The role of leptin and low testosterone in obesity.

Obesity is a medical condition associated with metabolic disorders and low-grade systemic inflammation. Another characterizing feature of obesity is high circulating levels of leptin (a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate energy balance), a phenomenon termed hyperleptinemia. Hyperleptinemia is associated with both low-grade systemic inflammation and metabolic dysfunction in obese human beings. Moreover, obesity is associated with low testosterone in men, which correlates with high body fat. The association between leptin and low testosterone could potentially be explained via the imbalanced leptin levels that results in higher estrogen levels, which further increases the aromatase activity. The increase in aromatase activity in turn reciprocally inhibits the testosterone levels and hypothalamic pituitary gonadal axis. Novel strategies are being used to treat obesity, including leptin and testosterone therapy. However, the efficacy and adverse effects of these strategies need further validation through preclinical and clinical studies. Additionally, further studies are needed to establish the molecular mechanism behind leptin-modulated changes to testosterone in obese men. This review summarizes the available literature on the role of leptin and low testosterone during obesity.

Neuroblastoma and Stem Cell Therapy: An Updated Review.

Neuroblastoma (NBM) is the second leading pediatric cancer that develops from the precursors of the sympathetic nervous system. To date, surgery, chemotherapy, and radiation serve as the first-line treatment against NBM in high-risk patients. However, few of these approaches have severe side effects. Recently, numerous studies have also reported that high chemotherapy doses, along with stem cell rescue, improvise event-free survival in patients. In this review, the authors attempted to discuss the pathogenesis associated with NBM and how stem cell therapy can be employed for the treatment of NBM. Stem cells are a group of multipotent, undifferentiated cells that are capable of producing all cells in a particular tissue, organ, or organism. They have an endogenous self-renewal property. This property is tightly modulated for the normal homeostasis within the body. However, the failure of this process leads to carcinogenesis, including NBM. As these properties are modulated via various intrinsic as well as extrinsic pathways, the arrest of these pathways via various drugs may help in controlling various carcinomas, including NBM. Recently, stem cells were utilized for the diagnosis and treatment of NBM. Nevertheless, most of the studies conducted to date are mainly designed on bulk-cell analysis, which in turn provides little information about the population of cells. Thus, the authors believe that, by employing single-cell RNA sequencing technologies and computational approaches, we can unmask the tumor heterogeneity in NBM in a more comprehensive way. In the near future, this information will be highly useful for the identification of biomarkers and treatment associated with NBM in humans.

Sulfonate modified Lactoferrin nanoparticles as drug carriers with dual activity against HIV-1.

Intriguing properties and structural dynamics of Lactoferrin have been exploited in numerous applications, including its use as self-assembling, pH sensitive nanoparticles to deliver intended cargo at the disease site. In this study, we explore the possibility of surface modification of Lactoferrin nanoparticles to hone its specificity to target HIV-1 infected cells. Existence of free cysteine groups on Lactoferrin nanoparticles available for reaction with external molecules facilitates conjugation on the surface with Sodium 2-mercaptoethanesulfonate (MES). Conjugation with MES is used to edge a negative charge that can mimic CCR5 and Heparan sulfate (initial point of contact of HIV-1 env to host cell surface) electrostatic charge (Sulfate group). A simple sono-chemical irradiation method was employed for self-assembly of Nanoparticles and for surface modification. The nanoparticles serve dual purpose to abrogate extracellular entry and to target viral enzymes, when loaded with ART drugs. The morphology and size distribution of the formed particles were explored using Transmission Electron Microscope (TEM), Scanning Electron Microscope (SEM) and Dynamic Light Scattering. Raman SERS was employed to understand the difference in the protein upon surface modification. The anti-HIV property of the particles was confirmed in-vitro. The modified device demonstrated acceptable nanoparticle properties with controlled release and higher effective concentration in the area of infection.

Neuroblastoma: An Updated Review on Biology and Treatment.

