Inflammatory cascade plays a pivotal role in the onset and progression of major depressive disorder (MDD) and glioblastoma multiforme (GBM). Therefore, questing natural compounds with anti-inflammatory activity such as diosgenin can act as a double-edged sword targeting cancer and cancer-induced inflammation simultaneously. The blood–brain barrier limits the therapeutic efficiency of the drugs against intracranial pathologies including depression and brain cancers. Encapsulating a drug molecule in lipid nanoparticles can overcome this obstacle. The current study has thus investigated the anticancer and antidepressant effect of Tween 80 (P80) coated stearic acid solid lipid nanoparticles (SLNPs) encapsulating the diosgenin. Physio-chemical characterizations of SLNPs were performed to assess their stability, monodispersity, and entrapment efficiency. In vitro cytotoxic analysis of naked and drug encapsulated SLNPs on U-87 cell line indicated diosgenin IC50 value to be 194.4 μM, while diosgenin encapsulation in nanoparticles slightly decreases the toxicity. Antidepressant effects of encapsulated and non-encapsulated diosgenin were comprehensively evaluated in the concanavalin-A–induced sickness behavior mouse model. Behavior test results indicate that diosgenin and diosgenin encapsulated nanoparticles significantly alleviated anxiety-like and depressive behavior. Diosgenin incorporated SLNPs also improved grooming behavior and social interaction as well as showed normal levels of neutrophils and leukocytes with no toxicity indication. In conclusion, diosgenin and diosgenin encapsulated solid lipid nanoparticles proved successful in decreasing in vitro cancer cell proliferation and improving sickness behavioral phenotype and thus merit further exploration.

No abstract

No abstract

Background:Endometriosis is one of the common causes of infertility with very diverse etiology. In modern lifestyle, humans are exposed to several endocrine-disrupting chemicals (EDCs) which may lead to reproductive disturbances. Diethyl hexyl phthalate (DEHP) is one of the common EDCs to which women are exposed by the use of cosmetics, perfumes, food packaging, medicine, and insecticides.Aim:The aim of this study was to measure the levels of DEHP in women diagnosed with endometriosis and healthy females and to compare these levels among different stages of endometriosis.Setting and Design:This descriptive study was conducted at a tertiary care hospital.Subjects and Methods:This study comprised of fifty women diagnosed with endometriosis, aged 20–40 years, and fifty age-matched healthy, fertile women without endometriosis. Females on any medication/comorbid conditions were excluded from the study. Serum DEHP concentrations were measured by high-performance liquid chromatography (HPLC). The results were expressed as means ± standard deviation (SD) (ng/ml of DEHP).Statistical Analysis:Data were analyzed using IBM-SPSS version 20. Two-sample Student's t-test and one-way ANOVA were applied for the analysis.Results:The mean ± SD value of DEHP in cases was 65.29 ± 21.69 ng/ml; however, the mean ± SD value of DEHP in controls was undetectable. Comparison of DEHP among stages of endometriosis revealed an increasing trend with advanced stages (III and IV). The values were not different between the two age groups of women with endometriosis (20–30 and 31–40 years).Conclusion:High levels of DEHP in women diagnosed with endometriosis suggest a role of phthalates in the etiology of endometriosis and permit careful use of such compounds.

Global health estimates indicated approximately 322 million people living with depression. Rising cost of depressive illness treatment and non-responsiveness to existing therapies demand continued research to explore new and more potent therapies. Exploring the potential of natural compounds for their potent antidepressant potentials is becoming topic of interest for scientists. Anti-inflammatory activity of thymoquinone, the active ingredient of Nigella sativa, has been well documented. Current study tested thymoquinone for its antidepressant effect in a Concanavalin A (Con A)induced depressive-like behavior in BALB/c mice. Thymoquinone successfully protected against Con A-induced behavioral despair and anxiety-like behavior. Reduced grooming behavior as a function of Con A treatment, was also reinstated. Underlying mechanism responsible for antidepressant activity of thymoquinone was analyzed by molecular docking. Thymoquinone interacts in halogen-binding pocket (HBP) of serotonin reuptake transporter indicating its potential as serotonin reuptake inhibitor. Results of current study anticipate thymoquinone as a potential antidepressant drug candidate. Practical applications Black seeds of Nigella sativa are consumed with traditional and religious reference since centuries. Thymoquinone, active, and abundant component of Nigella sativa, has shown positive effects in multiple studies against arthritis, asthma, hepatic injury, neurodegeneration, and cancer owing to its immunomodulatory and antiinflammatory attributes. Considering inflammation as one of central components involved in pathophysiology of major depressive disorder, thymoquinone has been evaluated in current study for its antidepressant potential. Positive results of current study propose thymoquinone as an affordable, natural antidepressant drug candidate with better safety profile than currently available antidepressant regimes. Thymoquinone might provide benefits against inflammation-related sickness behavior that is associated with poorer outcome of clinical depression, thus, paving the way for effective drug development against treatment-resistant depression.

Temozolomide (TMZ), the first-line chemotherapeutic drug against glioblastoma multiforme (GBM), often fails to provide the desired clinical outcomes due to inflammation-induced resistance amid inefficient drug delivery across the blood-brain barrier (BBB). The current study utilized solid lipid nanoparticles (SLNPs) for targeted delivery of TMZ against GBM. After successful formulation and characterization of SLNPs and conjugation with TMZ (SLNP-TMZ), their in-vitro anti-cancer efficacy and effect on the migratory potential of cancer cells were evaluated using temozolomide-sensitive (U87-S) as well as TMZ-resistant (U87-R) glioma cell lines. Elevated cytotoxicity and reduction in cell migration in both cell lines were observed with SLNP-TMZ as compared to the free drug (p < 0.05). Similar results were obtained in-vivo using an orthotopic xenograft mouse model (XM-S and XM-R), where a reduction in tumor size was observed with SLNP-TMZ treatment compared to TMZ. Concomitantly, higher concentrations of the drug were found in brain tissue resections of mice treated with SLNP-TMZ as compared to other vital organs than mice treated with free TMZ. Expression of inflammatory markers (Interleukin-1β, Interleukin-6 and Tumor Necrosis factor-α) in a resistant cell line (U87-R) and its respective mouse model (XM-R) were also found to be significantly elevated as compared to the sensitive U87-S cell line and its respective mouse model (XM-S). Thus, the in-vitro and in-vivo results of the study strongly support the potential application of SLNP-TMZ for TMZ-sensitive and resistant GBM therapy, indicatively through inflammatory mechanisms, and thus merit further detailed insights

No abstract

No abstract