in the treatment of depression. The study examines new perspectives and therapeutic possibilities surrounding psilocybin, addressing existing gaps in academic literature. It delves into its biosynthesis, unique mechanisms of action, therapeutic applications, and anti-depressive effects. By uncovering the potential of this mind-altering substance, the review aims to advance psychiatric care, offering hope to those globally affected by depression.

In-Vitro Anti-Proliferative, Apoptotic and Antioxidative Activities of Medicinal Herb Kalonji (Nigella sativa).

BACKGROUND: Natural product with apoptotic activity could serve as a potential new source for anti-cancer medicine. Numerous phytochemicals from plants have shown to exert antineoplastic effects via programmed cell death (apoptosis). Cancer is one of the leading causes of death in prosperous countries. The subject study was intended to evaluate the anticancer properties of Kalonji extracts against cancer cell lines HeLa and HepG2 and normal cell lines BHK and VERO were used as normal controls. MATERIALS & METHODS: For the evaluation of anti-proliferative effects, cell viability and cell death in all groups of cells were evaluated via MTT, crystal violet and trypan blue assays. For the evaluation of angiogenesis, Immunocytochemistry and ELISA of VEGF were done. Immunocytochemistry and ELISA of Annexin-V and p53 were performed for the estimation of apoptosis in all groups of cells. Furthermore, LDH assay, antioxidant enzymes activity (GSH, APOX, CAT and SOD) and RT-PCR with proliferative and apoptotic markers along with internal control were also performed. Cancer cells of both cell lines HepG2 and HeLa cells showed reduced viability, angiogenesis and proliferation with increased apoptosis when treated with Kalonji extracts. Whereas anti-oxidative enzymes show enhanced levels in treated cancer cells as compared to untreated ones. CONCLUSION: It was observed that Kalonji extracts have the ability to induce apoptosis and improve the antioxidant status of HeLa and HepG2 cells. They can also inhibit the proliferation and angiogenesis in both these cancer cell lines.