BACKGROUND: Neuroblastoma (NB) is the second leading extracranial solid tumors of early childhood and clinically characterized by the presence of round, small, monomorphic cells with excess nuclear pigmentation (hyperchromasia).Owing to a lack of definitive treatment against NB and less survival rate in high-risk patients, there is an urgent requirement to understand molecular mechanisms associated with NB in a better way, which in turn can be utilized for developing drugs towards the treatment of NB in human. OBJECTIVES: In this review, an approach was adopted to understand major risk factors, pathophysiology, the molecular mechanism associated with NB, and various therapeutic agents that can serve as drugs towards the treatment of NB in humans. CONCLUSION: Numerous genetic (e.g., MYCN amplification), perinatal, and gestational factors are responsible for developing NB. However, no definite environmental or parental exposures responsible for causing NB have been confirmed to date. Though intensive multimodal treatment approaches, namely, chemotherapy, surgery & radiation, may help in improving the survival rate in children, these approaches have several side effects and do not work efficiently in high-risk patients. However, recent studies suggested that numerous phytochemicals, namely, vincristine, and matrine have a minimal side effect in the human body and may serve as a therapeutic drug during the treatment of NB. Most of these phytochemicals work in a dose-dependent manner and hence must be prescribed very cautiously. The information discussed in the present review will be useful in the drug discovery process as well as treatment and prevention on NB in humans.

Phytochemical profiling and in vitro screening for anticholinesterase, antioxidant, antiglucosidase and neuroprotective effect of three traditional medicinal plants for Alzheimer's Disease and Diabetes Mellitus dual therapy.

BACKGROUND: Extensive epidemiological and clinical studies revealed that Alzheimer's Disease (AD) and Type 2 Diabetes Mellitus (T2D) are most likely to appear simultaneously in aged people as T2D is a major risk factor for AD. Therefore, development of potential multifunctional agents for dual therapy of AD and T2D has received much attention. Buchanania axillaris, Hemidesmus indicus and Rhus mysorensis have been used extensively in popular medicine. The present study was aimed at phytochemical profiling and evaluating multifunctional ability of titled plants in the AD and T2D dual therapy. METHODS: Methanolic extracts and their derived fractions were evaluated for their inhibitory capacities against acetylcholinesterase (AChE) & butyrylcholinesterase (BuChE), and α- & ß-glucosidase besides kinetic analysis of inhibition using methods of Elmann and Shibano, respectively. Antioxidant potency of active fractions was assessed by their DPPH and ABTS radical scavenging activities. Active fractions were tested by the MTT assay to verify cytotoxicity and neuroprotective ability in human nueroblastoma cell lines. Phytochemical screening was done with the aid of spectrophotometric methods. RESULTS: All the methanolic extracts of test plants (BAM, HIM, RMM) showed concentration dependent inhibitory activities against AChE, BuChE, α- and ß-glucosidase enzymes. Subsequent fractionation and evaluation revealed that chloroform fractions BAC, HIC and RMC with IC50 values of 12.29±2.14, 9.94±2.14, 16.65±1.99 and 27.38±1.24; 28.14±0.9, 5.16±0.22, 11.03±0.5 and 87.64±15.41; 41.35±1.6, 15.86±7.3, 26.04±0.37 and 25.33±0.3 were most prominent with regard to inhibition potential against AChE, BuChE, α- and ß-glucosidase, respectively. Kinetic analysis of these active fractions proved that they disclosed mixed-type inhibition against AChE, BuChE, α- and ß-glucosidase enzymes. In the MTT assay, active fractions BAC, HIC, RMC showed significant cell viability at high concentrations (400 µg). Moreover, in MTT assay, the active fractions displayed excellent neuroprotective effects against oxidative stress induced cell death and significant cell viability in SK N SH cells at all concentrations. CONCLUSION: The strong anticholinesterase, antiglucosidase, antioxidant and neuroprotective activities of methanolic extracts and their derived chloroform fractions indicate the potential of Buchanania axillaris, Hemidesmus indicus and Rhus mysorensis as multifunctional therapeutic remedies for the dual therapy of T2D and AD.